Identification of the Human Skeletal Stem Cell.

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

Deferoxamine topical cream superior to patch in rescuing radiation-induced fibrosis of unwounded and wounded skin.

Topical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W-D100), DFO 1 mg patch (W-DP), control cream (W-Vehicle), and irradiated untreated wounds (W-IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8-isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.

Pharmacological and cell-based treatments to increase local skin flap viability in animal models.

Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10-15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

A Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue.

BACKGROUND: Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia. METHODS: The ActinCreER/R26VT2/GK3 Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions. RESULTS: Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105highSca1low, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105lowSca1high and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice. CONCLUSIONS: These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.

Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration.

During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis-which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.

Integrated spatial multiomics reveals fibroblast fate during tissue repair.

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.

A Review of Radiation-Induced Vascular Injury and Clinical Impact.

ABSTRACT: The number of cancer survivors continues to increase because of advances in therapeutic modalities. Along with surgery and chemotherapy, radiotherapy is a commonly used treatment modality in roughly half of all cancer patients. It is particularly helpful in the oncologic treatment of patients with breast, head and neck, and prostate malignancies. Unfortunately, among patients receiving radiation therapy, long-term sequalae are often unavoidable, and there is accumulating clinical evidence suggesting significant radiation-related damage to the vascular endothelium. Ionizing radiation has been known to cause obliterative fibrosis and increased wall thickness in irradiated blood vessels. Clinically, these vascular changes induced by ionizing radiation can pose unique surgical challenges when operating in radiated fields. Here, we review the relevant literature on radiation-induced vascular damage focusing on mechanisms and signaling pathways involved and highlight microsurgical anastomotic outcomes after radiotherapy. In addition, we briefly comment on potential therapeutic strategies, which may have the ability to mitigate radiation injury to the vascular endothelium.

Nipple-areola-complex preservation and obesity-Successful in stages.

BACKGROUND: The superiority of nipple-sparing mastectomy (NSM) on breast aesthetics and patient-reported outcomes has previously been demonstrated. Despite 42.4% of adults in the United States being considered obese, obesity has been considered a contraindication to NSM due to concerns for nipple areolar complex (NAC) malposition or ischemic complications. This report investigates the feasibility and safety of a staged surgical approach to NSM with immediate microsurgical breast reconstruction in the high-risk obese population. METHODS: Only patients with a body mass index (BMI) of >30 kg/m2 who underwent bilateral mastopexy or breast reduction for correction of ptosis or macromastia (stage 1), respectively, followed by bilateral prophylactic NSM with immediate microsurgical breast reconstruction with free abdominal flaps (stage 2) were included in the analysis. Patient demographics and surgical outcomes were analyzed. RESULTS: Fifteen patients with high-risk genetic mutations for breast cancer with a mean age and BMI of 41.3 years and 35.0 kg/m2 , respectively, underwent bilateral staged NSM with immediate microsurgical breast reconstruction (30 breast reconstructions). At a mean follow-up of 15.7 months, complications were encountered following stage 2 only and included mastectomy skin necrosis (5 breasts [16.7%]), NAC necrosis (2 breasts [6.7%]), and abdominal seroma (1 patient [6.7%]) all of which were considered minor and neither required surgical intervention nor admission. CONCLUSIONS: Implementation of a staged approach permits NAC preservation in obese patients who present for prophylactic mastectomy and immediate microsurgical reconstruction.

AI-based Cleft Lip and Palate Surgical Information is Preferred by Both Plastic Surgeons and Patients in a Blind Comparison.

INTRODUCTION: The application of artificial intelligence (AI) in healthcare has expanded in recent years, and these tools such as ChatGPT to generate patient-facing information have garnered particular interest. Online cleft lip and palate (CL/P) surgical information supplied by academic/professional (A/P) sources was therefore evaluated against ChatGPT regarding accuracy, comprehensiveness, and clarity. METHODS: 11 plastic and reconstructive surgeons and 29 non-medical individuals blindly compared responses written by ChatGPT or A/P sources to 30 frequently asked CL/P surgery questions. Surgeons indicated preference, determined accuracy, and scored comprehensiveness and clarity. Non-medical individuals indicated preference. Calculations of readability scores were determined using seven readability formulas. Statistical analysis of CL/P surgical online information was performed using paired t-tests. RESULTS: Surgeons, 60.88% of the time, blindly preferred material generated by ChatGPT over A/P sources. Additionally, surgeons consistently indicated that ChatGPT-generated material was more comprehensive and had greater clarity. No significant difference was found between ChatGPT and resources provided by professional organizations in terms of accuracy. Among individuals with no medical background, ChatGPT-generated materials were preferred 60.46% of the time. For materials from both ChatGPT and A/P sources, readability scores surpassed advised levels for patient proficiency across seven readability formulas. CONCLUSION: As the prominence of ChatGPT-based language tools rises in the healthcare space, potential applications of the tools should be assessed by experts against existing high-quality sources. Our results indicate that ChatGPT is capable of producing high-quality material in terms of accuracy, comprehensiveness, and clarity preferred by both plastic surgeons and individuals with no medical background.

