Translational Aspects of 3D and 4D Printing and Bioprinting.

Three-dimensional (3D) printed medical devices include orthopedic and craniofacial implants, surgical tools, and external prosthetics that have been directly used in patients. While the advances of additive manufacturing techniques in the production of medical devices have been on the rise, clinical translation of living cellular constructs face significant limitations in terms of regulatory affairs, process technology, and materials development. In this perspective, the current status-quo of 3D and four-dimensional (4D) (bio)printing is summarized, current advancements are discussed and the challenges that need to be addressed for improved industrial translation and clinical applications of bioprinting are highlighted. It is focused on a multidisciplinary approach in discussing the key translational considerations, from the perspective of industry, regulatory bodies, funding strategies, and future directions.

Artificial Intelligence in Facial Plastic Surgery: A Review of Current Applications, Future Applications, and Ethical Considerations.

From virtual chat assistants to self-driving cars, artificial intelligence (AI) is often heralded as the technology that has and will continue to transform this generation. Among widely adopted applications in other industries, its potential use in medicine is being increasingly explored, where the vast amounts of data present in electronic health records and need for continuous improvements in patient care and workflow efficiency present many opportunities for AI implementation. Indeed, AI has already demonstrated capabilities for assisting in tasks such as documentation, image classification, and surgical outcome prediction. More specifically, this technology can be harnessed in facial plastic surgery, where the unique characteristics of the field lends itself well to specific applications. AI is not without its limitations, however, and the further adoption of AI in medicine and facial plastic surgery must necessarily be accompanied by discussion on the ethical implications and proper usage of AI in healthcare. In this article, we review current and potential uses of AI in facial plastic surgery, as well as its ethical ramifications.

Translational Research Techniques for the Facial Plastic Surgeon: An Overview.

The field of facial plastic and reconstructive surgery (FPRS) is an incredibly diverse, multispecialty field that seeks innovative and novel solutions for the management of physical defects on the head and neck. To aid in the advancement of medical and surgical treatments for these defects, there has been a recent emphasis on the importance of translational research. With recent technological advancements, there are now a myriad of research techniques that are widely accessible for physician and scientist use in translational research. Such techniques include integrated multiomics, advanced cell culture and microfluidic tissue models, established animal models, and emerging computer models generated using bioinformatics. This study discusses these various research techniques and how they have and can be used for research in the context of various important diseases within the field of FPRS.

The Detroit Keloid Scale: A Validated Tool for Rating Keloids.

Background: Comparing keloid treatment modalities and assessing response to treatments may be predicted by a better classification system. Objectives: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI). Results: The inter-rater reliability was "substantial" for observer DKS and only "moderate" for VSS and observer POSAS (intraclass correlation coefficient were 0.80, 0.60, and 0.47, respectively). Pearson's correlation indicated "moderate" association between observer DKS with observer POSAS (ρ = 0.56, p < 0.001) and "substantial" relationship between observer DKS and VSS (ρ = 0.63, p < 0.001). Pearson's correlation indicated "moderate" association between patient portion of DKS and patient portion of POSAS and patient portion of the DKS and DLQI (0.61 and 0.60, respectively, p < 0.05). DKS total score consistently showed significant "substantial" relationship with POSAS total score (ρ = 0.65, p < 0.001). Conclusions: The DKS offers a validated keloid-specific outcome measure for comparing keloid treatments.

Midface Including Le Fort Level Injuries.

Le Fort fractures occur at uniform weak areas in the midface often due to blunt impact to the face. Sporting injuries are a common cause of facial trauma; however, use of protective equipment has reduced the number of sports-related injuries. All patients with traumatic injuries should be evaluated using Advanced Trauma Life Support protocol. Le Fort fractures can contribute to airway obstruction, and urgent intubation may be indicated. Surgery is indicated for most displaced Le Fort fractures to restore function and facial harmony. To facilitate reduction, the original occlusive relationship should be restored by placing the patient in MMF.

Postoperative pain with or without nasal splints after septoplasty and inferior turbinate reduction.

