A tension offloading patch mitigates dermal fibrosis induced by pro-fibrotic skin injections.

Skin fibrosis is a clinical problem with devastating impacts but limited treatment options. In the setting of diabetes, insulin administration often causes local dermal fibrosis, leading to a range of clinical sequelae including impeded insulin absorption. Mechanical forces are important drivers of fibrosis and, clinically, physical tension offloading at the skin level using an elastomeric patch significantly reduces wound scarring. However, it is not known whether tension offloading could similarly prevent skin fibrosis in the setting of pro-fibrotic injections. Here, we develop a porcine model using repeated local injections of bleomycin to recapitulate key features of insulin-induced skin fibrosis. Using histologic, tissue ultrastructural, and biomechanical analyses, we show that application of a tension-offloading patch both prevents and rescues existing skin fibrosis from bleomycin injections. By applying single-cell transcriptomic analysis, we find that the fibrotic response to bleomycin involves shifts in myeloid cell dynamics from favoring putatively pro-regenerative to pro-fibrotic myeloid subtypes; in a mechanomodulatory in vitro platform, we show that these shifts are mechanically driven and reversed by exogenous IL4. Finally, using a human foreskin xenograft model, we show that IL4 treatment mitigates bleomycin-induced dermal fibrosis. Overall, this study highlights that skin tension offloading, using an FDA cleared, commercially available patch, could have significant potential clinical benefit for the millions of patients dependent on insulin.

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.

Direct-to-Implant versus Immediate Free Flap Reconstruction after Nipple-Sparing Mastectomy: A Propensity Score-Matched Analysis.

BACKGROUND: Both direct-to-implant (DTI) and immediate free flap (FF) breast reconstruction following nipple-sparing mastectomy (NSM) have been described in the literature. However, there is a paucity of comparative studies between these two techniques. Furthermore, existing studies do not control for factors influencing ischemic complications. METHODS: A retrospective review of all NSMs performed at a single institution between January of 2014 and January of 2020 was performed. Immediate FF reconstructions were propensity score matched using probit regression to identify a comparable DTI cohort based on mastectomy weight, smoking, age, and history of radiotherapy. Primary outcomes of interest were 30-day ischemic complications. RESULTS: One hundred eight NSMs performed in 79 patients were included. Average age was 45.7 ± 10.5 years and mean body mass index was 27.1 ± 4.8 kg/m 2 . There were 54 breasts in both the DTI group and the immediate FF group. Median mastectomy weight in the DTI group was 508 g (interquartile range, 264 g) as compared with 473 g (interquartile range, 303 g) in the FF group ( P = 0.792). There was no significant difference in the rate of partial nipple-areola complex necrosis in the DTI and FF groups (5.6% versus 3.7%, respectively; P = 0.500) or mastectomy flap necrosis (5.6% versus 11.1%; P = 0.297). Both the DTI and FF groups had a total nipple-areola complex necrosis rate of 1.9% ( P = 0.752). CONCLUSION: Both DTI and immediate FF reconstruction can be safely offered to patients undergoing NSM while providing the benefit of a single reconstructive procedure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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.

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.

Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting.

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

Fat Grafts Augmented With Vitamin E Improve Volume Retention and Radiation-Induced Fibrosis.

BACKGROUND: Treatments for radiation-induced fibrosis range from vitamin E (VE) and pentoxifylline (PTX) systemically to deferoxamine and fat grafting locally. Regarding fat grafting, volume retention hinders its long-term functionality and is affected by 2 factors: inflammation and necrosis secondary to hypovascularity. OBJECTIVE: The authors aimed to simultaneously improve fat graft retention and radiation-induced fibrosis by integrating VE and PTX into fat grafts locally. METHODS: Forty adult CD-1 nude male mice, 6 weeks old, underwent scalp irradiation and recovered for 4 weeks to allow for development of fibrosis. Mice received 200 µL of donor human fat graft to the scalp. Mice were separated into 4 conditions: no grafting, fat graft without treatment, graft treated with PTX, and graft treated with VE. Fat graft volume retention was monitored in vivo with micro-computed tomography scans at weeks 0, 1, 2, 4, 6, and 8 after grafting. Histological and cytokine analysis of the scalp skin and fat grafts were performed. RESULTS: VE-treated grafts had significant improvement in dermal thickness and collagen density of overlying skin compared with all other groups. VE decreased 8-isoprostane and increased CD31+ staining compared with the other grafted groups. Cytokine analysis revealed decreased inflammatory and increased angiogenic markers in both the fat graft and overlying skin of the VE group. Fat graft volume retention was significantly improved in the VE group starting at 1 week post grafting. CONCLUSIONS: Radiation-induced fibrosis and fat graft volume retention are both simultaneously improved with local administration of VE.

