Human platelet lysate enhances proliferation but not chondrogenic differentiation of pediatric mesenchymal progenitors.

BACKGROUND AIMS: Cell therapies have the potential to improve reconstructive procedures for congenital craniofacial cartilage anomalies such as microtia. Adipose-derived stem cells (ADSCs) and auricular cartilage stem/progenitor cells (CSPCs) are promising candidates for cartilage reconstruction, but their successful use in the clinic will require the development of xeno-free expansion and differentiation protocols that can maximize their capacity for chondrogenesis. METHODS: We assessed the behavior of human ADSCs and CSPCs grown either in qualified fetal bovine serum (FBS) or human platelet lysate (hPL), a xeno-free alternative, in conventional monolayer and 3-dimensional spheroid cultures. RESULTS: We show that CSPCs and ADSCs display greater proliferation rate in hPL than FBS and express typical mesenchymal stromal cell surface antigens in both media. When expanded in hPL, both cell types, particularly CSPCs, maintain a spindle-like morphology and lower surface area over more passages than in FBS. Both media supplements support chondrogenic differentiation of CSPCs and ADSCs grown either as monolayers or spheroids. However, chondrogenesis appears less ordered in hPL than FBS, with reduced co-localization of aggrecan and collagen type II in spheroids. CONCLUSIONS: hPL may be beneficial for the expansion of cells with chondrogenic potential and maintaining stemness, but not for their chondrogenic differentiation for tissue engineering or disease modeling.

Management of the Congenital Cleft Earlobe with a Conchal Cartilage Graft.

Congenital earlobe clefts are the most common lower auricular malformations. They represent a unique reconstructive challenge. The goal of surgery includes restoration of a natural lobular contour and volume as well as a fine surgical scar. Several surgical techniques have been described, most of which only address the cleft deformity but not the soft tissue deficiency. We hereby describe a technique which addresses both the cleft and improves soft tissue deficiency through a conchal cartilage graft.

Lop Ear to Conchal Microtia: An Algorithmic Surgical Approach.

BACKGROUND: The lop ear deformity is defined by a deficient helix and scapha, underdeveloped anthelix, and downfolding of the helix. The terminology used is still confusing, and the treatment is not entirely structured. The aim of this study was to provide a new systematic surgical approach of this deformity based on our center's experience. MATERIALS AND METHODS: All patients undergoing surgical correction of lop ears between 2007 and 2019 at Great Ormond Street Hospital were included. Patients' data, surgical techniques, and postoperative complications were recorded. RESULTS: Based on our records, we identified 3 surgical techniques for the correction of lop ears, based on the degree of deformity encountered. In a mild lop ear, correction was achieved with a modified otoplasty technique by improving the definition of the antihelix and superior crus. In a moderate deformity, additional remodeling of the lidded helix was performed (extended otoplasty), whereas for the severe lop ear, the amount of cupping and the deficient cartilage required formal reconstruction using a carved rib cartilage framework. There were a total of 109 patients and 146 lop ears: 58 mild, 27 moderate, and 61 severe lop ears. CONCLUSION: We feel that there is a point in the spectrum of congenital ear deformity when a severe lop ear becomes a conchal microtia and recommend this approach to simplify the management of these cases. This is intended to bring greater clarity to how to deal with lop ears, based on the severity of the deformity and the surgical techniques used.

Concepts Important to Patients With Facial Differences: A Qualitative Study Informing a New Module of the FACE-Q for Children and Young Adults.

OBJECTIVE: The concepts important to children and young adults who undergo treatments for facial differences are not well-defined. Measurement of treatment outcomes from the patient's perspective is necessary to ensure goals of treatment are met. We aimed to identify concepts important to children and young adults with facial differences through a qualitative study. DESIGN: An interpretive description qualitative approach was followed. Semistructured interviews were conducted, transcribed verbatim, and coded using a line-by-line approach. Qualitative analysis led to the development of a conceptual framework of outcomes important to patients. SETTING: Interviews were conducted in Canada and the United Kingdom at home, by telephone, or in the hospital. PARTICIPANTS: Participants (N = 72) were recruited between May and June 2014 from craniofacial clinics at the Hospital for Sick Children (Toronto) and Great Ormond Street Hospital (London). Participants included anyone with a visible and/or functional facial difference aged 8 to 29 years and fluent in English, excluding patients with a cleft. The sample included 38 females and 34 males, with a mean age of 13.9 years, and included 28 facial conditions (11 facial paralysis, 18 ear anomalies, 26 skeletal conditions, and 17 soft tissue conditions). RESULTS: Analysis led to identification of important concepts within 4 overarching domains: facial appearance, facial function, adverse effects of treatment, and health-related quality of life (psychological, social, and school function). CONCLUSIONS: Our study provides an understanding of concepts important to children and young adults with facial differences.

