Travel Distance and Spanish-Speaking are Associated with Delays in the Treatment of Cleft Palate.

OBJECTIVE: Delayed repair of cleft palate is associated with worse speech outcomes. Social determinants of health may influence the timing of surgery; however, there are no population health investigations to evaluate factors such as travel distance, language barriers, and payer. This study sought to identify factors that may interfere with timely cleft palate repair. DESIGN: Retrospective cohort. SETTING: National/multi-center. PATIENTS/PARTICIPANTS: All cleft palate repairs within California were extracted from 2000-2021. MAIN OUTCOMES MEASURES: The primary outcome was age at surgical repair, which was modeled with linear regression. Covariates included race, primary language, distance from patient home to hospital, socioeconomic status, primary payer, and managed care enrollment status. RESULTS: 11 260 patients underwent surgical repair of a cleft palate. Black race was associated with delayed repair (22 additional days, P = .004, 95% CI 67.00-37.7) along with Asian/Pacific-Islander race (11 additional days, P = .006, 95% CI 3.26-18.9) compared to white race. Spanish-speaking patients had significantly later cleft palate repairs by 19 days, (P < .001, 95% CI 10.8-27.7) compared with English-speaking. Further distances from the hospital were significantly associated with later cleft surgeries with out-of-state patients undergoing surgery 52 days later (P < .001, 95% CI 11.3-24.3). Managed care plans and Medi-Cal were significantly associated with earlier surgical repair compared with private insurance. CONCLUSION: Black, Asian Pacific Islander, and Spanish-speaking patients and greater distance traveled to hospital were associated with delayed cleft palate repairs. These results underscore the importance of addressing structural and social barriers to care to improve outcomes and reduce health disparities for patients with cleft palate.

Establishing a Xenograft Model with CD-1 Nude Mice to Study Human Skin Wound Repair.

BACKGROUND: A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice. METHODS: Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested. RESULTS: At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31 + immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26 + , and human nuclear antigen in the human scar without any staining of these human markers in the murine skin. CONCLUSION: The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model. CLINICAL RELEVANCE STATEMENT: Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.

Piezo inhibition prevents and rescues scarring by targeting the adipocyte to fibroblast transition.

While past studies have suggested that plasticity exists between dermal fibroblasts and adipocytes, it remains unknown whether fat actively contributes to fibrosis in scarring. We show that adipocytes convert to scar-forming fibroblasts in response to Piezo -mediated mechanosensing to drive wound fibrosis. We establish that mechanics alone are sufficient to drive adipocyte-to- fibroblast conversion. By leveraging clonal-lineage-tracing in combination with scRNA-seq, Visium, and CODEX, we define a "mechanically naïve" fibroblast-subpopulation that represents a transcriptionally intermediate state between adipocytes and scar-fibroblasts. Finally, we show that Piezo1 or Piezo2 -inhibition yields regenerative healing by preventing adipocytes' activation to fibroblasts, in both mouse-wounds and a novel human-xenograft-wound model. Importantly, Piezo1 -inhibition induced wound regeneration even in pre-existing established scars, a finding that suggests a role for adipocyte-to-fibroblast transition in wound remodeling, the least-understood phase of wound healing. Adipocyte-to-fibroblast transition may thus represent a therapeutic target for minimizing fibrosis via Piezo -inhibition in organs where fat contributes to fibrosis.

Enhanced recovery after cleft palate repair: A quality improvement project.

