Faculty Bibliography

Targeted muscle reinnervation (TMR) is a procedure in which amputated nerves are transferred to motor branches of functionally expendable muscles, which can then serve as "biological amplifiers" of neurologic information. It is a technique that was developed with the primary intent of improving myoelectric prosthesis control in high level upper extremity amputees. Over time, TMR has been shown to confer significant benefits in terms of both residual and phantom limb pain and as such has become a powerful tool in neuroma management in amputees and non-amputees. This review first discusses general principles of amputation management in the upper extremity, including the different types of prosthetics that are available for these patients. The history, rationale, and evolution of TMR will then be outlined, followed by several relevant surgical principles. Finally, the current evidence for and against TMR will be reviewed. Robust data on the functional benefits are still needed, and future studies will continue to clarify its role in both upper and lower extremity amputees.

Background/UNASSIGNED:The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of understanding the underlying conditions that lead to COVID-19. Oral health has systemic implications in the maintenance of a healthy state. This study aimed to summarize evidence on the prevalence of oral health conditions in participants with COVID-19 and assess the associations between oral health conditions and COVID-19 related outcomes. Methods/UNASSIGNED:Article searches were conducted in five databases and the gray literature from December 1, 2019 to March 1, 2021. Studies that reported oral health conditions for participants with COVID-19 and/or examined associations between oral health and COVID-19 were included. Results/UNASSIGNED:We identified 15 articles that encompassed 5,377 participants with COVID-19 from 10 countries. Dry mouth was the most common oral health condition reported (41.0%), followed by oral lesions (38.8%), orofacial pain (18.3%), and periodontal symptoms (11.7%). Based on the pooled odds ratios (ORs), periodontal symptoms were not associated with COVID-19 positivity (OR = 1.1; 95% confidence intervals [CI], 0.73-1.65) or mortality (OR = 2.71; 95% CI, 0.64-11.51), but were associated with COVID-19 severity (OR = 3.18; 95% CI, 1.81-5.58). Conclusions/UNASSIGNED:Oral health conditions are common in participants with COVID-19 and should be considered in both the onset and progression of this disease. Knowledge in this area is still limited, and the quality of the data extracted was low. Further longitudinal studies are needed to ascertain whether oral health conditions are a consequence of infection with SARS-CoV-2 or whether they predate infection and are risk factors for COVID-19.

The first digital replantation was performed over 50 years ago, and soon after surgeons in countries around the world were finding great success in their outcomes. The initial wave of success, however, has been followed by somewhat disappointing results in the United States in recent years. The steadily declining number of attempts at replantation and diminishing viability rates can be attributed to several factors, many of which can be addressed with centralization of care and the modification of our own indications and contraindications. While other regions of the world still enjoy good outcomes, the United States must make a concerted effort to improve their results for these devastating injuries.

OBJECTIVES/OBJECTIVE:Salivary hypofunction and xerostomia, are common side effects of radiotherapy, negatively impacting quality of life. The OraRad study presents results on the longitudinal impact of radiotherapy on salivary flow and patient-reported outcomes. PATIENTS AND METHODS/METHODS:Prospective, multicenter cohort study of 572 patients receiving curative-intent head and neck radiotherapy (RT). Stimulated salivary flow (SSF) rate and patient-reported outcomes were measured prior to RT and at 6- and 18-months post-RT. Linear mixed effects models examined the relationship between RT dose and change in salivary flow, and change in patient-reported outcomes. RESULTS:544 patients had baseline salivary flow measurement, with median (IQR) stimulated flow rate of 0.975 (0.648, 1.417) g/min. Average RT dose to parotid glands was associated with change in salivary flow post-RT (p < 0.001). Diminished flow to 37% of pre-RT level was observed at 6 months (median: 0.358, IQR: 0.188 to 0.640 g/min, n = 481) with partial recovery to 59% of pre-RT at 18 months (median: 0.575, IQR: 0.338 to 0.884 g/min, n = 422). Significant improvement in patient-reported swallowing, senses (taste and smell), mouth opening, dry mouth, and sticky saliva (p-values < 0.03) were observed between 6 and 18 months post-RT. Changes in swallowing, mouth opening, dry mouth, and sticky saliva were significantly associated with changes in salivary flow from baseline (p-values < 0.04). CONCLUSION/CONCLUSIONS:Salivary flow and patient-reported outcomes decreased as a result of RT, but demonstrated partial recovery during follow-up. Continued efforts are needed to improve post-RT salivary function to support quality of life.

