The 2019 Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference was conducted in Rosemont, Illinois from April 26 to 28. The symposium addressed several exciting topics, including the state of the art in facial transplantation, advances in imaging for oral and maxillofacial surgery, diseases of immune function, wound healing, and surgeon wellness and longevity. Samir Mardini, MD, Plastic and Reconstructive Surgeon from the Mayo Clinic, Rochester, MN, shared his experience with facial transplantation. The indications for facial transplantation included the treatment of trauma, gunshot wounds, chemical burns, neurofibromatosis, and large ablative defects. The preparation for facial transplantation is exhaustive, with a myriad of ethical issues to be considered. In addition, preparing for the technical aspects of the transplantation requires hundreds of hours of cadaver dissections completed with all team members. It is not unusual to have multiple teams with dedicated responsibilities. Surgical sequencing during the transplantation is critical. Preparation and harvesting of the donor should be completed initially. If donor harvesting is progressing well, preparation of the recipient can begin with soft tissue, followed by the necessary osteotomies. Reconstruction of the sphincters of the face is critical to provide functionality. This requires the integrity of the proximal portion of the recipient's facial nerve. Sensation can also be restored if the divisions of the trigeminal nerve are repaired. The technical aspects of facial transplantation dictates that both the donor and the recipient have computed tomography (CT) scans available such that virtual surgery planning can be completed on both, with the construction of surgical guides and templates to translate the virtual plan to the operating room. Multiple intraoperative photographs should be taken to help identify and label the anatomic structures for reconstruction. After insetting of the skeletal structures and soft tissues, microsurgical repair begins with the facial vessels, followed by the facial, infraorbital, and inferior alveolar nerves. A free vascularized donor skin flap (based on the tibial artery) is inset into the groin of the recipient to serve as an accessible biopsy site to monitor rejection. The total surgery time can approach 20 hours for donor harvesting and 30 hours for recipient insetting. Anil Chandraker, MD, a renal transplant researcher from Brigham and Women's Hospital, Boston, MA, discussed how acute rejection rates have decreased with the use of induction therapy, better human leukocyte antigen matching and stronger maintenance and immunosuppression. The goals of immunosuppressive therapy are to reduce acute rejection, nephrotoxicity, generalized side effects, and overimmunosuppression. The current approaches to immunosuppression for organ transplantation involve the use of induction drugs, maintenance drugs, and antirejection drugs. Induction drugs (eg, OKT3–anti-CD3, basiliximab, antithymocyte globulin, alemtuzumab) are used to prevent the initial immune response during the critical early post-transplant period, which can trigger acute rejection and delay graft function. Also, induction can allow for a lower overall intensity of maintenance immunosuppression. The use of induction therapy has led to decreased rates of acute rejection, which has been strongly correlated with long-term allograft outcomes. Maintenance drugs will be required for life and have included steroids, calcineurin inhibitors (ie, cyclosporine, tacrolimus), antiproliferative drugs (ie, azathioprine, mycophenolate), and mammalian target of rapamycin inhibitors (ie, sirolimus, everolimus). Antirejection drugs are used to treat acute rejection and include rituximab, leflunomide, belatacept, bortezomib, eculizumab, intravenous immunoglobulin, and plasmapheresis. Patients with highly sensitized immune systems (eg, previous transplantation, multiple transplanted organs) have an increased risk of rejection. Recipients who are African American or Hispanic and those receiving ABO-incompatible organs will also have a greater risk of rejection and will require modified immunosuppressive regimens. The standards for immunosuppression still vary widely throughout transplant centers. Most protocols now use both induction and maintenance phases, which have improved outcomes. An impediment to the development of new medications has been the difficulty with showing improvement in the outcomes within a short time period. Branden Parent, JD, from the New York University School of Professional Studies, New York, NY, provided insight into the many challenging ethical issues associated with facial transplantation. The main goal of facial transplantation is to increase the function of the recipient and diminish social isolation. Facial transplantation has many unique ethical issues. Although many individuals are registered organ donors, most have not