PURPOSE: To determine the effect of intranasal Doyle splints on postoperative pain following septoplasty and inferior turbinate reduction (ITR). Changes in Nasal Obstruction Symptom Evaluation (NOSE) scores were also evaluated. MATERIALS AND METHODS: A prospective cohort study conducted from January 2017 to January 2019. Patients were recruited if they experienced nasal obstruction due to septal deviation and inferior turbinate hypertrophy, and failed a one-month trial of intranasal corticosteroids. All patients underwent septoplasty with ITR, and either had Doyle splints or no splints placed. Patients were prescribed hydrocodone-acetaminophen 5-325 mg and asked to keep a daily log of pain medication use and visual analog scale (VAS) scores. Pain logs and NOSE scores were compared between patients who had splints versus patients who had no splints placed after septoplasty and ITR over the first postoperative week. NOSE scores were also collected at every postoperative visit (1 week, 1 month, and 6 months). RESULTS: Fifty-seven patients were enrolled (37 splints, 20 no-splints). The median postoperative pain VAS score was 3.0 (interquartile range [IQR] 2.0-5.0) for the splint group and 4.0 (IQR 2.0-5.0) for the no-splint group (P = 0.906). The median postoperative pain medication requirement in morphine equivalents at the first postoperative visit was 5.4 mg/day (IQR 2.0-13.3) for the splint group and 8.4 mg/day (IQR 1.8-15.3) for the no-splint group (P = 0.833). CONCLUSIONS: There were no statistically significant differences in postoperative pain VAS scores or pain medication use between the two groups. All patients experienced significant reductions in NOSE scores postoperatively.

Changes in Nasal Staphylococcus Colonization and Infection Rates After Nasal Surgery.

Background: The relationship between nasal flora and infection rates in patients undergoing nasal surgery is of interest. This relationship has been studied though changes that may take place due to surgery have never been elucidated. Objective: To assess colonization rates and changes in colonization patterns of methicillin-resistant or methicillin-sensitive Staphylococcus aureus (MRSA/MSSA) in nasal flora in patients undergoing nasal surgery and to determine whether colonization is a risk factor for postoperative infection. Methods: Patients undergoing nasal surgery including septoplasty, rhinoplasty, or nasal valve repair were recruited prospectively. Patients completed a survey preoperatively concerning risk factors of postoperative infection. Nasal swabs and cultures were done preoperatively and at 1 week postoperatively. Patients were assessed for surgical site infections postoperatively. Results: Fifty-five patients completed both preoperative and postoperative nasal swabs. Preoperative to postoperative colonization rates increased for MRSA (2-5%) and MSSA (22-36%). Of the 55 patients, 11 had a change in nasal flora postoperatively, 9 of whom were colonized with a Staphylococcus aureus strain. However, MSSA/MRSA colonization either preoperatively or postoperatively was not associated with surgical site infections. Gender was the only variable found to be associated with postoperative infection (p = 0.007) with all four infections occurring in females. Conclusions: MSSA and MRSA do not appear to be major risk factors for surgical site infection in nasal surgery, whereas prior nasal surgery is a risk factor. This is the first report of a change in nasal colonization after nasal surgery. This could have implications for antibiotic prophylaxis in select nasal surgery cases.

The Efficacy of Surgical Excision Plus Adjuvant Multimodal Therapies in the Treatment of Keloids: A Systematic Review and Meta-Analysis.

BACKGROUND: Research evaluating the efficacy of multimodal therapy for the treatment of keloids has reported combination regimens are most effective. OBJECTIVE: To compare recurrence rates for keloids treated with surgery plus one adjuvant intervention (dual therapy) versus surgery plus 2 or more adjuvant interventions (triple therapy). MATERIALS AND METHODS: Systematic literature review and meta-analysis of combination treatment for keloids. RESULTS: After full-text review, we included 60 articles representing 5,547 keloids: 5,243 received dual therapy, 259 received triple therapy, and 45 received quadruple therapy (the latter 2 groups were combined for analysis). The difference in recurrence rates between dual (19%) and triple therapy (11.2%) was not significant (p = .343). However, the difference in recurrence rates between dual therapy using surgery and radiation (18.7%) and triple therapy using surgery, radiation, and a third intervention (7.7%) was significant (p = .002). The differences for surgery and intralesional triamcinolone (TAC) showed trends toward significance, because keloids treated with dual therapy (21.7%) had a higher recurrence rate than those treated with triple therapy comprised of surgery, TAC, and another intervention (13.7%; p = .099). CONCLUSION: Triple therapy using surgery plus radiation and/or TAC as one of the adjuvant treatment modalities may achieve the lowest recurrence rates for keloids.