BACKGROUND: Children undergoing cleft palate repair present challenges to postoperative management due to several factors that can complicate recovery. Utilization of multimodal analgesic protocols can improve outcomes in this population. We report experience designing and implementing an enhanced recovery after surgery (ERAS) pathway for cleft palate repair to optimize postoperative recovery. AIMS: The primary aim was to implement an ERAS pathway with >70% bundle adherence to achieve a 30% reduction in postoperative opioid consumption within 12 months. Our secondary aims assessed intraoperative opioid consumption, length of stay, timeliness of oral intake, and respiratory recovery. METHODS: A multidisciplinary team of perioperative providers developed an ERAS pathway for cleft palate patients. Key drivers included patient and provider education, formal pathway creation and implementation, multimodal pain therapy, and target-based care. Interventions included maxillary nerve blockade and enhanced intra- and postoperative medication regimens. Outcomes were displayed as statistical process control charts. RESULTS: Pathway compliance was 77.0%. Patients during the intervention period (n = 39) experienced a 49% reduction in postoperative opioid consumption (p < .0001) relative to our historical cohort (n = 63), with a mean difference of -0.33 ± 0.11 mg/kg (95% CI -0.55 to -0.12 mg/kg). Intraoperative opioid consumption was reduced by 36% (p = .002), with a mean difference of -0.27 ± 0.09 mg/kg (95% CI -0.45 to -0.09 mg/kg). Additionally, patients in the intervention group had a 45% reduction in time to first oral intake (p = .02) relative to our historical cohort, with a mean difference of -3.81 ± 1.56 h (95% CI -6.9 to -0.70). There was no difference in PACU or hospital length of stay, but there was a significant reduction in variance of all secondary outcomes. CONCLUSION: Opioid reduction and improved timeliness of oral intake is possible with an ERAS protocol for cleft palate repair, but our protocol did not alter PACU or hospital length of stay.

Profibrotic Signaling Pathways and Surface Markers Are Up-Regulated in Fibroblasts of Human Striae Distensae and in a Mouse Model System.

BACKGROUND: Striae distensae are common disfiguring cutaneous lesions but lack effective treatments because of an incomplete understanding of their pathophysiology. Dermal fibroblasts likely play an important role. The authors investigate the cellular-molecular features distinguishing fibroblasts from human striae distensae and normal skin. The authors also develop a mouse model of striae distensae. METHODS: Human striae distensae and normal skin samples were compared for tensile strength and histologic structure. Fibroblasts from striae distensae and normal skin were isolated by fluorescence-activated cell sorting for gene expression analysis. Immunofluorescence staining and fluorescence-activated cell sorting were used to confirm gene expression data at the protein level. A mouse model of striae distensae formation was created by administering corticosteroids and mechanically loading the dorsal skin. RESULTS: Human striae distensae exhibited reduced tensile strength, more disordered collagen fibers, and epidermal atrophy compared to human normal skin. There were 296 up-regulated genes in striae distensae fibroblasts, including the profibrotic lineage and surface marker CD26. Up-regulated genes were involved in profibrotic and mechanoresponsive signaling pathways (TGFß and FAK-PI3-AKT-signaling). In contrast, 571 genes were down-regulated, including CD74 and genes of the AMPK pathway. Increased CD26 and decreased CD74 expression was confirmed by fluorescence-activated cell sorting and immunofluorescence. Similar cutaneous histologic and gene expression changes were induced in hypercortisolemic mice by mechanically loading the dorsal skin. CONCLUSIONS: Fibroblasts from human striae distensae exhibit increased profibrotic and decreased antifibrotic signaling. CD26 and CD74 are promising surface markers that may be targeted therapeutically. The authors' mouse model of striae distensae can be used as a platform to test the efficacy of potential therapeutic agents. CLINICAL RELEVANCE STATEMENT: Striae distensae are common disfiguring cutaneous lesions whose etiology remains elusive, which has hindered development of effective treatment strategies. Dermal fibroblasts likely play an important role. The authors sought to elucidate the key cellular-molecular pathways distinguishing fibroblasts in striae distensae from those in normal skin.

Out-of-Pocket Costs and Provider Payments in Cleft Lip and Palate Repair.