specified facial tissues. Thus, family consent must be obtained for individuals in nearly all cases. For the recipient, receiving a facial transplant is not considered a lifesaving procedure. Although subjects can recover from “social death,” the procedure is complicated, and the risk of rejection is considerable and could result in worsening of the facial defect. The need for lifelong immunosuppressive therapy could also actually reduce the life expectancy of the recipient. Additionally, the cost of the facial transplantation (>$1 million) far exceeds that of other organ transplantations and places a significant financial burden on the hospital. Yet another consideration is the loss of privacy for the recipient and staff involved in the transplant. Considerable support is needed for the recipient to help manage the exposure and loss of anonymity. At present, the selection criteria for identifying a potential recipient have not been well defined. This is in contrast to the criteria for other organ transplantations, which have clear objective parameters to stratify potential recipients. Additional outcomes research is needed to improve the chances for long-term success and potential third-party funding for facial transplantation. Avneesh Chhabra, MD, Associate Professor of Radiology, Department of Radiology and Orthopedic Surgery, and Chief of Musculoskeletal Radiology, University of Texas Southwestern Medical Center, Dallas, TX, discussed the principles and techniques for magnetic resonance neurography (MRN) for injuries of the trigeminal nerve. Previous magnetic resonance imaging (MRI) did not allow for visualization of small peripheral nerves such as the trigeminal nerve. Thick slices, suboptimal fat saturation, and low-field scanners were prohibitive. Previous MRI studies provided no insight into the internal architecture of the nerves and could not provide a diagnosis after nerve injury. MRN represents an advance in imaging that allows for the visualization of peripheral nerves. MRN is multiplanar imaging technique dedicated to enhancing peripheral nerve visualization using a 3 Tesla magnet. Three-dimensional (3D) diffusion weighted imaging and diffusion tensor imaging result in high resolution and uniform fat suppression. This allows for the detection of endoneurial fluid, intraneural edema, and mass lesions. Altered diffusion characteristics correlate with axonal degeneration and regeneration. Abnormal nerves will have focal or diffuse enlargement and will lack distal tapering. They will have T2-weighted hyperintensity and could show loss of the fascicular pattern. They will often have focal or diffuse deviation and can have discontinuity or a neuroma in continuity. The perineural fat will often be effaced or distorted. The extent of these alterations in the trigeminal nerve have been shown to be associated with neurosensory testing (NST), surgical findings, and prognosis. John Zuniga, DDS, MS, PhD, Professor of Oral and Maxillofacial Surgery, the Departments of Surgery and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, presented on the correlation among MRN, clinical NST, the Sunderland classification, and the surgically visualized nerve injury. Clinical NST remains the reference standard for the diagnosis of inferior alveolar and lingual nerve injuries. The disadvantages of NST include delaying treatment of the injury and over- or underestimation of the level of injury. In addition, NST cannot adequately delineate the anatomy and location of the injury. MRN has improved the ability to assess patients with suspected trigeminal nerve injuries. With the currently available 3-dimensional (3D) steady-state and diffusion-based techniques, better T2-weighted evaluation of the trigeminal nerve has become possible. After tooth extraction injuries, MRN has been shown to have moderate to strong correlations with Medical Research Council scale scoring and surgical findings. MRN also allows for mapping of the trigeminal injury and can stratify injuries into traumatic and nontraumatic conditions. Mel Mupparapu, DMD, Professor of Oral and Maxillofacial Radiology and Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, presented a report on nuclear medicine and maxillofacial inflammatory disease. The use of radioisotopes in nuclear medicine allows for the ability to detect pathologic changes in cellular activity long before structural changes can be seen on CT or MRI. Multiple radioisotopes are available, with the ultimate choice depending on the disease being investigated. The radioisotopes are administered intravenously and preferentially taken up by certain tissues, depending on which isotope has been chosen. The isotope then releases positrons that strike electrons in the tissue, resulting in the generation of gamma rays (photons) that can be measured using a scintillation gamma ray detector during positron emission tomography (PET). The commonly used isotopes include 