Facial Plastic Surgery Controversies: Keloids.

There are more than 11 million people in the world affected with keloids. Nevertheless, there is a lack of agreement in keloid management. Moreover, keloid research has left gaps in the understanding of its pathogenesis. Six questions are answered by 3 clinical scientists in an attempt to address common keloid controversies.

The Effects of Postoperative Intralesional Corticosteroids in the Prevention of Recurrent Earlobe Keloids: A Multispecialty Retrospective Review.

BACKGROUND: Effective treatment of keloids is challenging because the recurrence rate after surgical excision is high. Data on the best treatment practices are lacking. OBJECTIVE: To investigate the recurrence rate after surgical excision of earlobe keloids based on a postoperative intralesional corticosteroid injection protocol. MATERIALS AND METHODS: Retrospective chart review was performed from January 1, 2005, to March 31, 2016, of patients who had excision of ear keloids within the departments of dermatology, otorhinolaryngology, and plastic surgery. The number of postoperative injections was recorded, recurrence was reported by the patient, and the efficacy of an injection protocol was evaluated. RESULTS: There were 277 charts reviewed. Appropriate data were available for 184 patients. A statistically significant difference was found with recurrence associated with a lower number of injections (p < .001). Keloids were more likely to recur if they were not treated with a planned serial injection protocol (p < .001) or if they were treated outside the department of dermatology (p < .001). CONCLUSION: Intralesional corticosteroid injection after surgical excision of earlobe keloids statistically minimizes the risk of recurrence.

Robotic Buccal Mucosal Graft Ureteroplasty for Complex Ureteral Stricture.

OBJECTIVE: To demonstrate robot-assisted ureterolysis and buccal mucosal graft (BMG) ureteroplasty for the management of a complex, long recurrent ureteral stricture developing after ureterolysis, and also to demonstrate the use of near-infrared fluorescence (NIRF) imaging and intraoperative ureteroscopy during this procedure. METHODS: A 58-year-old man with a history of cabergoline treatment and a cardiac catheterization through the left groin presented with left flank pain and hydronephrosis. A computed tomography scan showed extensive fibrosis around the ureter and a ureteral stricture close to a tortuous left external iliac artery. A computed tomography-guided biopsy showed a benign fibrous tissue around the stricture with no increase in IgG4-expressing plasma cells. A robot-assisted ureterolysis with an omental wrap was performed. One year after the ureterolysis, the patient developed a recurrent ureteral stricture. Retrograde ureterogram showed a long, 6-cm stricture in the upper ureter. For the robotic ureteroplasty, the patient was placed in modified lateral position with port placement similar to the left pyeloplasty. Intraoperative flexible ureteroscopy and NIRF were used to define the distal extent of the stricture. For this, the ureteroscope was advanced until the stricture, and transilluminance of light from the ureteroscope was seen from the robotic camera using Firefly. Ureteral stricture was incised along its length over the ureteroscope. Two BMGs were harvested and sown together to obtain a longer graft. The graft was minimally defatted and brought in the abdomen through one of the ports. The composite graft was then sutured with 4-0 PDS as an onlay graft with the mucosal side facing toward the lumen of the ureter. Ureteroscopy was used to confirm patency, followed by stent placement. NIRF was used to confirm the viability of the ureter and the surrounding tissue. The omental flap was then harvested using a vessel sealer, fixed to the psoas fascia beneath the ureter, and then wrapped over the reconstructed ureter. The omental flap was also tacked to the side of the BMG with a suture to promote blood supply. RESULTS: The procedure was uncomplicated with an operative time of 280 minutes, an estimated blood loss of 75 mL, and an uneventful hospital stay. MAG3 Renal scan after 3 and 6 months of surgery showed no recurrence or obstruction. CONCLUSION: Despite the limitation of being a single case with only a 6-month follow-up, our report shows that robot-assisted BMG is a safe option for the reconstruction of long upper ureteral strictures. This procedure may be a less morbid alternative to an autotransplant and ileal ureter in these patients. However, outcomes need to be studied in a larger series with a longer follow-up.

Biological significance of genome-wide DNA methylation profiles in keloids.