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.

Standardizing Dimensionless Cutometer Parameters to Determine In Vivo Elasticity of Human Skin.

Objective: Skin fibrosis places an enormous burden on patients and society, but disagreement exists over methods to quantify severity of skin scarring. A suction cutometer measures skin elasticity in vivo, but it has not been widely adopted because of inconsistency in data produced. We investigated variability of several dimensionless parameters generated by the cutometer to improve their precision and accuracy. Approach: Twenty adult human subjects underwent suction cutometer measurement of normal skin (NS) and fibrotic scars (FS). Using Mode 1, each subject underwent five trials with each trial containing four curves. R0/2/5/6/7 and Q1/2/3 data were collected. Analyses were performed on these calculated parameters. Results: R0/2/5/6/7 and Q1/2 parameters from curves 1 to 4 demonstrated significant differences, whereas these same parameters were not significantly different when only using curves 2-4. Individual analysis of all parameters between curve 1 and every subsequent curve was statistically significant for R0, R2, R5, R6, R7, Q1, and Q2. No differences were appreciated for parameter Q3. Comparison between NS and FS were significantly different for parameters R5, Q1, and Q3. Innovation: Our study is the first demonstration of accurate comparison between NS and FS using the dimensionless parameters of a suction cutometer. Conclusions: Measured parameters from the first curve of each trial were significantly different from subsequent curves for both NS and FS. Precision and reproducibility of data from dimensionless parameters can therefore be improved by removing the first curve. R5, Q1, and Q3 parameters differentiated NS as more elastic than FS.

Readability of Online Patient Information Relating to Cleft Palate Surgery.

OBJECTIVE: It is important for health care education materials to be easily understood by caretakers of children requiring craniofacial surgery. This study aimed to analyze the readability of Google search results as they pertain to "Cleft Palate Surgery" and "Palatoplasty." Additionally, the study included a search from several locations globally to identify possible geographic differences. DESIGN: Google searches of the terms "Cleft Palate Surgery" and "Palatoplasty" were performed. Additionally, searches of only "Cleft Palate Surgery" were run from several internet protocol addresses globally. MAIN OUTCOME MEASURES: Flesch-Kincaid Grade Level and Readability Ease, Gunning Fog Index, Simple Measure of Gobbledygook (SMOG) index, and Coleman-Liau Index. RESULTS: Search results for "Cleft Palate Surgery" were easier to read and comprehend compared to search results for "Palatoplasty." Mean Flesch-Kincaid Grade Level scores were 7.0 and 10.11, respectively (P = .0018). Mean Flesch-Kincaid Reading Ease scores were 61.29 and 40.71, respectively (P = .0003). Mean Gunning Fog Index scores were 8.370 and 10.34, respectively (P = .0458). Mean SMOG Index scores were 6.84 and 8.47, respectively (P = .0260). Mean Coleman-Liau Index scores were 12.95 and 15.33, respectively (P = .0281). No significant differences were found in any of the readability measures based on global location. CONCLUSIONS: Although some improvement can be made, craniofacial surgeons can be confident in the online information pertaining to cleft palate repair, regardless of where the search is performed from. The average readability of the top search results for "Cleft Palate Surgery" is around the seventh-grade reading level (US educational system) and compares favorably to other health care readability analyses.

Decellularized Adipose Matrices Can Alleviate Radiation-Induced Skin Fibrosis.

Objective: Radiation therapy is commonplace for cancer treatment but often results in fibrosis and atrophy of surrounding soft tissue. Decellularized adipose matrices (DAMs) have been reported to improve these soft tissue defects through the promotion of adipogenesis. These matrices are decellularized by a combination of physical, chemical, and enzymatic methods to minimize their immunologic effects while promoting their regenerative effects. In this study, we aimed at exploring the regenerative ability of a DAM (renuva®; MTF biologics, Edison, NJ) in radiation-induced soft tissue injury. Approach: Fresh human lipoaspirate or DAM was injected into the irradiated scalp of CD-1 nude mice, and volume retention was monitored radiographically over 8 weeks. Explanted grafts were histologically assessed, and overlying skin was examined histologically and biomechanically. Irradiated human skin was also evaluated from patients after fat grafting or DAM injection. However, integrating data between murine and human skin in all cohorts is limited given the genetic variability between the two species. Results: Volume retention was found to be greater with fat grafts, though DAM retention was, nonetheless, appreciated at irradiated sites. Improvement in both mouse and human irradiated skin overlying fat and DAM grafts was observed in terms of biomechanical stiffness, dermal thickness, collagen density, collagen fiber networks, and skin vascularity. Innovation: This is the first demonstration of the use of DAMs for augmenting the regenerative potential of irradiated mouse and human skin. Conclusions: These findings support the use of DAMs to address soft tissue atrophy after radiation therapy. Morphological characteristics of the irradiated skin can also be improved with DAM grafting.