18F-fluorodeoxyglucose, technetium-99 methylene diphosphonate (99mTc), and gallium-67. The combination of PET scanning with CT or MRI allows for better delineation of the disease and greatly improves the specificity. The most common indications for nuclear medicine in oral and maxillofacial surgery include head and neck cancer, osteomyelitis, medication-related osteonecrosis of the jaw, inflammatory arthropathy, and condylar hyperplasia. Rom S. Leidner, MD, a hematologist/oncologist at Providence Cancer Institute, Portland, OR, presented a report on the increasing role of immunotherapy for oral cancer. Immunotherapy for head and neck cancer was approved in 2016 by the Food and Drug Administration and has shown great promise in increasing patient survival. Immunotherapies are designed to enable the immune system to eliminate cancer cells. Cancer cells tend to avoid the immune system by avoiding immune checkpoint pathways as a result of certain cancer-specific proteins (eg, programmed cell death protein 1 [PD-1] and programmed cell death ligand 1 [PD-L1]). Immune checkpoint inhibitors (anti–PD-1 and anti–PD-L1 monoclonal antibodies) block this inhibition to enhance the patient's immune response to the cancer. Additionally, OX40, a member of the tumor necrosis factor (TNF) receptor family can enhance T-cell memory, proliferation, and antitumor activity in patients with metastatic cancer. Immunotherapy can be given as adjuvant or neoadjuvant to surgical treatment and has not been associated with wound healing complications. Furthermore, immunotherapies might have a synergistic role with surgery of head and neck squamous cell carcinoma. Bonnie Padwa, DMD, MD, Boston Children's Hospital, Boston, MA, presented an update on pediatric chronic nonbacterial osteomyelitis (CNO) of the jaw. CNO is a poorly understood, sterile inflammatory osteitis that occurs in children. Although it is most common in the metaphyseal plates of the long bones, it can occur in any bone, including the mandible, and can be isolated or multifocal. The mandible has been the bone most commonly affected in unifocal disease. Chronic recurrent multifocal osteomyelitis (CRMO) is the term used to describe multifocal disease often associated with extraosseous inflammatory disease and can include the skin, eyes, lungs, or gastrointestinal tract. CRMO has been associated with autoimmune diseases such as Crohn's disease and seronegative spondyloarthropathy and might represent the pediatric counterpart to SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. The median age at the diagnosis of CNO has been 9 years (range, 2 to 22), and CNO has more commonly affected girls (male/female ratio, 1.5 to 2.1:1). CNO has an insidious onset of bone pain, which can be associated with localized swelling, warmth, and tenderness. The pain will often be worse at night and does not have associated constitutional symptoms. It can be associated with other inflammatory conditions and could have a familial component, with 50% of patients having a first- or second-degree relative with an inflammatory condition. Although an infectious etiology has long been suspected, the results from culture and microbial studies have been consistently negative. Although CNO might not be detected on plain radiographs in the early phases, CT has shown better sensitivity in detecting the radiolucent, osteolytic, or sclerotic lesions, which will vary by disease stage. In general, CNO will result in expansion of the mandible, with a periosteal reaction that is smooth and lamellated but differs in appearance from that of neoplastic disease and fibrous dysplasia. Although children will usually have unifocal disease at presentation, 93% will subsequently develop disease at another site within 4 years. Whole body imaging (eg, MRI or 99mTc-labeled scintigraphy) should be considered at the diagnosis to rule out the presence of asymptomatic bone lesions. MRI with gadolinium enhancement will show a high-signal intensity of the bone marrow on fat-saturated T1-weighted images. During remission, the radiographic findings can persist, making the specificity of the imaging modalities problematic. The erythrocyte sedimentation rate and C-reactive protein levels will often remain negative but can increase to greater than the normal range with disease flares. If the diagnosis remains unclear, an extraoral (to avoid contamination by oral flora) biopsy with an adequate cortical and cancellous bone specimen can be obtained. CNO should be considered a rheumatologic disease, and a rheumatology referral is recommended if CNO is suspected. Treatment should be directed toward reducing pain and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered first-line treatment. Persistent pain after 3 months of treatment requires consideration for second-line agents such as methotrexate, TNF-α inhibitors, and/or bisphosphonates. Disease can persist despite treatment, and the rate of recurrence after initially