Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation.

Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA. Methods: For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods. Results: In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times. Discussion: Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts.

A brief survey on prescriber beliefs regarding compounded topical pain medications.

Pain is extremely common in the U.S. It is estimated that 116 million Americans suffer from chronic pain. Narcotics and opioid medications are heavily relied upon for the treatment of pain. Currently, there is an epidemic of opioid abuse and misuse in the U.S. and alternative methods for the treatment of pain are required. Topical compounded pain creams are thought to be one such alternative. The purpose of this study was to establish a baseline regarding the beliefs of community physicians on the safety and efficacy of these compounds. A survey was sent to practicing physicians in the U.S. regarding their prescribing behaviors for topical compounds, as well as their beliefs about the efficacy and safety of these medications. Eleven prescribing practitioners participated in this survey with a response rate of 78%. The results were compiled with basic statistical work (Excel). This survey demonstrated that at the time of the study, topical compound creams for the treatment of pain were commonly used in clinical practice; these creams were used for musculoskeletal pain and for neuropathic pain. It was also determined that the vast majority of practicing prescribers felt that compounded pain creams were more efficacious than mass-produced, U.S. Food and Drug Administration-approved creams marketed by large multi-national pharmaceutical companies. Most of the respondents felt that these compounds allowed them to reduce their narcotic prescriptions overall. In addition, the results demonstrated that the prescribers felt these compounds were safe for their patients. In this small survey of practicing prescribing providers regarding the use of topical compounds, we found that these medications were not only effective but also safe.

Radiographic spectrum of severity in Madelung's deformity.

PURPOSE: To establish whether Madelung's deformity demonstrates a radiographic continuum of severity and whether a forme fruste does exist. METHODS: Ulnar tilt, lunate subsidence, palmar carpal displacement, and lunate fossa angle were measured in 81 wrist radiographs with obvious or suspected Madelung's deformity. Statistical analyses based on these measurements were performed to ascertain if there is a deformity continuum. RESULTS: Ranges of 15 degrees to 51 degrees (mean, 28 degrees) for ulnar tilt, -7 to +11 mm (mean, -0.8 mm) for lunate subsidence, 9 to 25 mm (mean, 15.3 mm) for palmar carpal displacement, and 20 degrees to 56 degrees (mean, 33 degrees) for lunate fossa angle were obtained. Significant correlations were observed between all measurements. CONCLUSIONS: Madelung's deformity encompasses a spectrum of radiographic abnormality. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic I.