The Impact of COVID-19 on Plastic Surgery Training in the United Kingdom, Canada and Australia-A Cross-Sectional Study.

Background Surgical trainees worldwide have been thrust into a period of uncertainty, with respect to the implications COVID-19 pandemic will have on their roles, training, and future career prospects. It is currently unclear how plastic surgery trainees are being affected by COVID-19. This study examined the experience of plastic surgery trainees in Canada, the UK, and Australia to determine trainee roles during the early COVID-19 emergency response and how training changed during this time. Methods A cross-sectional survey-based study was designed for plastic surgery trainees in the UK, Canada and Australia. In total, 110 trainees responded to the survey. Statistical tests were conducted to determine differences in responses, based on year of training and country of residence. Results In total, 9.7% (10/103) of respondents reported being deployed to cover another service. There was a significant difference between redeployment based on country ( p = 0.001). Within the UK group, 28.9% of respondents were redeployed. For trainees not deployed, 95.5% (85/89) reported that there has been a reduction in operative volume. Ninety-seven (94.1%) respondents reported that there were ongoing teaching activities offered by their program. The majority of trainees (66.4%) were concerned about their training. There was a significant difference between overall concern and country ( p < 0.05). Conclusion In these unprecedented times, training programs in plastic surgery should be aware of the major impact that COVID-19 has had on trainees and will have on their training. The majority of plastic surgery trainees have experienced a reduction in surgical exposure but have maintained some form of regular teaching.

Recommendations for the Development and Reform of Microtia and Atresia Services.

BACKGROUND: The initial step in setting up standardized microtia-atresia service is investigating the current status of the service and comparing this to internationally recognized guidelines or care standards. In many countries, documented information about microtia care is lacking. This study is an initiative to guide reform efforts of national microtia service in any country. The UK care standards for microtia-atresia can be a useful model to help set up a comprehensive microtia-atresia service. METHODS: The authors conducted a survey to investigate different aspects of microtia service in Egypt. The major plastic surgery centers (n = 22) were surveyed by a structured questionnaire. The results were compared with the UK care standards for microtia-atresia to identify the aspects that need improvement. Thorough analysis of the main problems in microtia-atresia service is presented. RESULTS: The authors found that microtia service is fragmented between the surveyed centers with 65% of the centers treating less than 10 microtia cases annually. Multiple surgeons are responsible for ear reconstruction in 90% of centers and only 25% of them practise a multidisciplinary team approach. None of the centers uses validated tools of aesthetic or psychological patient-reported outcome measures. RECOMMENDATIONS: These 5 recommendations are the keys to reforming microtia service in any country:(1) Establishing nationally designated centers to concentrate the required expertise.(2) Assigning fewer high-volume surgeons to optimize the surgical outcomes.(3) Providing treatment by experienced multidisciplinary teams.(4) Using validated tools of patient-reported outcome measures.(5) Collecting and keeping standardized records for regular audit and intercenter studies.

Splinting After Ear Reconstruction: A Stepwise and Inexpensive Workflow Protocol.

BACKGROUND: Long-term postoperative splinting plays a role in the prevention of contracture of the grafted skin after a second-stage ear reconstruction. The scar retraction could lead to an unfavorable aesthetic outcome. Splinting could play a role to overcome or prevent the loss of projection and the obliteration of the sulcus. MATERIAL AND METHODS: We have defined the characteristics of an ideal long-term splint and present a stepwise clinical protocol for the fabrication of an ethylene-vinyl acetate splint. The splint was applied to all patients included in a prospective study on the postoperative splinting regime. Ethylene-vinyl acetate has proved its safety and longevity in dental prosthetics. CONCLUSIONS: Patient compliance was optimal, and no allergic reactions, pressure sores, or skin necrosis were reported. The splint is self-retaining and light weight. Because of its transparent color, it can be easily camouflaged. A stepwise clinical protocol for the fabrication of a low-cost patient-specific ear splint is presented.

