In Vitro Culture of White Adipose Tissue.

White adipose tissue (WAT) plays a crucial endocrine organ that regulates blood glucose and lipid levels, satiety, and inflammation. Before the described technique, primary white adipocytes could not be stably cultured in vitro. The lack of a reliable primary culture model impeded research in WAT metabolism and drug development. We have developed a novel technique for WAT primary culture called "sandwiched white adipose tissue" (SWAT). SWAT overcomes the natural buoyancy of adipocytes by sandwiching minced WAT between sheets of adipose-derived stromal cells. The resulting constructs are viable for at least 8 weeks in culture. SWAT maintains the intact extracellular matrix, cell-to-cell contacts, and physical pressures of in vivo WAT conditions; additionally, SWAT maintains a robust transcriptional profile, sensitivity to exogenous chemical signaling, and whole tissue function. SWAT represents a simple, reproducible, and effective method of primary adipose culture. Potentially, it is a broadly applicable platform for research in WAT physiology, pathophysiology, metabolism, and pharmaceutical development.

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness. In validation studies, genetic disruption of CaMKK2 expression or inhibition of its activity with small molecule inhibitors disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor prognosis ovarian cancer subtype, shares many features with TNBC, and CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Mechanistically, CaMKK2 increased the expression of the phosphodiesterase PDE1A, which hydrolyzed cyclic guanosine monophosphate (cGMP) to decrease the cGMP-dependent activity of protein kinase G1 (PKG1). Inhibition of PKG1 resulted in decreased phosphorylation of vasodilator-stimulated phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate cell movement. Together, these findings establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis by impacting the actin cytoskeleton. Furthermore, it identifies CaMKK2 as a potential therapeutic target that can be exploited to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC. SIGNIFICANCE: CaMKK2 regulates actin cytoskeletal dynamics to promote tumor invasiveness and can be inhibited to suppress metastasis of breast and ovarian cancer, indicating CaMKK2 inhibition as a therapeutic strategy to arrest disease progression.

Ca 2+ /Calmodulin Dependent Protein Kinase Kinase-2 (CaMKK2) promotes Protein Kinase G (PKG)-dependent actin cytoskeletal assembly to increase tumor metastasis.

Triple-negative breast cancers (TNBCs) tend to become highly invasive early during cancer development. Despite some successes in the initial treatment of patients diagnosed with early-stage localized TNBC, the rate of metastatic recurrence remains high with poor long-term survival outcomes. Here we show that elevated expression of the serine/threonine-kinase, Calcium/Calmodulin (CaM)-dependent protein kinase kinase-2 (CaMKK2), is highly correlated with tumor invasiveness. We determined that genetic disruption of CaMKK2 expression, or inhibition of its activity, disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor-prognosis ovarian cancer subtype, shares many genetic features with TNBC, and importantly, CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Probing the mechanistic links between CaMKK2 and metastasis we defined the elements of a new signaling pathway that impacts actin cytoskeletal dynamics in a manner which increases cell migration/invasion and metastasis. Notably, CaMKK2 increases the expression of the phosphodiesterase PDE1A which decreases the cGMP-dependent activity of protein kinase G1 (PKG1). This inhibition of PKG1 results in decreased phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate contraction/cell movement. Together, these data establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis. Further, it credentials CaMKK2 as a therapeutic target that can be exploited in the discovery of agents for use in the neoadjuvant/adjuvant setting to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC.

Regenerative vs flap-based limb salvage: a multi-centered, prospective, randomized controlled trial.

Aim: The goal of this study was to compare success rates of a regenerative limb salvage approach (rLS) using dehydrated human chorion amnion membrane (dHACM) to traditional flap-based limb salvage (fLS). Materials & methods: This prospective RTC enrolled patients presenting with complex extremity wounds over a 3-year period. Primary outcomes included success of primary reconstruction, persistence of exposed structures, time to definitive closure, and time to weight bearing. Results: Patients meeting inclusion criteria were randomized to fLS (n = 14) or rLS (n = 25). The primary reconstructive method was successful for 85.7% of fLS subjects and 80% of rLS subjects (p = 1.00). Conclusion: This trial provides strong evidence that rLS is an effective option in the setting of complex extremity wounds, with success rates comparable to traditional flaps. Clinical Trial Registration: NCT03521258 (ClinicalTrials.gov).

Chronic and traumatic wounds may result in loss of limb without appropriate medical treatment. Traditionally large wounds with exposed bone or other important structures require surgery to transfer healthy soft tissue (a tissue flap) from one area of the body to the defect created by the wound. Our study seeks to demonstrate an approach to similar wounds using a biologic dressing to avoid extensive surgery. We demonstrate that this biologic dressing made from human membranes has a similar success rate to flap surgery for achieving wound healing.