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.

A comparative analysis of deferoxamine treatment modalities for dermal radiation-induced fibrosis.

The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation-induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD-1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post-recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS-detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

Angiogenic CD34+CD146+ adipose-derived stromal cells augment recovery of soft tissue after radiotherapy.

Radiation therapy is effective for cancer treatment but may also result in collateral soft tissue contracture, contour deformities, and non-healing wounds. Autologous fat transfer has been described to improve tissue architecture and function of radiation-induced fibrosis and these effects may be augmented by enrichment with specific adipose-derived stromal cells (ASCs) with enhanced angiogenic potential. CD34+CD146+, CD34+CD146-, or CD34+ unfractionated human ASCs were isolated by flow cytometry and used to supplement human lipoaspirate placed beneath the scalp of irradiated mice. Volume retention was followed radiographically and fat grafts as well as overlying soft tissue were harvested after eight weeks for histologic and biomechanical analyses. Radiographic evaluation revealed the highest volume retention in fat grafts supplemented with CD34+CD146+ ASCs, and these grafts were also found to have greater histologic integrity than other groups. Irradiated skin overlying CD34+CD146+ ASC-enriched grafts was significantly more vascularized than other treatment groups, had significantly less dermal thickness and collagen deposition, and the greatest improvement in fibrillin staining and return of elasticity. Radiation therapy obliterates vascularity and contributes to scarring and loss of tissue function. ASC-enrichment of fat grafts with CD34+CD146+ ASCs not only enhances fat graft vascularization and retention, but also significantly promotes improvement in overlying radiation-injured soft tissue. This regenerative effect on skin is highly promising for patients with impaired wound healing and deformities following radiotherapy.

Prevention and Management of Complications of Tissue Flaps.

In this article, we discuss 4 common free flaps performed in reconstructive surgery: the anterolateral thigh flap, the radial forearm flap, the fibula flap, and the transverse rectus abdominis myocutaneous/deep inferior epigastric perforator flap. Donor and recipient complications for each flap type and strategies on how to prevent and manage such complications are discussed.

The Adrenergic System in Plastic and Reconstructive Surgery: Physiology and Clinical Considerations.

ABSTRACT: The primary organ systems and tissues concerning plastic and reconstructive surgery include the integument, vasculature, subcutis, and peripheral nerves, because these may individually or collectively be injured requiring reconstruction, or indeed be used in reconstruction themselves through grafts, flaps, or anastomoses. Adrenergic receptors are present throughout these anatomic components on the vasculature, adipose, platelets, immune cells, keratinocytes, melanocytes, fibroblasts, peripheral nerves, and tendons. Herein, the influence of adrenergic signaling on the physiology of anatomic components related to plastic surgery is discussed, along with clinical considerations of this systems involvement in procedures, such as free flap reconstruction, skin grafting, fat grafting, and other areas relevant to plastic and reconstructive surgery. Current evidence as well as potential for further investigation is discussed.

Intraoperative Invasive Blood Pressure Monitoring in Flap-Based Breast Reconstruction: Does It Change Outcomes?

Despite the lack of guidelines regarding the use of intra-arterial lines in postmastectomy breast reconstruction (PMBR), they continue to be used in this setting. In this study of patients undergoing PMBR, we aimed to (1) identify factors associated with intra-arterial line placement, (2) analyze the correlation between intra-arterial monitoring and noninvasive blood pressure (NIBP) monitoring, and (3) investigate whether hemodynamic management differs significantly between patients undergoing intra-arterial blood pressure monitoring versus NIBP. METHODS: All patients undergoing flap-based PMBR between 2017 and 2019 were retrospectively reviewed. Patients were pair-matched based on flap donor site, BMI, and age to identify factors associated with intra-arterial line placement. Methods described by Bland and Altman1 were utilized to determine agreement between intra-arterial line measurements and NIBP. RESULTS: Thirty-two patients were included with 16 patients in the intra-arterial line group and 16 in the NIBP group. None of the factors studied were significantly related to the likelihood of intra-arterial line placement. Agreement analysis demonstrated that mean arterial pressures calculated from intra-arterial line readings were as much as 23 points lower or 12 points higher than those from NIBP. Bias calculations with this extent of difference suggest poor correlation between intra-arterial line readings and NIBP. There was no difference between groups in rate of administration of blood-pressure altering medications (hypertensive: n = 3, 18.8%, P = 1.000; hypotensive: n = 7, 3.8%, P = 1.000). CONCLUSION: Our findings highlight the need for more definitive guidance regarding the use of intra-arterial monitoring in patients undergoing PMBR.

