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.

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.

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.

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.

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.

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.

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.

Scarless wound healing: finding the right cells and signals.

From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/ß-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).

Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa.

Importance: Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating, often fatal, inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. Support and palliation are the only current therapies. Objective: To evaluate the safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with RDEB. Design, Setting, and Participants: Single-center phase 1 clinical trial conducted in the United States of 4 patients with severe RDEB with a measured area of wounds suitable for grafting of at least 100 cm2. Patients with undetectable type VII collagen keratinocyte expression were excluded. Interventions: Autologous keratinocytes isolated from biopsy samples collected from 4 patients with RDEB were transduced with good manufacturing practice-grade retrovirus carrying full-length human COL7A1 and assembled into epidermal sheet grafts. Type VII collagen gene-corrected grafts (approximately 35 cm2) were transplanted onto 6 wounds in each of the patients (n = 24 grafts). Main Outcomes and Measures: The primary safety outcomes were recombination competent retrovirus, cancer, and autoimmune reaction. Molecular correction was assessed as type VII collagen expression measured by immunofluorescence and immunoelectron microscopy. Wound healing was assessed using serial photographs taken at 3, 6, and 12 months after grafting. Results: The 4 patients (mean age, 23 years [range, 18-32 years]) were all male with an estimated body surface area affected with RDEB of 4% to 30%. All 24 grafts were well tolerated without serious adverse events. Type VII collagen expression at the dermal-epidermal junction was demonstrated on the graft sites by immunofluorescence microscopy in 9 of 10 biopsy samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (42%) at 12 months, including correct type VII collagen localization to anchoring fibrils. Wounds with recombinant type VII collagen graft sites displayed 75% or greater healing at 3 months (21 intact graft sites of 24 wound sites; 87%), 6 months (16/24; 67%), and 12 months (12/24; 50%) compared with baseline wound sites. Conclusions and Relevance: In this preliminary study of 4 patients with RDEB, there was wound healing in some type VII collagen gene-corrected grafts, but the response was variable among patients and among grafted sites and generally declined over 1 year. Long-term follow-up is necessary for these patients, and controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts. Trial Registration: clinicaltrials.gov Identifier: NCT01263379.

Emerging drugs for the treatment of wound healing.

INTRODUCTION: Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. AREAS COVERED: A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. EXPERT OPINION: The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

Chondromyxoid fibroma of the mandible in an adolescent: case report and microsurgical reconstructive option.

Chondromyxoid fibroma is a rare bony tumor that usually presents in the lower extremities of middle-aged adults. Involvement of the craniofacial skeleton is extremely rare. We present the unique case of an adolescent boy with a chondromyxoid fibroma of the mandible. The chondromyxoid fibroma in this patient recurred after initial treatment with curettage. We treated the recurrence with resection of the involved mandible and immediate reconstruction using a vascularized musculo-osseus seventh rib flap ("Eve procedure"). Despite complex reconstruction in adolescents due to skeletal immaturity, the rib flap has successfully grown with the patient up to 3 years postoperatively. Therefore, we believe the musculo-osseus rib flap is a feasible solution for complex ramus and condyle reconstruction of the growing mandible in the adolescent patient.

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.

Using bioabsorbable fixation systems in the treatment of pediatric skull deformities leads to good outcomes and low morbidity.

BACKGROUND: Bioabsorbable fixation systems have been widely employed in pediatric patients for cranial reconstruction, obviating the complications of hardware migration and imaging artifact occurring with metallic implants. Recent concern over complications unique to bioabsorbable materials, such as inflammatory reaction and incomplete resorption, necessitates additional conclusive studies to further validate their use in pediatric neurosurgery and craniofacial surgery. Likewise, long-term follow-up in this clinical cohort has not previously been described. METHODS: We included consecutive pediatric patients under the age of 2, from Lucile Packard Children's Hospital, who underwent cranial vault reconstruction with the use of a bioabsorbable fixation system between 2003 and 2010. Hospital records were queried for patient characteristics, intraoperative data, and postoperative complications. RESULTS: Ninety-five patients with the following preoperative pathologies were analyzed: craniosynostosis (87), cloverleaf skull (5), frontonasal dysplasia (1), and frontonasal encephalocele (2). Median age was 6 months (range 1-24 months). Average case duration was 204 minutes (range 40-392 min), with median of 154 mL blood loss (range 30-500 mL). Ninety-three percent of patients had 1-4 plates implanted with 48% receiving three plates. The median number of screws used was 59 (range 0-130). The median length of hospital stay was 4 days (range 2-127 days) with an average follow-up of 22 months (five postoperative visits). The complications related to hardware implantation included swelling (1%) and broken hardware (1%), the latter of which required reoperation. DISCUSSION: The bioabsorbable fixation systems for cranial vault reconstruction in children less than 2 years of age is safe with tolerable morbidity rates.

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.

Scarless fetal skin wound healing update.

Scar formation, a physiologic process in adult wound healing, can have devastating effects for patients; a multitude of pathologic outcomes, affecting all organ systems, stems from an amplification of this process. In contrast to adult wound repair, the early-gestation fetal skin wound heals without scar formation, a phenomenon that appears to be intrinsic to fetal skin. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to this scarless repair. Despite the great increase in knowledge gained over the past decades, the precise mechanisms regulating scarless fetal healing remain unknown. Herein, we describe the current proposed mechanisms underlying fetal scarless wound healing in an effort to recapitulate the fetal phenotype in the postnatal environment.

Fetal mouse skin heals scarlessly in a chick chorioallantoic membrane model system.

In mammals, the early-gestation fetus has the regenerative ability to heal skin wounds without scar formation. This observation was first reported more than 3 decades ago, and has been confirmed in a number of in vivo animal models. Although an intensive research effort has focused on unraveling the mechanisms underlying scarless fetal wound repair, no suitable model of in vitro fetal skin healing has been developed. In this article, we report a novel model for the study of fetal wound healing. Fetal skin from gestational day 16.5 Balb/c mice (total gestation, 20 days) was grafted onto the chorioallantoic membrane of 12-day-old chicken embryos and cultured for up to 7 days. At 48 hours postengraftment, circular wounds (diameter = 1 mm) were made in the fetal skin using a rotating titanium sapphire laser (N = 45). The tissue was examined daily by visual inspection to look for signs of infection and ischemia. The grafts and the surrounding host tissue were examined histologically. In all fetal skin grafts, the wounds completely reepithelialized by postinjury day 7, with regeneration of the dermis. Fetal mouse skin xenografts transplanted onto the chorioallantoic membrane of fertilized chicken eggs provides a useful model for the study of fetal wound healing. This model can be used as an adjunct to traditional in vivo mammalian models of fetal repair.

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.

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.

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.