BACKGROUND: As healthcare spending within the United States grows, payers have attempted to curb spending through higher cost sharing for patients. For families attempting to balance financial obligations with their children's surgical needs, high cost sharing could place families in difficult situations, deciding between life-altering surgery and bankruptcy. We aim to investigate trends in patient cost sharing and provider payments for cleft lip and palate repair. METHODS: The IBM® MarketScan® Commercial Database was queried to extract patients younger than 18 years who underwent primary or secondary cleft lip and/or palate repair from 2007 to 2016. Financial variables included gross payments to the provider (facility and/or physician), net payment as reported by the carrier, coordination of benefits and other savings, and the beneficiary contribution, which consisted of patients' coinsurance, copay, and deductible payments. Linear regression was used to evaluate trends in payments over time. Poisson regression was used to trend the proportion of patients with a nonzero beneficiary contribution. All financial values were adjusted to 2016 dollars per the consumer price index to account for inflation. RESULTS: The sample included 6268 cleft lip and 9118 cleft palate repair episodes. Total provider payments increased significantly from 2007 to 2016 for patients undergoing cleft lip (median, $2527.33 vs $5116.30, P 0.008) and palate ($1766.13 vs $3511.70, P < 0.001) repair. Beneficiary contribution also increased significantly for both cleft lip ($155.75 vs $193.31, P < 0.001) and palate ($124.37 vs $183.22, P < 0.001) repair, driven by an increase in deductibles ( P < 0.002). The proportion of cleft palate patients with a nonzero beneficiary contribution increased yearly by 1.6% ( P = 0.002). Higher provider payments and beneficiary contributions were found in the Northeast ( P < 0.001) and South ( P < 0.011), respectively, for both cleft lip and palate repair. CONCLUSIONS: The US national data demonstrate that for commercially insured patients with cleft lip and/or palate, there has been a trend toward higher patient cost sharing, most pronounced in the South. This suggests that patients are bearing an increased cost burden while provider payments are simultaneously accelerating. Additional studies are needed to understand the impact of increased cost sharing on parents' decision to pursue cleft lip and/or palate repair for their children.

Understanding Scarring in the Oral Mucosa.

Significance: Skin inevitably heals with the formation of a fibrotic scar. Patients affected by skin scarring suffer from long-term psychological and physical burdens. Recent Advances: Since the discovery of fetal scarless skin-wound healing, research has hoped to identify and mimic scarless healing for adult skin. Oral mucosa healing in adults provides the closest example to fetal scarless healing. Injuries to the oral mucosa heal with very minimal scarring. Understanding the mechanisms through which this process occurs may bring us closer to achieving scarless healing in adults. Critical Issues: In this review, we summarize the current evidence that illustrates distinct mechanisms involved in oral mucosal healing. We discuss the role of the oral niche in contributing to wound repair. The intrinsic properties of immune cells, fibroblasts, and keratinocytes within the oral mucosa that support regenerative repair are provided. We highlight the contribution of cytokines, growth factors, and chemokine secretion in permitting a scarless mucosal environment. Furthermore, we discuss the role of stem cell-like progenitor populations in the mucosa that may contribute to wound healing. We also provide suggestions for future studies that are needed to achieve scarless healing in adults. Future Directions: Many characteristics of the oral mucosa have been shown to contribute to decreased scarring, but the specific mechanism(s) is unclear. Advancing our understanding of oral healing may yield therapeutic therapies that can be used to overcome dermal scarring.

A Systematic Review of Mandibular Distraction Osteogenesis Versus Orthodontic Airway Plate for Airway Obstruction Treatment in Pierre Robin Sequence.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. DESIGN: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. MAIN OUTCOME MEASURES: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). RESULTS: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. CONCLUSIONS: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison.

Rates of Revision and Obstructive Sleep Apnea after Surgery for Velopharyngeal Insufficiency: A Longitudinal Comparative Analysis of More Than 1000 Operations.

BACKGROUND: The purpose of this study was to evaluate the comparative incidence of obstructive sleep apnea following velopharyngeal insufficiency surgery in the United States. METHODS: A retrospective analysis of cleft and noncleft pediatric patients who underwent velopharyngeal insufficiency surgery was performed using the IBM MarketScan Commercial Database. Patients were tracked longitudinally from 2007 to 2016 to evaluate the incidence of obstructive sleep apnea. Multivariable regression was used to evaluate predictors of postoperative obstructive sleep apnea and surgical revision. RESULTS: A total of 1098 patients underwent a pharyngeal flap (61.0 percent), sphincter pharyngoplasty (22.2 percent), or palatal lengthening with or without island flaps (16.8 percent). Diagnoses were predominantly cleft lip and/or palate (52.8 percent) and congenital oropharyngeal anomalies (42.6 percent). Eighty patients (7.3 percent) developed obstructive sleep apnea at an average of 10.2 months postoperatively. Predictors of obstructive sleep apnea included older age (p = 0.014) and head and neck neoplasm (p = 0.011). The obstructive sleep apnea rate following sphincter pharyngoplasty was 11.1 percent, compared to 7.2 percent after pharyngeal flap surgery. Compared to sphincter pharyngoplasty, pharyngeal flap surgery was associated with a lower risk of further surgery (OR, 0.43; p = 0.010). Of patients with cleft lip and/or palate, 35 developed obstructive sleep apnea (6.0 percent) without a significant association with procedure type. CONCLUSIONS: In this national claims database analysis of cleft and noncleft pediatric patients, the rate of obstructive sleep apnea following velopharyngeal insufficiency surgery was not significantly different for pharyngeal flap compared to sphincter pharyngoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Striae Distensae: Scars without Wounds.

