Mardini, Samir

Background Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression. Method A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results. Result Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy. Conclusion Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance.

Background Patients diagnosed with end-stage renal disease (ESRD) are increasing at around 5% annually. Some of these patients will require free tissue transfers to reconstruct their body after trauma or cancer resection. Comorbidities can increase the level of complexity during reconstruction. Aim Our goal is to describe the outcomes of ESRD patients under dialysis who underwent free tissue transfer for head and neck reconstruction. Methods Two cohorts were analyzed: ESRD group on dialysis and a non-ESRD control group after free tissue transfer for head and neck reconstruction. Postoperative complications and mortality were recorded. For coexisting comorbidities, we determine the presence of diabetes mellitus (DM) and peripheral vascular disease (PVD). Results In this study, 85 cases with ESRD on dialysis and 841 controls were analyzed. Most patients were aged ≤ 65 years (82.5%) and nearly 92.9% of them were men. Types of head and neck cancer were neoplasm of other and unspecified parts of the mouth followed by neoplasm of tongue, the gingiva, hypopharynx, and floor of mouth. Patients with ESRD tended to have higher rates of DM and PVD (p < 0.001) and were significantly associated with an increased risk of stroke and increased risk of 30-day mortality. However, there was no significant difference regarding flap failure among groups. Conclusion Despite greater preoperative risk factors, patients with renal failure on hemodialysis do not appear to have a higher rate of free flap failure following head and neck reconstruction. However, other complications can be minimized by optimizing patient's medical condition to succeed with this reconstructive effort.

Severely comminuted fractures of the metatarsal bones with significant bone and soft-tissue loss have commonly subjected patients to proximal amputation procedures. We describe two patients who experienced high-energy traumatic injuries to their limbs that resulted in significant destruction of their first and second metatarsal bones with overlying soft-tissue trauma not amenable to local coverage. In both cases, a vascularized free fibular osteocutaneous flap was used to reconstruct the metatarsal bone defect and traumatized soft tissues so that a proximal amputation was avoided. At an average of 14 months of follow-up, both patients had recovered well and regained independent ambulation, with one patient being able to play soccer. We show that the free fibular osteoseptocutaneous flap is useful in reconstructing significant metatarsal bone defects and in avoiding amputations in this patient population. The skin component of the flap may be used to fill soft-tissue losses, and the fibula bone may be osteotomized so that more than one ray may be reconstructed. (J Am Podiatr Med Assoc 101(6): 531–536, 2011)