Microsurgical Breast Reconstruction can be Performed Safely in Patients with Obesity.

BACKGROUND: Numerous studies have shown that obesity is a risk factor for postoperative complications following breast reconstruction. Hence, obesity has traditionally been considered a relative contraindication to microsurgical breast reconstruction. In this study, we investigated the impact of obesity on outcomes following microsurgical breast reconstruction. METHODS: A retrospective analysis of 200 consecutive patients who underwent microsurgical breast reconstruction with free abdominal flaps was performed. Subjects were divided into Nonobese (body mass index [BMI] < 30 kg/m2) and Obese (BMI ≥ 30 kg/m2) cohorts. Univariate and multivariate analyses were performed to evaluate differences in patient characteristics, complication rates, and efficiency metrics between the two groups. RESULTS: Of the 200 subjects included in the study, 128 were Nonobese, 72 were Obese. The prevalence of diabetes (3.9 vs. 16.9%, p = 0.002) and hypertension (14.7 vs. 39.4%, p < 0.001) were significantly greater in the Obese cohort. Among unilateral reconstructions, postoperative length of stay (LOS) was longer among Obese patients (3.1 vs. 3.6 days, p = 0.016). Seroma occurred more frequently in Obese patients following bilateral reconstruction (5.7 vs. 0.0%, p = 0.047). Otherwise, there were no significant differences in complication rates between the groups. On multivariate analysis, BMI was not independently associated with complications, LOS, or operative time. CONCLUSION: The improvements in clinical and patient-reported outcomes that have been associated with postmastectomy breast reconstruction do not exclude obese women. This study indicates that microsurgical breast reconstruction can be performed safely and efficiently in patients with obesity.

Both Patients and Plastic Surgeons Prefer Artificial Intelligence-Generated Microsurgical Information.

BACKGROUND: With the growing relevance of artificial intelligence (AI)-based patient-facing information, microsurgical-specific online information provided by professional organizations was compared with that of ChatGPT (Chat Generative Pre-Trained Transformer) and assessed for accuracy, comprehensiveness, clarity, and readability. METHODS: Six plastic and reconstructive surgeons blindly assessed responses to 10 microsurgery-related medical questions written either by the American Society of Reconstructive Microsurgery (ASRM) or ChatGPT based on accuracy, comprehensiveness, and clarity. Surgeons were asked to choose which source provided the overall highest-quality microsurgical patient-facing information. Additionally, 30 individuals with no medical background (ages: 18-81, µ = 49.8) were asked to determine a preference when blindly comparing materials. Readability scores were calculated, and all numerical scores were analyzed using the following six reliability formulas: Flesch-Kincaid Grade Level, Flesch-Kincaid Readability Ease, Gunning Fog Index, Simple Measure of Gobbledygook Index, Coleman-Liau Index, Linsear Write Formula, and Automated Readability Index. Statistical analysis of microsurgical-specific online sources was conducted utilizing paired t-tests. RESULTS: Statistically significant differences in comprehensiveness and clarity were seen in favor of ChatGPT. Surgeons, 70.7% of the time, blindly choose ChatGPT as the source that overall provided the highest-quality microsurgical patient-facing information. Nonmedical individuals 55.9% of the time selected AI-generated microsurgical materials as well. Neither ChatGPT nor ASRM-generated materials were found to contain inaccuracies. Readability scores for both ChatGPT and ASRM materials were found to exceed recommended levels for patient proficiency across six readability formulas, with AI-based material scored as more complex. CONCLUSION: AI-generated patient-facing materials were preferred by surgeons in terms of comprehensiveness and clarity when blindly compared with online material provided by ASRM. Studied AI-generated material was not found to contain inaccuracies. Additionally, surgeons and nonmedical individuals consistently indicated an overall preference for AI-generated material. A readability analysis suggested that both materials sourced from ChatGPT and ASRM surpassed recommended reading levels across six readability scores.

Topical vanadate improves tensile strength and alters collagen organisation of excisional wounds in a mouse model.