SUMMARY: Striae distensae, or stretch marks, are common linear lesions of atrophic skin characterized histologically by epidermal atrophy, absent rete ridges, and alterations in connective tissue architecture. Hormonal excess, mechanical stress, and genetic predisposition are all associated with striae distensae, but their exact pathogenesis remains unknown. Despite a multitude of options, no single treatment has yet proven effective. In this article, the authors describe an up-to-date overview of striae distensae in terms of their etiology, pathophysiology, and therapeutic options. Further research is required to better elucidate their pathophysiology and to develop targeted effective treatments.

Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring.

Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage-positive fibroblasts (EPFs) are known to function in scarring, but Engrailed-1 lineage-negative fibroblasts (ENFs) remain poorly characterized. Using cell transplantation and transgenic mouse models, we identified a dermal ENF subpopulation that gives rise to postnatally derived EPFs by activating Engrailed-1 expression during adult wound healing. By studying ENF responses to substrate mechanics, we found that mechanical tension drives Engrailed-1 activation via canonical mechanotransduction signaling. Finally, we showed that blocking mechanotransduction signaling with either verteporfin, an inhibitor of Yes-associated protein (YAP), or fibroblast-specific transgenic YAP knockout prevents Engrailed-1 activation and promotes wound regeneration by ENFs, with recovery of skin appendages, ultrastructure, and mechanical strength. This finding suggests that there are two possible outcomes to postnatal wound healing: a fibrotic response (EPF-mediated) and a regenerative response (ENF-mediated).

Wounds Inhibit Tumor Growth In Vivo.

OBJECTIVE: The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo. SUMMARY OF BACKGROUND DATA: Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo. METHODS: To determine the interaction of tumors and wounds, we developed a tumor xenograft/allograft (human head and neck squamous cell carcinoma SAS/mouse breast carcinoma 4T1) wound mouse model. We examined tumor growth with varying temporospatial placement of tumors and wounds or ischemic flap. In addition, we developed a tumor/wound parabiosis model to understand the ability of tumors and wounds to recruit circulating progenitor cells. RESULTS: Tumor growth inhibition by full thickness excisional wounds was dose-dependent, maintained by sequential wounding, and relative to distance. This effect was recapitulated by placement of an ischemic flap directly adjacent to a xenograft tumor. Using a parabiosis model, we demonstrated that a healing wound was able to recruit significantly more circulating progenitor cells than a growing tumor. Tumor inhibition by wound was unaffected by presence of an immune response in an immunocompetent model using a mammary carcinoma. Utilizing functional proteomics, we identified 100 proteins differentially expressed in tumors and wounds. CONCLUSION: Full thickness excisional wounds have the ability to inhibit tumor growth in vivo. Further research may provide an exact mechanism for this remarkable finding and new advances in wound healing and tumor biology.

Evidenced-Based Practice Among Trainees: A Survey on Facial Trauma Wound Management.

OBJECTIVE: Assess whether facial trauma wound care and antibiotic use recommendations are guided by evidence-based practice (EBP) or practice patterns, and investigate strategies to improve EBP adoption among surgical trainees. DESIGN: We conducted a survey of all trainees who manage facial trauma (general surgery, emergency medicine, plastic surgery, otolaryngology) to assess clinical knowledge and sources of treatment recommendations. Clinical questions were based on Oxford Center for Evidence-Based Medicine Level 1 or 2 evidence. We measured internal validity of questions using Cronbach's α. Results were weight-adjusted for nonresponse and then analyzed using Welch t test and descriptive statistics. STUDY SETTING: Stanford Hospital and Clinics, a Level I trauma center. RESULTS: Response rate was 50.3% overall (78/155). For recommendations on facial trauma wound and antibiotic use, nonspecialty junior residents most frequently relied on their own senior or specialty residents (79.1%); nonspecialty senior residents relied on specialty residents (67.9%). Specialty junior residents most often relied on their own senior residents (51.0%), the majority of whom made recommendations based on their own knowledge (73.2%). Questions assessing EBP knowledge had Cronbach's α of 0.98; response accuracy was similar between specialty and nonspecialty residents (54.6% vs 55.5%, p = 0.96). When provided recommendations that conflict with EBP, both nonspecialty and specialty residents more frequently followed recommendations rather than EBP; junior residents reported doing so to avoid conflict with superiors. Total 92.6% of surveyed residents felt cross-departmental EBP guidelines would improve patient care. CONCLUSIONS: Facial trauma wound care and antibiotic recommendations disseminate down seniority and from craniofacial specialty to nonspecialty residents, yet knowledge of EBP among senior specialty and nonspecialty residents was weak. EBP may be difficult to adopt in the absence of consensus society guidelines. To address this gap, we published a review of EBP for facial trauma and plan to update our trauma manual with cross-departmental guidelines to facilitate EBP adoption among trainees.