Ear Aesthetics: Investigation by the Use of an Online Viral Survey.

INTRODUCTION: The ear is a key facial feature and yet few studies have previously assessed ear aesthetics. This study aimed to assess the anatomical components of the ear that have the greatest impact on the perception of ear aesthetics. MATERIALS AND METHODS: Three photographs of a male adult ear (close-up, lateral, posterior) were digitally manipulated such that in each, 1 anatomical element of the ear was either enlarged or reduced. A complete set of 16 photographs including a repeat of the original ear as a control were randomized and entered into an online survey that required respondents to rate the attractiveness of each ear on a scale of 1 (least attractive) to 10 (most attractive). The survey was disseminated using email and social media. RESULTS: A total of 248 responses were received, 155 women and 92 men. Respondents were grouped by demographics of age and occupation. Reducing (R) or enlarging (E) the helix (R, P = 0.0256; E, P = 0.003), concha (R, P = 0.0002; E, P = <0.0001) and lobule (R, P = 0.0006; E, P < 0.0001) had a significant effect on ratings of attractiveness. Altering the tragus had no significant effect (R, P = 0.448; E, P = 0.201). In lateral view, raising the height of the ear had a significant effect (P = <0.0001) but not in lowering the height (P = 0.3038). Increasing and decreasing the projection of the ears both had a significant effect (P < 0.0001). CONCLUSIONS: The results of this study have provided useful evidence regarding the anatomical components of the ear that have the greatest effect on ear aesthetics. Furthermore, this study has proven the usefulness of conducting research using viral online surveys.

An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing.

The global burden of disease associated with wounds is an increasingly significant public health concern. Current treatments are often expensive, time-consuming and limited in their efficacy in chronic wounds. The challenge of overcoming current barriers associated with wound care requires innovative management techniques. Regenerative medicine is an emerging field of research that focuses on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. This article provides an overview of the pathophysiology of wound healing and reviews the latest evidence on the application of the principal components of regenerative medicine (growth factors, stem cell transplantation, biomaterials and tissue engineering) as therapeutic targets. Improved knowledge and understanding of the pathophysiology of wound healing has pointed to new therapeutic targets. Regenerative medicine has the potential to underpin the design of specific target therapies in acute and chronic wound healing. This personalised approach could eventually reduce the burden of disease associated with wound healing. Further evidence is required in the form of large animal studies and clinical trials to assess long-term efficacy and safety of these new treatments.

The use of de-epithelialized skin flap in the surgical repair of terminal myelocystoceles.

BACKGROUND: Terminal myelocystocele is a severe form of spinal dysraphism characterized by cystic expansion of the terminal spinal cord that herniates through a deficiency of the posterior sacral spinal elements to fuse with the subcutaneous fat. Postnatal enlargement of the subcutaneous fluid-filled sac may result in progressive neurological deficit and threaten the viability of the overlying skin. Surgical repair entails spinal cord untethering, resection of nonfunctional neural elements and watertight reconstruction of the terminal thecal sac. Young age at the time of surgery, large dural defect, attenuated tissues and locally altered CSF dynamics frequently mean that wound complications including CSF leakage and pseudomeningocele formation are common. TECHNIQUE: With consideration of these requirements, we describe our surgical technique in terminal myelocystocele repair, which combines a novel surgical incision and for the first time in a neurosurgical setting, the use of a de-epithelialized skin flap to augment the closure. We report successful operative outcomes in three infant patients with terminal myelocystocele.

Chondrogenic differentiation of adipose tissue-derived stem cells within nanocaged POSS-PCU scaffolds: a new tool for nanomedicine.

