The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago. Subsequently, the liver’s role in multivisceral transplantation was recognized, as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart. The liver has a unique architecture and is home to many cells involved in immunity and inflammation. After transplantation, these cells migrate from the liver into the recipient. Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system. Recent studies on human T-cell subtypes, cytokine expression, and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation. In this article, we discuss the privileged state of liver transplantation compared to other solid organ transplantation, the liver allograft’s role in multivisceral transplantation, various cells in the liver involved in immune responses, and the potential mechanisms underlying immunomodulation of host alloresponses.
Objective:The objective of this study was to evaluate the feasibility of a computer based stent registry with patient directed automated information system to prevent retained double J stents.Materials and Methods:A stent registry system was developed in collaboration with our Computerized Hospital Information Processing Service Department. This computer based stent registry with patient directed automated information system was integrated with the existing clinical work station. We reviewed the records retrospectively and assessed the feasibility of the system in reminding clinicians and patients regarding the stent and its date of removal.Results:In a short run at our department, this new system appeared feasible, with patients promptly responding to the short message service and letter alerts.Conclusions:Computer based stent registry with patient directed automated information system is feasible in a clinical setting. A prospective study is needed for evaluation of its efficacy in preventing retained stents.
The liver is an immunologically active organ with a tolerogenic microenvironment at a quiescent state. The immunoregulatory properties of the liver appear to be retained after transplantation because liver allografts can reduce alloresponses against other organs that are simultaneously transplanted. Mechanisms of this phenomenon remain unknown. Given the known immunomodulatory properties of mesenchymal stromal cells (MSCs), we hypothesized that liver mesenchymal stromal cells (L‐MSCs) are superior immunomodulators and contribute to liver‐mediated tolerance. L‐MSCs, generated from human liver allograft biopsies, were compared with adipose mesenchymal stromal cells (A‐MSCs) and bone marrow mesenchymal stromal cells (BM‐MSCs). Trilineage differentiation of L‐MSCs was confirmed by immunohistochemistry. Comparative phenotypic analyses were done by flow cytometry and transcriptome analyses by RNA sequencing in unaltered cell cultures. The in vitro functional analyses were performed using alloreactive T cell proliferation assays. The transcriptome analysis showed that the L‐MSCs are different than the A‐MSCs and BM‐MSCs, with significant enrichment of genes and gene sets associated with immunoregulation. Compared with the others, L‐MSCs were found to express higher cell surface levels of several select immunomodulatory molecules. L‐MSCs (versus A‐MSCs/BM‐MSCs) inhibited alloreactive T cell proliferation (22.7% versus 56.4%/58.7%, respectively; P < 0.05) and reduced the frequency of interferon ɤ–producing T cells better than other MSCs (52.8% versus 94.4%/155.4%; P < 0.05). The antiproliferative impact of L‐MSCs was not dependent on cell‐to‐cell contact, could be reversed incompletely by blocking programmed death ligand 1, and required a higher concentration of the competitive inhibitor of indoleamine 2,3‐dioxygenase for complete reversal. In conclusion, L‐MSCs appear to be uniquely well‐equipped immunomodulatory cells, and they are more potent than A‐MSCs and BM‐MSCs in that capacity, which suggests that they may contribute to liver‐induced systemic tolerance.
The incidence of varicocele in the general population is up to 15%. It is estimated that the prevalence of pain with varicoceles is around 2-10%. Till the year 2000, only two studies evaluated efficacy of varicocelectomy in painful varicoceles with conflicting results. Over the past decade many other studies have addressed this issue and reported on the treatment outcome and predictors of success. We critically appraised studies published from March 2000 to May 2013 evaluating surgical management in painful varicoceles to provide an evidence based review of effectiveness of varicocelectomy in relieving pain in patients with symptomatic painful varicoceles. The association between varicoceles and pain is not clearly established. Conservative treatment is warranted as the first line of treatment in men with painful clinical varicoceles. In carefully selected men with clinically palpable varicoceles and associated characteristic chronic dull ache, dragging or throbbing pain who do not respond to conservative therapy, varicocelectomy is warranted and is associated with approximately 80% success. However, surgical success does not always translate into resolution of pain and pain might persist even when no varicoceles are detected postoperatively.
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