Applied Online Crowdsourcing in Plastic and Reconstructive Surgery: A Comparison of Aesthetic Outcomes in Unilateral Cleft Lip Repair Techniques.

BACKGROUND: Aesthetic outcomes of unilateral cleft lip repairs have important psychosocial implications for patients who are heavily influenced by social perceptions. Online crowdsourcing offers the unique potential to efficiently recruit large numbers of laypeople to assess public perception. The aim of this study was to use the online crowdsourcing platform Mechanical Turk to compare the postoperative outcomes of Fisher, Millard, and Mohler cleft lip repair techniques. METHODS: Two hundred fifty-four participants were recruited through Mechanical Turk to evaluate 29 cropped and deidentified photographs of children, 8 photographs were controls without cleft lips and 21 were children with unilateral cleft lips who had undergone Fisher, Millard, or Mohler repairs (7 in each group). Respondents were asked whether a scar was present, whether they would be personally satisfied with the surgical result and used a Likert scale from 1 to 5 to rate overall appearance, scar severity, and nasal symmetry. RESULTS: Fewer respondents reported that a scar was present when assessing postoperative photographs of Fisher repairs (70.3 ± 8.6%) compared with Millard (92.0 ± 1.5%) or Mohler (88.8 ± 3.1%) repairs. Average rating of scar severity was also lower for Fisher (1.9) compared with Millard (2.6) or Mohler (2.6) repairs. Average ratings of nose symmetry, general appearance, and satisfaction with operative result were not statistically significantly different between the repair groups. CONCLUSIONS: This study demonstrates the potential of online crowdsourcing to assess public perception of plastic surgery outcomes. The Mechanical Turk platform offers a reduction in selection bias, ease of study design, and enhanced efficiency of large-scale participant recruitment. Results indicate that the Fisher repair led to the most favored aesthetic outcomes compared with the Millard and Mohler techniques, particularly with regard to scar severity. Crowdsourcing is a powerful tool to assess layperson perception of plastic surgery outcomes and can be used to better guide surgical decision-making.

Treatment of Full-Thickness Skin Wounds with Blood-Derived CD34+ Precursor Cells Enhances Healing with Hair Follicle Regeneration.

Objective: Epidermal CD34+ stem cells located in the hair follicle (HF) bulge area are capable of inducing HF neogenesis and enhancing wound healing after transplantation. In this study, we observed CD34+ cells derived from blood directly participate in dermal regeneration during full-thickness excisional wound healing. Approach: We isolated and in vitro expanded a subset of hematopoietic stem cell (HSC)-like precursor cells from the peripheral blood of adult mice with the surface markers: CD34+, leucine rich repeat containing G protein-coupled receptor 5 (LGR5)+, CD44+, c-kit+, lineage negative (lin-), and E-cadherin-. These blood-derived precursor cells (BDPCs), can be further differentiated into epithelial-like cells (eBDPCs) and secret fibroblast growth factor 9 (Fgf9) protein. Result: When transplanted into full-thickness skin wounds, eBDPC treatment produced accelerated healing and enhanced skin structure regeneration with less dermal scar formation. Also, HF neogenesis (HFN) was observed with incorporation of labeled BDPCs in the wound area. Innovation:Nondermal-derived CD34+ cells (BDPCs) from the adult unmobilized peripheral blood are capable of in vitro expansion and differentiation.Successful establishment of an in vitro technical platform for BDPCs expansion and differentiation.The in vitro expanded and differentiated epithelial-like cells (eBDPCs) enhance wound healing and directly contribute to skin regeneration and HFN. Conclusion: BDPCs isolated and expanded from adult peripheral blood may provide a possible new cell-based treatment strategy for HF neogenesis and skin wound regeneration.

Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODSAutologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTSNo participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSIONC7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATIONClinicaltrials.gov identifier: NCT01263379.FUNDINGEpidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran's Affairs Medical Center, and the Dermatology Foundation.

Retrospective cohort-based comparison of intraoperative liposomal bupivacaine versus bupivacaine for donor site iliac crest analgesia during alveolar bone grafting.

INTRODUCTION: Bone grafting of alveolar clefts is routinely performed with cancellous bone harvested from the iliac crest. Graft site morbidity is frequently seen, with early postoperative pain being one of the most common complaints. Liposomal bupivacaine (LB) has been demonstrated to provide improvement in postoperative pain for patients undergoing bunionectomy or hemorrhoidectomy, which may translate to patients requiring iliac crest bone graft harvest. METHODS: Thirty-eight patients undergoing iliac crest bone harvest were included in the study. Twenty-one patients underwent open iliac crest bone graft harvest with administration of 0.25% bupivacaine at the hip donor site, while 17 patients received local infiltration of 1.3% liposomal bupivacaine. Patient-reported pain scores, total narcotic use, length of stay, and postoperative steps were monitored. RESULTS: There were no significant differences in age, weight, distribution of clefts, or choice of donor hip between the two groups. There were no significant differences in length of hospitalization stay. However, differences were noted in average postoperative pain scores at five of six time points in the first 24 h, total oral morphine equivalents administered (4.7 ±â€¯5.3 vs. 14.3 ±â€¯12.0), and steps at postoperative days one to three (p < 0.001, for all three days) for patients receiving 1.3% LB versus 0.25% bupivacaine, respectively. CONCLUSION: Reduced pain scores and increased postoperative activity highlight the potential of LB to improve postoperative pain management in children undergoing iliac crest bone harvest for alveolar bone grafting.

Assessing the Fisher, Mohler, and Millard Techniques of Cleft Lip Repair Surgery With Eye-Tracking Technology.

BACKGROUND: Cleft lip repair is essential to restoring physiologic function and ensuring social and psychological well-being in children with orofacial clefts. It is important to critically study various techniques to understand the elements of the lip and nasal repair that contribute to favorable results. Here, we use eye-tracking technology to evaluate how viewers analyze images of cleft lips repaired by the Fisher, Millard, or Mohler techniques. METHODS: Thirty viewers were shown 5 images without deformity and 5 images each of unilateral cleft lips repaired by the Fisher, Millard, or Mohler techniques. Viewers assessed the esthetic quality of images on a Likert scale while eye-tracking technology analyzed their gaze patterns. RESULTS: Of the 3 repair techniques, viewers found Fisher repairs most esthetically pleasing (mean ± standard error, 6.91 ± 0.13). Mohler repairs were next most attractive at (6.47 ± 0.13), followed by Millard repairs at (5.60 ± 0.14). The proportion of time spent in fixed gaze on the nose and upper lip was greatest for Millard repairs (58.3% ± 0.4%) and least for Fisher repairs (51.9% ± 0.5%). Viewers fixated most frequently on the nose and upper lip in Millard repairs (83.2% ± 0.5%) and least frequently in Fisher repairs (75.3% ± 0.5%). When examining the Millard compared with Fisher and Mohler repairs, viewers spent more time and fixations on the ipsilateral lip, nose, and repair scar than on the contralateral lip. CONCLUSIONS: The esthetics of the Fisher repair appear to be favored as measured by Likert scores and gaze data. Eye-tracking technology may be a useful tool to assess outcomes in plastic surgery.

Pediatric Facial Trauma.

Pediatric facial fracture management is often complex and demanding. The structure and topography of the pediatric craniofacial skeleton are profoundly different from the mature skull. Consequently, the pediatric facial skeleton responds differently to traumatic force. Although the incidence of pediatric facial trauma is higher than in the adult population, the incidence of facial fracture is significantly lower. The management in younger patients is often more conservative because of potential growth impairment. As the facial skeleton matures, more conventional surgical approaches become appropriate. This review provides an understanding of the unique elements of facial fracture management in the pediatric population.