OBJECTIVES/HYPOTHESIS: To obtain biological insight into keloid pathogenesis and treatment using pathway analysis of genome-wide differentially methylated gene profiles between keloid and normal skin. STUDY DESIGN: Prospective cohort. METHODS: Genome-wide profiling was previously done, with institutional review board approval, on six fresh keloid and six fresh normal skin tissue samples, using the Infinium HumanMethylation450 BeadChip kit. Statistically significant differentially methylated cytosine-phosphodiester bond-guanines (CpGs, n = 197) between keloid and normal tissue mapped to 152 genes. These genes were uploaded into Ingenuity Pathway Analysis (IPA) software to identify biological functions or regulatory networks interacting. The pathways (or "network") with an enrichment probability value ≤ .01 were subjected to a heuristic filter of keywords associated with keloid pathogenesis. RESULTS: Of the 197 CpGs, 191 were found in the IPA database and mapped to 152 unique genes. The top 10 hypermethylated genes were ACTR3C, LRRC61, PAQR4, C1orf109, SLCO2B1, CMKLR1, AHDC1, FYCO1, CCDC34, and CACNB2. The top 10 hypomethylated genes were GALNT3, SCML4, PPP1R13L, ANKRD11, WIPF1, MX2, IFFO1, DENND1C, CFH, and GHDC. IPA identified nine pathways with enrichment probability values ≤ .01, of which five (histidine degradation V1, phospholipase C signaling, colorectal cancer metastasis signaling, P2Y purinergic receptor signaling, and Gαi signaling) were associated with keloid keywords and contained "keloid genes" (P < .05). CONCLUSIONS: Genes differentially methylated between keloid and normal skin reside in known bionetwork pathways involved in critical biological functioning and signaling events in the cell. This information could be used to refine screening processes for biological significance to better understand keloid pathogenesis and to develop molecular-targeted therapy. LEVEL OF EVIDENCE: NA Laryngoscope, 127:70-78, 2017.

Genome-Wide Scan for Methylation Profiles in Keloids.

Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation.

Starting a cleft team: a primer.

Facial plastic surgeons have a comprehensive understanding of the challenges that patients with cleft lip and palate encounter in form and function. Because there are areas in the United States where access to cleft care is limited, opportunities exist for facial plastic surgeons to develop cleft teams to provide greater availability of services to patients. A consensus statement has been developed by the Cleft and Craniofacial Subcommittee of the Specialty Surgery Committee of the American Academy of Facial Plastic and Reconstructive Surgery that outlines strategies for facial plastic surgeons who are prepared to assume leadership roles in domestic multidisciplinary cleft team initiatives.

Differential management of scaphocephaly.

OBJECTIVES/HYPOTHESIS: The objective of this study was to review the outcomes of scaphocephaly management. We hypothesized that differential treatment of scaphocephaly based on age at correction and degree of severity yields consistently satisfying results while reducing the operative morbidity. STUDY DESIGN: Retrospective patient record review. METHODS: Three cranial vault-remodeling procedures with varying levels of aggressiveness (limited-access, partial, and total cranial-vault remodeling) were performed on patients with scaphocephaly from 1995 to 2010. More-aggressive procedures were performed on older patients and patients having more-severe deformities. Patient records were reviewed for age, weight, blood loss, and length of hospital stay, and cephalic indices (CIs) were calculated from computed tomography scans and clinical photographs. RESULTS: Fifty-one patients underwent surgery for scaphocephaly during the study period. The average estimated blood volume fraction lost was 0.41. The average length of hospital stay was 4.49 days. Pre- and postoperative CIs were calculable for 36 patients. The average preoperative CI was 68.7. The average postoperative CI was 79.3, for an average operative change of 15%. The three procedures had statistically different values for average length of stay. A trend was suggested for estimated blood loss and volume fraction lost. There was no statistically significant difference in CI outcomes. CONCLUSIONS: This study supports the concept of a proportionate response in the management of scaphocephaly. Less-aggressive procedures do not yield less-desirable results when properly selected to match the clinical situation of the individual patient.

Skeletal surgery in sleep apnea.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is a common condition, increasing in incidence along with obesity in Americans. This review looks at skeletal surgery to treat sleep apnea and recent advancements. RECENT FINDINGS: Skeletal surgery for OSA has improved with recent advancements in surgical genioplasty now able to advance the genioglossus as well as inferior mandible muscles without changing aesthetics. Some investigators have called for maxillomandibular advancement to be considered as a first-line therapy over continuous positive airway pressure. SUMMARY: Maxillomandibular advancement appears safe and effective for consideration as a first-line therapy for select patients with OSA.