G protein-coupled receptors (GPCRs) regulate many pathophysiological processes and are major therapeutic targets. The impact of disease on the subcellular distribution and function of GPCRs is poorly understood. We investigated trafficking and signaling of protease-activated receptor 2 (PAR₂) in colitis. To localize PAR₂ and assess redistribution during disease, we generated knockin mice expressing PAR₂ fused to monomeric ultrastable green fluorescent protein (muGFP). PAR₂-muGFP signaled and trafficked normally. PAR₂ messenger RNA was detected at similar levels in Par₂-mugfp and wild-type mice. Immunostaining with a GFP antibody and RNAScope in situ hybridization using F2rl1 (PAR₂) and Gfp probes revealed that PAR₂-muGFP was expressed in epithelial cells of the small and large intestine and in subsets of enteric and dorsal root ganglia neurons. In healthy mice, PAR₂-muGFP was prominently localized to the basolateral membrane of colonocytes. In mice with colitis, PAR₂-muGFP was depleted from the plasma membrane of colonocytes and redistributed to early endosomes, consistent with generation of proinflammatory proteases that activate PAR₂ PAR₂ agonists stimulated endocytosis of PAR₂ and recruitment of Gα_q, Gα_i, and β-arrestin to early endosomes of T84 colon carcinoma cells. PAR₂ agonists increased paracellular permeability of colonic epithelial cells, induced colonic inflammation and hyperalgesia in mice, and stimulated proinflammatory cytokine release from segments of human colon. Knockdown of dynamin-2 (Dnm2), the major colonocyte isoform, and Dnm inhibition attenuated PAR₂ endocytosis, signaling complex assembly and colonic inflammation and hyperalgesia. Thus, PAR₂ endocytosis sustains protease-evoked inflammation and nociception and PAR₂ in endosomes is a potential therapeutic target for colitis.

Efficacy of monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (calcitonin receptor-like receptor/receptor activity modifying protein-1, CLR/RAMP1) implicates peripherally-released CGRP in migraine pain. However, the site and mechanism of CGRP-evoked peripheral pain remain unclear. By cell-selective RAMP1 gene deletion, we reveal that CGRP released from mouse cutaneous trigeminal fibers targets CLR/RAMP1 on surrounding Schwann cells to evoke periorbital mechanical allodynia. CLR/RAMP1 activation in human and mouse Schwann cells generates long-lasting signals from endosomes that evoke cAMP-dependent formation of NO. NO, by gating Schwann cell transient receptor potential ankyrin 1 (TRPA1), releases ROS, which in a feed-forward manner sustain allodynia via nociceptor TRPA1. When encapsulated into nanoparticles that release cargo in acidified endosomes, a CLR/RAMP1 antagonist provides superior inhibition of CGRP signaling and allodynia in mice. Our data suggest that the CGRP-mediated neuronal/Schwann cell pathway mediates allodynia associated with neurogenic inflammation, contributing to the algesic action of CGRP in mice.

SUMMARY/CONCLUSIONS:As the field of plastic surgery continues to advance, so too do the number and complexity of ethical challenges faced by plastic surgeons. There is a paucity of literature, however, focusing on ethics in plastic surgery. Therefore, the authors offer a timely special topic series discussing ethical issues relevant to the field of plastic surgery. The goals of this series are four-fold: (1) to increase awareness of both frequently and less commonly encountered ethical issues in plastic surgery, (2) to foster discussion and debate of relevant and significant ethical issues, (3) to facilitate clinical ethics education and scholarship in plastic surgery, and (4) to apply an understanding and analysis of ethical issues in a way that optimizes clinical decision-making and delivery of patient care. In this introductory article, the authors discuss the current state of medical ethics scholarship in plastic surgery and introduce the first of several topics that will be detailed in the series. Ultimately, the hope is that increased awareness of the ethical challenges faced by surgeons and patients will improve the practice of plastic surgery.