successful treatment has approached 80%. Matthew Stoll, MD, Rheumatologist from the University of Alabama, Birmingham, Birmingham, AL, provided an update on the diagnosis and management of temporomandibular joint (TMJ) arthritis in children with juvenile idiopathic arthritis (JIA). JIA is characterized by synovial inflammation and destruction of the joint soft and osseous tissues. Single or multiple joints can be affected, and the classification will be determined by the number of joints involved and the presence of systemic or extra-articular features. Patients with all types of JIA have a risk of TMJ arthritis, which affects 50 to 80% of children with JIA. Early TMJ arthritis can be clinically silent; however, long-term damage can occur, leading to cosmetic alterations, difficulty in chewing, and obstructive sleep apnea. The end-stage findings can include retrognathia, facial asymmetry, malocclusion, and limited jaw motion. Imaging studies are indicated for the diagnosis and monitoring of TMJ arthritis. Skeletal abnormalities might not be evident early in the disease process on plain radiographs. However, condylar erosion or flattening and/or joint space narrowing can occur over time. MRI with intravenous gadolinium enhancement has generally been considered the reference standard screening modality for the detection of active arthritis. Treatment of JIA requires multiple therapies, including NSAIDs, disease-modifying antirheumatic drugs, and/or biologic drugs such as TNF-α inhibitors. Advances in medical therapy have resulted in the potential for a profound effect on children with JIA. The TMJ might be different, however, because nearly one half (49%) of patients with otherwise inactive JIA will have MRI evidence of TMJ arthritis. Systemic treatment of JIA remains the initial management for patients. Intra-articular corticosteroid injections (IACIs) have long been used for management of mono-arthritis or in conjunction with systemic therapy. IACIs have a long track record of safety and effectiveness in joints, including the TMJ; however, the potential for impaired growth and heterotopic bone formation should be considered. Other promising options for local therapy included iontophoresis, infliximab injections, and arthrocentesis. George Muschler, MD, from the Orthopedic and Rheumatological Institute, Cleveland Clinic, Cleveland, OH, discussed quantitative strategies for cellular therapies with musculoskeletal applications. Stem cell biology is becoming more mainstream and commercially available, with nearly 700 stem cell clinics opening in the United States. The predominant use for stem cells has been in orthopedic surgery. Adult stem cell sources include bone, bone marrow, fat, synovium, periosteum, muscle, and blood. Platelet preparations, such as platelet-rich plasma (PRP), can provide stem cells but this has been inconsistent. The number of stem cells can vary among patients, the device used, and the nature of the preparation. The basic tenet behind the use of PRP assumes that stem cells, progenitor cells, and platelets will survive and proliferate, resulting in repair and revascularization, immunomodulation, and the release of growth factors, such as transforming growth factor-β and vascular endothelial growth factor (VEGF). Quantitative strategies have been implemented to improve the quantity and consistency between samples of stem cells. These have included magnetic separation, in vitro expansion through adherent culture-expanded cells, and performance-based selection. Performance-based selection has been shown to be the most effective in identifying appropriate stem cells for therapy. This has been accomplished through automated cell and colony management using a process of selection, expansion, and correction. Many commercial products have claimed to have stem cells within them; however, the actual number of stem cells present has often been limited. Stem cell therapies are more expensive than PRP therapies but have not provided increased efficacy. Despite the lack of scientific evidence, the marketing and commercialization of “stem cell” injection therapies have continued. The hype in social media has increased the appeal of these stem cell therapies through misleading or false claims. These have included posts that have failed to provide a balanced discussion on the risks, benefits, and limitations of stem cell therapy. An urgent need exists for better education, Food and Drug Administration and Federal Trade commission enforcement, nomenclature standards, product standards, reporting standards, and clinical trials of stem cell therapies. Stephen Feinberg, DDS, from the University of Michigan, Ann Arbor, MI, presented a report on tissue engineering of human oral mucosa and its role in wound healing and reconstructive surgery. The function of the oral epithelium is to provide a protective covering that actively responds to the environment, participates in innate immunity (β-defensins), and signals (X-talk) underlying tissues and cells. The potential uses of autogenous ex vivo-produced oral mucosa include reconstruction, gene therapy, and wound healing. These include delivery of growth factors, prevention of oral cancer recurrence, drug delivery systems, and enhanced wound healing. Human tissue-engineered “ex vivo produced oral mucosa equivalent” (EVPOME) has been developed and shown to secrete VEGF in vitro that peaks at day 11 and correlates with epithelial healing. Developing EVPOME was based on the use of oral keratinocytes, which are easily obtainable and readily expandable and have a high degree of inherent vascularity. Compared with skin keratinocytes, oral keratinocytes migrate 2 to 3 times faster, have a greater proliferative capacity, and heal faster in inflamed environments. Phase I clinical trials of EVPOME have shown its safety for intraoral use and the ability to augment keratinized tissue around teeth. A phase IIA clinical trial of EPVOME to determine the efficacy around teeth and implants is pending. Future trials could also involve the use of EVPOME with composite grafts and designer microvascular-free flaps for lip reconstruction. Microvascular prelaminated flaps will allow for immediate perfusion directly into the muscle and allow for reconstruction of lips with appropriate function. Microvascular grafts could also be inset within other muscle tissue such as the latissimus dorsi, resulting in the growth of a functional construct with muscle, vessels, and nerves that could be harvested once healed and set into the defect site to allow for lip reconstruction. A similar approach for anal and vaginal reconstruction has been adopted by the US Department of Defense. The use of oral keratinocytes in burn management has also been investigated. The advantage of the use of oral keratinocytes is that they secrete proangiogenic cytokines, secrete innate antimicrobial agents (β-defensins), live in an environment full of bacteria and fluid (similar to a burn), have a greater growth rate and division compared with skin keratinocytes, maintain biological activity longer than skin cells, and do not produce scarring. Sandeep Kathju, MD, from the McGowan Institute of Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, discussed the phases of wound healing and compared cutaneous and intraoral wound healing. Oral keratinocytes provide for improved healing with minimized scarring compared with cutaneous scarring. Factors affecting oral wound healing include the moist environment, a vastly greater microbial challenge, repeated mechanical and chemical provocation, and the need to heal quickly to allow for the intake of nutrition. Although both oral and cutaneous wound healing have hemostatic, inflammatory, proliferative, and remodeling phases, oral wound healing proceeds through these phases more rapidly. Oral wound healing has faster epithelization and less inflammation, angiogenesis, and scar formation. The presence of saliva in oral healing appears to be advantageous. The inherent hemostatic and antimicrobial activity of saliva, together with the presence of growth factors, improves oral wound healing. Animal and human models appear to be very consistent in their respective molecular mechanisms of oral healing. Even at baseline, oral epithelial and fibroblast cells are genetically conditioned to respond to inflammation better than skin epithelial cells and fibroblasts. Oral keratinocytes are intrinsically more motile compared with skin keratinocytes, allowing for more rapid epithelial coverage. The intrinsic expressomic signatures of oral keratinocytes and fibroblasts differ markedly from their counterparts in the skin. Inflammatory pathways will be more active and sustained in skin wounds than in oral wounds. The important transcriptional regulators, PITX1, PITX2, and SOX2, have much greater (10×) expression in oral mucosa. Thus, the possibility exists to use the understanding of oral wound healing to improve skin wound healing. Saliva contains molecular constituents that actively promote wound healing, such as histatin-1, which has been shown to enhance skin cell migration. Overexpression of SOX2 and PITX1 has been shown to increase epithelial cell motility. Inducing SOX2 expression in the skin of a genetically engineered mouse improved skin wound healing. Future research will use “reprogramming” of cells within skin wounds to behave more like oral keratinocytes. This can be accomplished through the overexpression of genes that have yielded promising results in experimental systems. Dean White, DDS, retired Oral and Maxillofacial Surgeon, discussed surgeon burnout, including its etiology, demographics, risk factors, and effects on the quality of patient care. He also outlined strategies of prevention. Medical burnout has been defined as psychological exhaustion and can progress from emotional exhaustion to depersonalization and, eventually, a desire