Scaffold cellularization for cartilage engineering can aid implant properties, their retention and minimize repeated intervention, particularly in paediatric reconstructive craniofacial surgery. We developed novel bionanoscaffolds using paediatric adipose tissue-derived stem cells (hADSCs), an accessible autologous cell source, and POSS-PCU. Little is known about cellular responses to this nanomaterial, though it was used in human. We assessed: 1) POSS-PCU cellularization and bioaffinity to hADSCs; 2) hADSC chondrogenic differentiation ability in POSS-PCU; 3) whether bionanoscaffolds became encased within a vascular network and/or vascularised. POSS-PCU supported ADSC survival and proliferation and their migration and differentiation into cartilage within the nanoscaffold. Furthermore, after CAM-grafting, bionanoscaffolds were rapidly surrounded by blood vessels without any apparent negative reaction and erythrocytes of host origin were detected inside the scaffold, suggesting invasion from some capillaries. Altogether, this study demonstrates that POSS-PCU displays excellent bioactivity and hADSC/POSS-PCU bionanoscaffolds offer much promise for autologous cell-based tissue engineering for clinical applications. FROM THE CLINICAL EDITOR: In this study, human adipose tissue derived stem cells were used in combination with POSS-PCU nanoscaffolds to generate cartilage tissue demonstrating excellent bioactivity for autologous cell-based tissue engineering for clinical applications.

Further Refinements in Otoplasty Surgery: a modified approach to prevent suture extrusion in cartilage-suturing otoplasty using a postauricular dermofascial flap.

BACKGROUND: Suture extrusion has been reported to be the most common complication following cartilage-sparing otoplasty. Several studies have described various designs of postauricular flaps to cover the cartilage sutures and reduce the incidence of suture extrusion. PATIENTS AND METHODS: One hundred consecutive patients with prominent ears were operated between January 2018 and February 2023 using a de-epithelialized postauricular dermofascial flap that is performed as an adjunct to our cartilage-sparing otoplasty technique which is essentially a combined modified Mustardé and Furnas technique. The flap is used to cover the cartilage holding sutures with an extra layer of vascularized tissue to avoid the scar being directly over these sutures. RESULTS: The median age of patients was 12 (IQR 9-15) years. One out of the 100 patients (1%) developed a postauricular skin infection requiring surgical removal of sutures. Primary suture extrusion did not occur, compared to our earlier study of cartilage-sparing technique without the postauricular flap in which 17 out of 200 patients had suture extrusion (p=0.001). No hematoma occurred that necessitated return to the theatre. Skin necrosis and wound dehiscence did not occur in any case. No patients developed cartilage deformities or relapse requiring surgical correction. CONCLUSIONS: Combining cartilage-sparing otoplasty using sutures and the described postauricular dermofascial flap is simple to perform and has significantly reduced the complication rate and improved the outcome compared to cartilage-sparing otoplasty alone. We recommend using this flap for both primary and revisional otoplasty.

Patient factors associated with novel EAR-Q appearance, psychosocial, and social scales: A cross-sectional study and regression analysis.

INTRODUCTION: The EAR-Q is a rigorously validated patient-reported outcome measure, which evaluates ear appearance and health-related quality of life (HRQL) in patients with congenital or acquired ear conditions. The aim of this study was to conduct an exploratory analysis to examine the factors associated with EAR-Q appearance and HRQL scale scores. METHODS: In this study, 862 participants, aged 8-29 years, with congenital or acquired ear conditions, completed the EAR-Q as part of an international field-test study. Patients responded to demographic and clinical questions as well as the EAR-Q. Univariable and multivariable linear regression analyses were used to determine factors that were significant predictors for the scores on the EAR-Q Appearance, Psychological, and Social scales. RESULTS: Most participants were men (57.4%), awaiting treatment (55.0%), and had a microtia diagnosis (70.4%), with a mean age of 13 (±4) years. Worse ear appearance scores (p < 0.02) were associated with male gender, microtia, no history of treatment, ear surgery within 6 months, unilateral involvement, and greater self-reported ear asymmetry. Decreased psychological scores (p < 0.01) were associated with increasing participant age, no treatment history, recent ear surgery, and dissatisfaction with ears matching or overall dissatisfaction. Lower social scores (p ≤ 0.04) were associated with no treatment history, those awaiting surgery, ear surgery within the last 6 months, bilateral involvement, and self-reported ears matching or overall appearance. CONCLUSION: This analysis identified patient factors that may influence ear appearance and HRQL scale scores. These findings provide evidence of patient factors that should be adjusted for when undertaking future observational research designs using the EAR-Q in this patient population.

Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition.

Among children with multiple congenital melanocytic nevi, 25% have no established genetic cause, of whom many develop a hyperproliferative and severely pruritic phenotype resistant to treatment. Gene fusions have been reported in individual cases of congenital melanocytic nevi. We studied 169 patients with congenital melanocytic nevi in this study, 38 of whom were double wild type for pathogenic NRAS/BRAF variants. Nineteen of these 38 patients had sufficient tissue to undergo RNA sequencing, which revealed mosaic BRAF fusions in 11 of 19 patients and mosaic RAF1 fusions in 1 of 19. Recurrently, fusions involved the loss of the 5´ regulatory domain of BRAF or RAF1 but preserved the kinase domain. We validated all cases and detected the fusions in two separate nevi in 5 of 12 patients, confirming clonality. The absence of the fusion in blood in 8 of 12 patients indicated mosaicism. Primary culture of BRAF-fusion nevus cells from 3 of 12 patients demonstrated highly increased MAPK activation, despite only mildly increased BRAF expression, suggesting additional mechanisms of kinase activation. Trametinib quenched MAPK hyperactivation in vitro, and treatment of two patients caused rapid improvement in bulk tissue, improving bodily movement and reducing inflammation and severe pruritus. These findings offer a genetic diagnosis to an additional group of patients and trametinib as a treatment option for the severe associated phenotypes.

Management of the infected preauricular sinus.

INTRODUCTION: The preauricular sinus is a common finding in children and may often be complicated by infection. Complete excision of the sinus is the only definitive cure. Failure to recognise the presence of a sinus, particularly when infection erupts away from the sinus, may lead to inadequate management and unnecessary surgery. AIM: We report our experience in managing infected preauricular sinuses and highlight important points in our surgical technique. METHODS: A retrospective review was performed of our electronic patient database for all paediatric patients who underwent surgical excision of preauricular sinuses by the senior author at Great Ormond Street Hospital for Children between January 2013 and October 2022. RESULTS: A total of 10 patients underwent surgical management of 11 preauricular sinuses with a median follow-up time of 40 months (range 1-136). Eight patients underwent excision of the preauricular sinus due to infection. All infected cases affected the preauricular cheek skin and had previously undergone at least one unsuccessful surgical drainage prior to a referral to our unit. All cases were successfully operated on at our unit with no reported complications or recurrence. CONCLUSION: A lack of awareness of the presence of a sinus and identification of a preauricular pit by the inexperienced clinician will result in inadequate treatment of this condition and potentially unnecessary surgical procedures. Our paper highlights the importance of correctly identifying the extent of the sinus and describes a safe and reliable technique to ensure complete removal of the preauricular sinus with satisfactorily low recurrence rates.

Management of helical adhesion malformation.

Congenital auricular anomalies are common, however very few articles in the English literature address helical adhesion malformation, whereby the helix is adhered to the scapha. We describe a surgical approach to correct helical adhesion malformation which, unlike previously described methods, is simpler and results in an inconspicuous scar on the back of the ear. We illustrate our technique with an 11-year-old girl with bilateral helical adhesion malformations. Satisfactory ear shape was achieved bilaterally without complication. Meticulous dissection over the helix and exposure beyond the adhesion is of paramount importance in successfully correcting this malformation. Through a posterior auricular incision, this wide exposure and visualisation of the helix can be attained, with the added benefit of a scar hidden on the back of the ear.

Short-Term Treatment with Rho-Associated Kinase Inhibitor Preserves Keratinocyte Stem Cell Characteristics In Vitro.

Primary keratinocytes including keratinocyte stem cells (KSCs) can be cultured as epidermal sheets in vitro and are attractive for cell and gene therapies for genetic skin disorders. However, the initial slow growth of freshly isolated keratinocytes hinders clinical applications. Rho-associated kinase inhibitor (ROCKi) has been used to overcome this obstacle, but its influence on the characteristics of KSC and its safety for clinical application remains unknown. In this study, primary keratinocytes were treated with ROCKi Y-27632 for six days (short-term). Significant increases in colony formation and cell proliferation during the six-day ROCKi treatment were observed and confirmed by related protein markers and single-cell transcriptomic analysis. In addition, short-term ROCKi-treated cells maintained their differentiation ability as examined by 3D-organotypic culture. However, these changes could be reversed and became indistinguishable between treated and untreated cells once ROCKi treatment was withdrawn. Further, the short-term ROCKi treatment did not reduce the number of KSCs. In addition, AKT and ERK pathways were rapidly activated upon ROCKi treatment. In conclusion, short-term ROCKi treatment can transiently and reversibly accelerate initial primary keratinocyte expansion while preserving the holoclone-forming cell population (KSCs), providing a safe avenue for clinical applications.