The Impact of Exogenous Testosterone on Breast Cancer Risk in Transmasculine Individuals.

BACKGROUND: Exogenous testosterone is vital to gender-affirming therapy for transmasculine individuals. Testosterone may be implicated in breast cancer (BCa) because it can activate androgen and estrogen receptors. To further explore this risk, we performed a systematic review to investigate the impact of exogenous testosterone on BCa risk in transmasculine individuals. METHODS: We searched PubMed/MEDLINE and Ovid/Embase for clinical and preclinical studies assessing BCa and testosterone therapy and screened 6125 articles independently. We ascertained level of evidence using a modified tool from Cook et al (Chest. 1992;102:305S-311S) and risk of bias using a modified Joanna Briggs Institute's Critical Appraisal Tool. RESULTS: Seventy-six studies were included. Epidemiological data suggested that BCa incidence was higher in transmasculine individuals compared with cisgender men but lower compared with cisgender women. Histological studies of transmasculine breast tissue samples also demonstrated a low incidence of precancerous lesions. Interestingly, cases demonstrated that BCa occurred at a younger average age in transmasculine individuals and was predominantly hormone receptor positive. The mechanism for BCa in transmasculine individuals may be related to androgen receptor stimulation or conversion to estradiol. Serum studies reported varied estradiol levels associated with exogenous testosterone. Animal and in vitro studies demonstrated that testosterone was growth inhibitory but may induce proliferation at higher doses or with low estradiol levels. CONCLUSIONS: Plastic surgeons play a critical role in providing gender-affirming care for transmasculine patients. The limited studies available suggest that this patient population has decreased risk for BCa when compared with cisgender women; however, any BCa that does occur may have different clinical presentations and underlying mechanisms compared with cisgender women and men. Overall, the limitations for clinical studies and discrepancies among preclinical studies warrant further investigation.

Pilot study of minimally adherent silver dressings for acute surgical wounds.

Background and Aims: Minimally adherent silver dressings (SILVER MASD) are antimicrobial, nonirritating, provide a moist wound healing environment, and low cost. The purpose of this pilot, single-center, non-blinded randomized controlled trial was to quantify the outcomes of acute surgical wounds treated with MASD versus standard of care (SoC) dressings. Methods: Thirty-two patients with acute wounds were randomized 1:1 to be treated with MASD once weekly or SoC following surgical excision of skin and/or subcutaneous tissue between September 13, 2016 and November 28, 2017. The outcome variables included clinical infection, time to wound closure, and pain scores at dressing changes. Two independent, one-sided sample t-tests were performed to assess statistical significance. Results: There was no difference in wound healing between SILVER MASD and SoC. Dressing changes were less painful for wounds managed with MASD silver dressings. Conclusions: The results of this study suggest that MASD are not less effective in wound healing compared to SoC while also providing the benefit of decreased pain at dressing changes. Therefore, minimally adherent silver dressings can and should be considered a viable option in the management of acute surgical wounds.

Treatment of a recurrent ischial ulcer with injected exosomes.

Pressure ulcers (PUs) affect 2.5 million patients per year. Even after successful reconstruction, 50% of PUs recur. Patients with multiply recurrent PUs eventually consume all locoregional donor sites. This underscores the need for novel, less invasive approaches in PU reconstruction. Here, we report the first successful use of mesenchymal stem cell exosomes in PU reconstruction. The patient presented with a right ischial ulcer that persisted despite 9 months of wound care and appropriate antibiotic therapy. After six subcutaneous ExoFlo exosome injections over 8 weeks, the PU was completely healed. Additional studies of this promising technology should be performed.

Pilot phase results of a prospective, randomized controlled trial of narrowband ultraviolet B phototherapy in hospitalized COVID-19 patients.

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up to 8 consecutive days. Primary outcomes were safety and efficacy, defined as persistent or painful erythema and 28-day mortality. Comparisons were made via non-parametric exact tests. Patients in treatment (n = 15) and placebo (n = 15) arms had similar demographics. No adverse events occurred. Twenty eight-day mortality was 13.3% in treatment vs. 33.3% in placebo arms (p = 0.39). NB-UVB phototherapy in hospitalized COVID-19 patients was safe. Decreased mortality was observed in treated patients but this was statistically non-significant. Given its low-cost, scalability, and adjunctive nature, NB-UVB has the potential to improve COVID-19 outcomes. Continuation of this trial is warranted.

Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma.

BACKGROUND: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS. METHODS: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro. RESULTS: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR. CONCLUSIONS: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS.

