Psychosocial factors and medication adherence among recipients of vascularized composite allografts.

OBJECTIVES: Psychosocial factors are important predictors of medication adherence, and subsequently graft survival, in solid organ transplantation. Early experiences suggest this may also be the case in vascularized composite allotransplantation. METHODS: Using validated tools, we surveyed upper extremity transplant recipients at two centers to assess depression (Patient Health Questionnaire-9), personality (Ten-Item Personality Inventory), anxiety (Generalized Anxiety Disorder 7-Item Scale), post-traumatic stress disorder (Primary Care Post-Traumatic Stress Disorder Screen for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition), and social support (Multidimensional Scale of Perceived Social Support). Medication adherence among vascularized composite allotransplantation recipients at two centers was assessed by a member of the clinical research team using the recipients' medical records. RESULTS: Medication adherence was reported for 12 vascularized composite allotransplantation recipients, and 9 vascularized composite allotransplantation recipients completed psychosocial assessments. Most recipients were believed to be adherent to their immunosuppression, however, three recipients were believed to be non-adherent and a member of the clinical team had discussed non-adherence at least once with five recipients. Results from the psychosocial assessment (n = 9) indicated that eight participants had high levels of social support, and eight demonstrated high levels of conscientiousness which have been associated with better medication adherence in solid organ transplantation. However, three participants demonstrated mild anxiety, two demonstrated minimal symptoms of depression, and one demonstrated post-traumatic stress disorder which have been associated with worse medication adherence in solid organ transplantation. CONCLUSION: These findings lay the groundwork for future assessments of the role psychosocial factors play in facilitating medication adherence and broader transplant outcomes.

Evolving ethics, policy and reimbursement issues of vascularized composite allotransplantation: Symposium summary.

In this article, we present a report from a national meeting titled, "Evolving Issues of Vascularized Composite Allotransplantation-A Symposium on Ethics, Policy, and Reimbursement Issues," which convened in September 2017. We discuss the maturation of vascularized composite allotransplantation from an emerging technology to becoming an extension of clinical practice for select patients with complex reconstructive needs. Viewpoints and action items were presented by and discussed among the 70+ clinicians, researchers, policymakers, ethicists, healthcare administrators, and third-party payers who attended the symposium with the goals of implementing a collaborative roadmap for vascularized composite allotransplantation growth, evaluation, and sustainability by establishing a unified plan to help address concerns of the public, policymakers, and healthcare finance. We review the current status of vascularized composite allotransplantation in clinical practice and summarize symposium discussions regarding ethical considerations, reimbursement, payer strategies, and standardization of data collection.

Macroporous nanofiber wraps promote axonal regeneration and functional recovery in nerve repair by limiting fibrosis.

Functional outcomes following nerve repair remain suboptimal. Scarring at the repair site is a major impediment to regeneration. A biomaterial scaffold applied around the coaptation site that decreases inflammation holds great potential in reducing scarring, enhancing axonal growth, and improving functional recovery. In this study, we evaluated the effect of a macroporous nanofiber wrap, comprised of nonwoven electrospun poly-ε-caprolactone (PCL), in improving axonal regeneration in a rat sciatic nerve cut and direct repair model. Controls consisted of conventional epineurial repair. We also evaluated our wrap against the commercially available AxoGuard wrap. At five weeks following repair, the nanofiber wrap group showed a significantly decreased intraneural macrophage invasion and collagen deposition at the repair site. This was associated with increased expression of the anti-inflammatory cytokine (IL-10), decreased expression of the pro-inflammatory cytokine (TNF-α), and a decrease in the M1:M2 macrophage phenotype ratio. These findings suggest that this nanofiber wrap, with its unique macroporosity, is modulating the inflammatory response at the repair site by polarizing macrophages towards a pro-regenerative M2 phenotype. Concomitantly, a higher number of regenerated axons was noted. At sixteen weeks, the nanofiber wrap resulted in enhanced functional recovery as demonstrated by electrophysiology, neuromuscular re-innervation, and muscle histology. When compared to the AxoGuard wrap, the nanofiber wrap showed similar inflammation at the repair site and similar nerve morphometric findings, but there was a trend towards a lower overall number of macrophages invading the wrap wall. These results demonstrate favorable outcomes of the macroporous nanofiber wrap in promoting neuroregeneration and functional recovery following nerve repair. STATEMENT OF SIGNIFICANCE: Electrospun nanofiber scaffolds, with specific fiber and pore sizes, were shown to modulate the immune response and create a regenerative environment. In this paper, we present a macroporous nanofiber wrap, made of poly-ε-caprolactone, to be applied at the coaptation site in primary nerve repair. We show that it regulates the inflammatory response at the repair site and decreases scarring/fibrosis. This results in enhanced axonal regeneration, allowing a higher number of axons to cross the suture line and reach the target muscle in a timely fashion. Functional outcomes are thus improved.

Taming inflammation by targeting cytokine signaling: new perspectives in the induction of transplantation tolerance.

Transplantation tolerance remains an elusive goal, partly due to limitations in our understanding of the interplay between inflammatory mediators and their role in the activation and regulation of T lymphocytes. Although multiple mechanisms acting both centrally and peripherally are responsible for tolerance induction, the signaling pathways leading to activation or regulation of adaptive immunity are often complex, branched, redundant and modulated by the microenvironment's inflammatory milieu. Accumulating evidence clearly indicates that inflammatory cytokines limit the tolerogenic potential of immunomodulatory protocols by supporting priming of the immune system and counteracting regulatory mechanisms, ultimately promoting rejection. In this review, we summarize recent progress in the development of novel therapeutics to manipulate this inflammatory environment and achievements in targeted inhibition of inflammatory cytokine signaling. Ultimately, robust transplant tolerance induction will probably require a multifaceted, holistic approach that integrates the various mechanisms of tolerance induction, incorporates the dynamic alterations in costimulatory requirements of alloreactive T cells, while maintaining endogenous mechanisms of immune regulation.

Clinical implementation of a procedure to prepare bone marrow cells from cadaveric vertebral bodies.

AIMS: Vertebral bone marrow is a rich and easily accessible source of hematopoietic and mesenchymal stem cells that has been used to promote chimerism and transplantation tolerance in connection with cadaveric organ transplantation. The purpose of this study is to provide a detailed account of the procedure used to prepare the first five vertebral bone marrow products for infusion in conjunction with the first hand/hand-forelimb transplants performed at the University of Pittsburgh (PA, USA). MATERIALS & METHODS: The cell separation and release testing were performed at the University of Pittsburgh Cancer Institute's Hematopoietic Stem Cell Laboratory, a Good Manufacturing Practice-compliant facility accredited for clinical cell processing by the Foundation for Accreditation of Cellular Therapy (FACT) and for clinical flow cytometry by the College of American Pathologists (CAP).

Traumatic intratendinous flexor digitorum profundus rupture: A case report.

Intratendinous ruptures of a flexor digitorum profundus tendon are rare in patients who do not have rheumatoid arthritis. A case of a patient with no history of autoimmune disease who suffered a traumatic rupture of the flexor digitorum profundus tendon to the ring finger in the mid-palm is reported.

Les ruptures traumatiques du flexor digitorum profundus intratendineux sont rares chez les patients qui ne souffrent pas de polyarthrite rhumatoïde. On présente ici le cas d'un homme ne présentant aucun antécédent de maladie auto-immune qui a subi une rupture traumatique du flexor digitorum profundus intratendineux de l'annulaire, au niveau du milieu de la paume.