Intrathoracic prosthesis in children in preventing post pneumonectomy syndrome: Its role in congenital single lung and post pneumonectomy situations.

BACKGROUND: Postpneumopnectomy syndrome (PPS) is an extreme rotation and malposition of mediastinum causing dynamic and symptomatic central airway compression, arisingafter pneumonectomy or more uncommonly, in congenital single lung physiology. Affected patients present with severe respiratory compromise. Intrathoracic prosthesis placement is an evolving technique in children that mitigate the effects of thoracic dead space. RESEARCH QUESTION: Assessment of clinical recovery and functional benefit in children undergoing placement of intrathoracic prosthesis following pneumonectomy or in congenital single lung situations. STUDY DESIGN AND METHODS: Retrospective chart review of patients at Great Ormond Street Hospital from 2010 to 2020 was performed of all patients who underwent intrathoracic tissue expander placement. We summarize the outcomes of twenty four children, including those with both congenital and postpneumonectomy PPS etiology. RESULTS: 24 Children who underwent placement of intrathoracic prosthesis for PPS in the study period with median age of 3.5 months and weight of 5 kg. Single lung etiology was congenital in 15 children (6 agenesis, 9 hypoplasia), and postpneumonectomy in 9 children. In seven patients, there was associated long segment tracheal stenosis. Pre operative ECMO was required in 2 patients, and pre operative ventilation was required in 12 patients all of whom had congenital single lung. Intrathoracic prosthesis placement was concurrent with intracardiac repair in 5 patients. There were no operative deaths, but one early postoperative death related to septicaemia. Median follow up was 75 months with 10 patients on continued respiratory support and 3 on nocturnal support with good quality of life. Two children needed reoperations for replacement of prosthesis. CONCLUSION: The use of tissue expanders is within the armamentarium of most plastic surgeons' practice. We also therefore advocate for a collaborative team approach involving Plastic and Cardiothoracic Surgery for surgical treatment of these patients. This multidisciplinary strategy has improved management of this rare and debilitating condition of PPS, thereby offering significant improvements in general progress of these sick children having single lung physiology. Evidence is still lacking on functional outcomes in these children and further work is necessary to prove that this is indeed achievable.

Modification of the cartilaginous framework for autologous ear reconstruction: Construction of a stable complete ring framework with grander highs and lows.

BACKGROUND: Successful microtia reconstruction involves fabrication of a framework with well-defined ear subunits. Tragal definition and deep conchal bowl are key elements to produce a natural well-defined and contoured ear. We describe a modification in the cartilage framework with the purpose of increasing framework stability, tragal definition and conchal bowl depth. METHODS: The tragus is placed on two cartilaginous bars (L-shaped), which are fixed to the framework base block creating a complete ring. These increase tragal projection and conchal depth. The tragus is carved angled posteriorly to have a shadowing effect on the absent auditory canal. Aesthetic outcome was assessed, at least 6 months after the second stage, on a 5-point ordinal scale (1-5) using the scoring system published in the UK microtia care standards and agreed on by the International Society for Auricular Reconstruction (ISAR). RESULTS: A total of 406 auricular reconstructions were performed in 363 patients (206 right, 114 left, 43 bilateral). After excluding cases who did not have second stage and those without complete photographs, 290 cases were assessed. The described modification in the framework carving was performed in 255 ears out of these 290 ears. The mean aesthetic score before and after the modification was 2.4 and 3.09 respectively for the tragus (p < 0.001), 2.2 and 2.95 for the intertragal notch (p < 0.001) and 2.77 and 3.49 for the concha (p < 0.001). CONCLUSIONS: This technical refinement has resulted in increased permanence and definition of the tragus and deeper and more aesthetic concha.