Dehydrated Human Amniotic-Chorionic Membrane Reduces Incisional Hernia Formation in an Animal Model.

BACKGROUND: Currently there are no standard of care treatment strategies for IH prevention (IHP). Dehydrated human amnion-chorion (dHACM) is a healing adjunct that elutes growth factors including several that have reduced IH in animal models. We therefore performed a double-blinded, prospective randomized controlled trial (RCT) to test the hypothesis that dHACM significantly reduces IH formation in a well-studied animal model of acute IH. MATERIAL AND METHODS: Forty 16-week-old male Sprague-Dawley rats were randomized to one of four groups: No Treatment vs. dHACM Sheet (Group A), and Saline vs. dHACM Injection (Group B). Each animal underwent a 5-cm midline laparotomy which was incompletely closed with 5-0 plain gut sutures; this was performed by a surgeon blinded to treatment group (first blind). After 28 days, the primary endpoints of IH formation and hernia size were determined by study staff blinded to treatment (second blind). Secondary endpoints included healed fascia tensile strength as determined by tensiometry, systemic and local inflammatory markers as measured by ELISA, and fascial scar collagen I/III ratios per Western blotting. RESULTS: In Group A, No Treatment developed IH at 87.5% vs. 62.5% for Sheet (P = 0.28). Hernias that formed in the Sheet group were significantly smaller (P = 0.036). In Group B, Injection and Saline yielded identical IH rates of 77.8%. Molecular characterization of fascial scar demonstrated non-inferior tensile strength, collagen I/III ratios, and inflammatory markers in dHACM-treated animals. CONCLUSIONS: dHACM sheets significantly reduced the size of IH following laparotomy when compared to no treatment.

A Role for Adipocytes and Adipose Stem Cells in the Breast Tumor Microenvironment and Regenerative Medicine.

Obesity rates are climbing, representing a confounding and contributing factor to many disease states, including cancer. With respect to breast cancer, obesity plays a prominent role in the etiology of this disease, with certain subtypes such as triple-negative breast cancer having a strong correlation between obesity and poor outcomes. Therefore, it is critical to examine the obesity-related alterations to the normal stroma and the tumor microenvironment (TME). Adipocytes and adipose stem cells (ASCs) are major components of breast tissue stroma that have essential functions in both physiological and pathological states, including energy storage and metabolic homeostasis, physical support of breast epithelial cells, and directing inflammatory and wound healing responses through secreted factors. However, these processes can become dysregulated in both metabolic disorders, such as obesity and also in the context of breast cancer. Given the well-established obesity-neoplasia axis, it is critical to understand how interactions between different cell types in the tumor microenvironment, including adipocytes and ASCs, govern carcinogenesis, tumorigenesis, and ultimately metastasis. ASCs and adipocytes have multifactorial roles in cancer progression; however, due to the plastic nature of these cells, they also have a role in regenerative medicine, making them promising tools for tissue engineering. At the physiological level, the interactions between obesity and breast cancer have been examined; here, we will delineate the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment. We will define the current state of understanding of how adipocytes and ASCs contribute to tumor progression through their role in the tumor microenvironment and how this is altered in the context of obesity. We will also introduce recent developments in utilizing adipocytes and ASCs in novel approaches to breast reconstruction and regenerative medicine.

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System.

Breast cancer (BC) remains a leading cause of death for women. Despite more than $700 million invested in BC research annually, 97% of candidate BC drugs fail clinical trials. Therefore, new models are needed to improve our understanding of the disease. The NIH Microphysiological Systems (MPS) program was developed to improve the clinical translation of basic science discoveries and promising new therapeutic strategies. Here we present a method for generating MPS for breast cancers (BC-MPS). This model adapts a previously described approach of culturing primary human white adipose tissue (WAT) by sandwiching WAT between adipose-derived stem cell sheets (ASC)s. Novel aspects of our BC-MPS include seeding BC cells into non-diseased human breast tissue (HBT) containing native extracellular matrix, mature adipocytes, resident fibroblasts, and immune cells; and sandwiching the BC-HBT admixture between HBT-derived ASC sheets. The resulting BC-MPS is stable in culture ex vivo for at least 14 days. This model system contains multiple elements of the microenvironment that influence BC including adipocytes, stromal cells, immune cells, and the extracellular matrix. Thus BC-MPS can be used to study the interactions between BC and its microenvironment. We demonstrate the advantages of our BC-MPS by studying two BC behaviors known to influence cancer progression and metastasis: 1) BC motility and 2) BC-HBT metabolic crosstalk. While BC motility has previously been demonstrated using intravital imaging, BC-MPS allows for high-resolution time-lapse imaging using fluorescence microscopy over several days. Furthermore, while metabolic crosstalk was previously demonstrated using BC cells and murine pre-adipocytes differentiated into immature adipocytes, our BC-MPS model is the first system to demonstrate this crosstalk between primary human mammary adipocytes and BC cells in vitro.