Chronic Pain Following Cosmetic Breast Surgery: A Comprehensive Review.

INTRODUCTION: Cosmetic breast surgery is commonly performed in the United States; 520,000 procedures of the total 1.8 million cosmetic surgical procedures performed in 2018 were breast related. Postoperative chronic pain, defined as lasting 3 or more months, has been reported in a wide variety of breast surgical procedures including breast augmentation, reduction mammaplasty, mastectomy, and mastectomy with reconstruction. Patient characteristics associated with the development of postoperative chronic pain following cosmetic breast surgery include a younger age, larger BMI, smaller height, postoperative hyperesthesia, and elevated baseline depression, anxiety, and catastrophizing scores. The anatomical distribution of chronic pain following breast augmentation procedures is dependent upon incision site placement; pectoral and intercostal nerves have been implicated. The purpose of this review is to provide an update on the current literature addressing the pathophysiology, clinical presentation, and treatment of patients presenting with chronic postoperative pain following cosmetic breast surgery. METHODS: A comprehensive literature review was performed in MEDLINE, PubMed, and Cochrane databases from 1996 to 2019 using the terms "cosmetic surgery", "breast surgery", "postoperative pain", and "chronic pain". RESULTS: Cosmetic breast surgery can have a similar presentation as post-mastectomy pain syndrome and thus have overlapping diagnostic criteria. Seven domains are identified for a diagnosis of PBSPS: Pain after breast surgery, neuropathic in nature, at least a moderate intensity of pain, as defined as within the middle one-third of the selected pain scale, pain for at least 6 months, symptoms occurring for 12 or more hours a day for a minimum of 4 days each week, pain in at least one of the following sites: breast, chest wall, axilla, or arm on the affected side, pain exacerbated by movement. Patient risk factors and surgical risk factors may influence the development of chronic post-cosmetic surgery breast pain. Improved perioperative analgesia including preoperative regional nerve anesthesia and postoperative catheter infusion have been shown to improve chronic postoperative pain outcomes. CONCLUSIONS: The present review provides a discussion of clinical presentation, pathophysiology, and treatment and preventative strategies for chronic breast pain following cosmetic surgery. This review provides evidence from multiple randomized controlled trials (RCTs) and systematic reviews of efficacy and effectiveness. While chronic postoperative breast pain remains challenging to treat, various preventative strategies have been described to improve postoperative pain outcomes.

Fully automated analysis of OCT imaging of human kidneys for prediction of post-transplant function.

Current measures for assessing the viability of donor kidneys are lacking. Optical coherence tomography (OCT) can image subsurface tissue morphology to supplement current measures and potentially improve prediction of post-transplant function. OCT imaging was performed on donor kidneys before and immediately after implantation during 169 human kidney transplant surgeries. A system for automated image analysis was developed to measure structural parameters of the kidney's proximal convoluted tubules (PCTs) visualized in the OCT images. The association of these structural parameters with post-transplant function was investigated. This study included kidneys from live and deceased donors. 88 deceased donor kidneys in this study were stored by static cold storage (SCS) and an additional 15 were preserved by hypothermic machine perfusion (HMP). A subset of both SCS and HMP deceased donor kidneys were classified as expanded criteria donor (ECD) kidneys, with elevated risk of poor post-transplant function. Post-transplant function was characterized as either immediate graft function (IGF) or delayed graft function (DGF). In ECD kidneys stored by SCS, increased PCT lumen diameter was found to predict DGF both prior to implantation and following reperfusion. In SCD kidneys preserved by HMP, reduced distance between adjacent lumen following reperfusion was found to predict DGF. Results suggest that OCT measurements may be useful for predicting post-transplant function in ECD kidneys and kidneys stored by HMP. OCT analysis of donor kidneys may aid in allocation of kidneys to expand the donor pool as well as help predict post-transplant function in transplanted kidneys to inform post-operative care.