to leave medicine. The late stages of burnout coexist with major depression. The 4 major contributors to surgeon burnout include loss of control of one's work environment, loss of meaning in work, lack of mentorship, and a lack of administrative support. Physician burnout rates have varied from 53 to 72% within the reported data. Residents in surgery and emergency medicine are at the greatest risk of burnout. Women are 17% more likely to report the symptoms of burnout than are men. The risk factors for burnout include certain personality traits, including overachievement, type A personality, perfectionism, and obsessive compulsive behavior. Isolation in daily practice and the absorption of patient anxiety and demands are also risk factors for burnout. Burnout and depersonalization among oral and maxillofacial surgery residents have been identified and are thought to be associated with repeated shaming by attendings and senior residents. Physicians react to burnout by withdrawing from practice, engaging in self-destructive habits such as self-prescribing, considering suicide as a result of depression, and becoming less engaged with patients, leading to poor quality of care. The male physician suicide rate has been reported to be 1.4 to 2.3 times greater than that of the general population and the female physician suicide rate has been reported to be 2.5 to 4 times greater than that of the general population. The American College of Surgeons surveyed 7900 surgeons, with 700 surgeons reporting that a major medical error had occurred in the previous 3 months. These errors had a statistically significant correlation with all 3 domains of burnout: emotional exhaustion, depersonalization, and symptoms of depression. The solutions for surgeon burnout should include organizational and individual strategies. Organizations should foster a trustworthy and supportive environment for all physicians and staff, provide structured mentorship relationships, decrease the incidence of shaming, promote empathy, and develop policies that enhance physician well-being. Examples of physician well-being include creating a physician health committee that provides a nonthreatening, confidential avenue for physicians to obtain routine mental healthcare and proactive psychological support. The physician's health committee should also provide education and preventions of burnout and offer early intervention, treatment recommendations, relapse prevention, and help with re-entry into the medical staff after recovery. Finally, organizations should make available adequate support staff for physicians to decrease “busy” work and allow for family leave and flexibility to meet nonwork-related interests and obligations. Individuals could make efforts to mitigate burnout by creating more balance between work and family, performing regular physical and spiritual exercise, spending more time with family and friends, monitoring their inner emotional barometer, and looking for and acknowledging the signs of burnout. Louito C. Edje, MD, Residency Program Director, Department of Family Medicine, St Luke's Hospital, Maumee, OH, discussed the subject of building and sustaining a career. The importance and concept of “branding” was highlighted. A brand should be recognizable, consistent, and memorable. It is always present and binary, with either positive or negative attributes with respect to the individual or entity. A brand with only positive attributes is more advantageous, typically includes strength, and portrays the values and goals of the individual or entity. An appropriate Internet and social media presence, excellent curriculum vitae, and professional headshot are important components of a well-crafted brand. An Internet presence of a professional will exist whether self-defined or defined by third parties. An effort should be made to monitor and use the Internet, including the use of social media to build and maintain the brand to the intended vision. An excellent curriculum vitae should tell a compelling story and show the vision and worth of the individual and not just a list of places, memberships, and dates of services. A comprehensive curriculum vitae that is technologically enhanced could include links or hyperlinks to blogs, websites, webinars, short clips, or any other enduring materials from presentations. In addition, a focused curriculum vitae and a brief biography should be prepared. The focused curriculum vitae is also useful for audience-specific situations, should be less than 3 pages, and should include only the area of expertise and positions relevant to the audience. A brief biography could also be used at presentations and professional conferences as a narrative introduction. It should be 100 words or less, written in the third person, and should include pertinent history and honors. Finally, a professional headshot with full face and hair visible should be available as a part of the brand. The brand d