Wound dehiscence, oftentimes a result of the poor tensile strength of early healing wounds, is a significant threat to the post-operative patient, potentially causing life-threatening complications. Vanadate, a protein tyrosine phosphatase inhibitor, has been shown to alter the organisation of deposited collagen in healing wounds and significantly improve the tensile strength of incisional wounds in rats. In this study, we sought to explore the effects of locally administered vanadate on tensile strength and collagen organisation in both the early and remodelling phases of excisional wound healing in a murine model. Wild-type mice underwent stented excisional wounding on their dorsal skin and were divided equally into three treatment conditions: vanadate injection, saline injection control and an untreated control. Tensile strength testing, in vivo suction Cutometer analysis, gross wound measurements and histologic analysis were performed during healing, immediately upon wound closure, and after 4 weeks of remodelling. We found that vanadate treatment significantly increased the tensile strength of wounds and their stiffness relative to control wounds, both immediately upon healing and into the remodelling phase. Histologic analysis revealed that these biomechanical changes were likely the result of increased collagen deposition and an altered collagen organisation composed of thicker and distinctly organised collagen bundles. Given the risk that dehiscence poses to all operative patients, vanadate presents an interesting therapeutic avenue to improve the strength of post-operative wounds and unstable chronic wounds to reduce the risk of dehiscence.

Complication Rates in Therapeutic Versus Prophylactic Bilateral Mastectomies: Insights From a National Database.

BACKGROUND: The "Jolie effect" and other media focus on prophylactic treatments have resulted in unilateral breast cancer patients increasingly undergoing contralateral prophylactic mastectomy. Little is known, however, regarding outcomes following therapeutic versus prophylactic mastectomy. In this study, we compared complication rates of unilateral breast cancer patients undergoing contralateral prophylactic mastectomy (BM-TP) to patients undergoing bilateral prophylactic mastectomy (BM-P). METHODS: The BM-TP and BM-P patients from 2015 to 2019 were identified in Optum Clinformatics DataMart. Six-month outcomes were assessed and included wound complications, infection, hematoma/seroma, breast pain, fat necrosis, flap failure, implant failure/removal, other flap/implant complications, and other complications. Multivariable regression models adjusted for age, residence, insurance, race, and Charlson Comorbidity Index score. RESULTS: Of 9319 women, 7114 (76.3%) underwent BM-TP, and 2205 (23.7%) underwent BM-P. In multivariable analysis, BM-TP had higher odds of overall complications (adjusted odds ratio [aOR], 1.35; P < 0.0001), but no difference was observed among patients who had autologous ( P = 0.1448) or no breast reconstruction ( P = 0.1530). Higher odds of overall complications persisted even after controlling for radiation therapy (aOR, 1.25; P = 0.0048) and chemotherapy (aOR, 1.28; P = 0.0047), but not after controlling for lymph node surgery ( P = 0.7765). CONCLUSION: The BM-TP (vs BM-P) patients face higher odds of overall complications but without any difference in certain reconstructive modalities or after controlling for lymph node surgery.

Understanding the Role of Adipocytes and Fibroblasts in Cancer.

ABSTRACT: Cancer is currently the second leading cause of death in the United States. There is increasing evidence that the tumor microenvironment (TME) is pivotal for tumorigenesis and metastasis. Recently, adipocytes and cancer-associated fibroblasts (CAFs) in the TME have been shown to play a major role in tumorigenesis of different cancers, specifically melanoma. Animal studies have shown that CAFs and adipocytes within the TME help tumors evade the immune system, for example, by releasing chemokines to blunt the effectiveness of the host defense. Although studies have identified that adipocytes and CAFs play a role in tumorigenesis, adipocyte transition to fibroblast within the TME is fairly unknown. This review intends to elucidate the potential that adipocytes may have to transition to fibroblasts and, as part of the TME, a critical role that CAFs may play in affecting the growth and invasion of tumor cells. Future studies that illuminate the function of adipocytes and CAFs in the TME may pave way for new antitumor therapies.

Technical Tips to Reduce Implant Rippling in Staged Pre-pectoral Breast Reconstruction.

INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) is becoming increasingly popular, permitting optimal implant positioning on the chest wall, prevention of animation deformity, and reduced patient discomfort. There are, however, concerns related to increased rates of breast implant rippling in pre-pectoral (versus submuscular) IBR, which can prompt a patient to seek revisionary surgery. The aim of this study is to identify factors that can be implemented to reduce implant rippling in the setting of pre-pectoral IBR. METHODS: A literature review was conducted using the PubMed database to determine the rate of rippling in pre-pectoral IBR. Clinical studies in English were included. Further review was then performed to explore technical strategies associated with reduced rates of rippling in pre-pectoral two-stage breast reconstruction. RESULTS: Implant rippling has been reported with a rate varying from 0 to 53.8% in 25 studies of pre-pectoral IBR (including both direct-to-implant and two-stage IBR). The majority of studies reviewed did not demonstrate a significant association between BMI and rippling, suggesting that other factors, likely technical and device-related, contribute to the manifestation of implant rippling. Hence, we explored whether specific technical modifications could be implemented that would reduce the risk of rippling in patients undergoing pre-pectoral IBR. Specifically, we highlight the need for close attention to expansion protocol and pocket dimension, expander fill medium and implant characteristics, and the rationale behind adjunctive procedures to reduce implant rippling. CONCLUSION: Surgical modifications may reduce the incidence of rippling in pre-pectoral breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin.

BACKGROUND: Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin. METHODS: Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions. RESULTS: Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds. CONCLUSION: Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

Lymphatic regeneration after implantation of aligned nanofibrillar collagen scaffolds: Preliminary preclinical and clinical results.

BACKGROUND: We tested our hypothesis that implantation of aligned nanofibrillar collagen scaffolds (BioBridge™) can both prevent and reduce established lymphedema in the rat lymphedema model. Our authors report clinical cases that demonstrate new lymphatic formation guided by BioBridge™ as seen by near-infrared (NIR) fluoroscopy and magnetic resonance (MR) lymphography. METHODS: A rat lymphedema model was utilized. A prevention group received implantation of BioBridge™ immediately after lymphadenectomy. A lymphedema group received implantation of BioBridge™ with autologous adipose-derived stem cells (ADSC; treatment group) or remained untreated (control group). All subjects were observed for 4 months after lymphadenectomy. The hindlimb change was evaluated using computed tomography-based volumetric analysis. Lymphagiogenesis was assessed by indocyanine green (ICG) lymphography. RESULTS: Animals in the treatment group showed a reduction in affected limb volume. Animals in the prevention group showed no increase in the affected limb volume. ICG fluoroscopy demonstrated lymph flow and formation of lymphatics toward healthy lymphatics. CONCLUSIONS: In the rat lymphedema model, implantation of BioBridge™ at the time of lymph node removal prevents the development of lymphedema. Treatment of established lymphedema with the BioBridge™ and ADSC reduces lymphedema. New lymphatic vessels are demonstrated by NIR fluoroscopy and MR lymphography. These findings have implications for the treatment of lymphedema in human subjects.

Perineal Reconstruction With the Profunda Artery Perforator Flap.

BACKGROUND: Abdominoperineal resection is used to treat a variety of colorectal pathologies. Traditionally, the vertical rectus abdominis myocutaneous flap has been most commonly used for reconstruction. Here, we explore the role of the profunda artery perforator (PAP) flap for perineal reconstruction. METHODS: A prospectively maintained database was retrospectively analyzed to identify patients who had undergone perineal reconstruction with a pedicled PAP flap. Parameters of interest included age, sex, body mass index, primary diagnosis, comorbidities, and history of radiation, and postoperative complications. RESULTS: Fifteen patients (5 men and 10 women) with a median age of 52 years (interquartile range, 48.5-61.5 years) were included in the study. Median body mass index was 26.3 kg/m2 (interquartile range, 24.0-29.3 kg/m2). Patients underwent abdominoperineal resection for treatment of rectal cancer (n = 9, 60.0%), recurrent anal squamous cell carcinoma (n = 3, 20.0%), and Crohn's disease (n = 3, 20.0%). Twelve patients (80.0%) underwent neoadjuvant radiotherapy. Eight patients (53.3%) experienced a total of 10 complications (2 major and 8 minor). The most common complication was donor (n = 3, 20.0%)/recipient (n = 3, 20.0%) site wound dehiscence. Stable soft tissue coverage was achieved in all patients. CONCLUSIONS: The PAP flap provides stable soft tissue coverage of perineal defects with a low donor-site morbidity. This flap should be strongly considered in the reconstructive algorithm when approaching perineal defects.

Nonsurgical Orthodontic Airway Plate Treatment for Newborns With Robin Sequence.

Despite promising outcomes for >50 years, nonsurgical orthodontic airway plates (OAP) are only infrequently offered for babies with Robin sequence in a few parts of the world. This article demonstrates possibility of providing functional improvement using an OAP to help these babies overcome their functional and structural difficulties on their own. Two consecutively treated cases are presented exemplifying that OAP treatment that had originated from Europe is reproducible and effective in an institution in the United States.

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.