Quantifying Breast Cancer-Driven Fiber Alignment and Collagen Deposition in Primary Human Breast Tissue.

Solid tumor progression is significantly influenced by interactions between cancer cells and the surrounding extracellular matrix (ECM). Specifically, the cancer cell-driven changes to ECM fiber alignment and collagen deposition impact tumor growth and metastasis. Current methods of quantifying these processes are incomplete, require simple or artificial matrixes, rely on uncommon imaging techniques, preclude the use of biological and technical replicates, require destruction of the tissue, or are prone to segmentation errors. We present a set of methodological solutions to these shortcomings that were developed to quantify these processes in cultured, ex vivo human breast tissue under the influence of breast cancer cells and allow for the study of ECM in primary breast tumors. Herein, we describe a method of quantifying fiber alignment that can analyze complex native ECM from scanning electron micrographs that does not preclude the use of replicates and a high-throughput mechanism of quantifying collagen content that is non-destructive. The use of these methods accurately recapitulated cancer cell-driven changes in fiber alignment and collagen deposition observed by visual inspection. Additionally, these methods successfully identified increased fiber alignment in primary human breast tumors when compared to human breast tissue and increased collagen deposition in lobular breast cancer when compared to ductal breast cancer. The successful quantification of fiber alignment and collagen deposition using these methods encourages their use for future studies of ECM dysregulation in human solid tumors.

Acellular Dermal Matrix-Associated Complications in Implant-Based Breast Reconstruction: A Multicenter, Prospective, Randomized Controlled Clinical Trial Comparing Two Human Tissues.

BACKGROUND: Implant-based breast reconstruction accounts for the vast majority of breast reconstruction procedures and is commonly performed with human acellular dermal matrix. There is no consensus as to the optimal human acellular dermal matrix preparation, and high-quality evidence concerning comparative effectiveness is lacking. This study is the first prospective, multicenter, randomized controlled clinical trial to compare human acellular dermal matrix-related complications of the two most commonly used human acellular dermal matrices in implant-based breast reconstruction. The authors hypothesize that there will be no difference in infection, seroma, and reconstructive failure between FlexHD Pliable and AlloDerm RTU. METHODS: The authors conducted a Level 1 prospective, randomized, controlled, multicenter clinical trial to assess complications associated with the use of two human acellular dermal matrices in immediate postmastectomy implant-based breast reconstruction across seven clinical sites. Group A patients received FlexHD Pliable (113 patients with 187 breast reconstructions), and group B patients received AlloDerm RTU (117 patients with 197 breast reconstructions). RESULTS: There was no significant difference with respect to patient demographics, indications, comorbidities, and reconstruction approach between groups. Mean follow-up time was 10.7 ± 3.2 months. There was no statistical difference in the overall matrix-related complications between groups A and B (4.3 percent versus 7.1 percent, p = 0.233). Obesity (OR, 1.14; 95 percent CI, 1.05 to 1.24; p = 0.001) and prepectoral placement of matrix (OR, 4.53; 95 percent CI, 1.82 to 11.3; p = 0.001) were independently associated with greater risks of overall matrix-related complications. CONCLUSION: This work supports the use of human acellular dermal matrices in implant-based breast reconstruction and demonstrates no significant difference in matrix-related complication rates between FlexHD Pliable and AlloDerm RTU. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

National health disparities in incisional hernia repair outcomes: An analysis of the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2012-2014.

BACKGROUND: Incisional hernias represent an acquired defect from failed healing of an abdominal facial incision and are therefore distinct from primary hernias. While literature regarding incisional hernia incidence, risk factors, and treatment are abundant, no study has examined national health disparities specific to incisional hernia repair. The objective of this study was to analyze national health disparities unique to surgical incisional hernia repair procedures. METHODS: Patient data queried from the Healthcare Cost and Utilization Project National Inpatient Sample from 2012 to 2014 using International Classification of Diseases 9th revision procedure codes for incisional hernia repair were used to generate univariate and multivariate models including demographics, socioeconomic factors, admission status, and hospital characteristics. Primary outcomes were nonelective admission status, in-hospital mortality, surgical complications, and extended duration of stay. RESULTS: We estimated that 89,258 incisional hernia repair procedures occurred annually from 2012 to 2014, incurring $6.3 billion in hospital charges. By multivariate analysis, multiple risk factors contribute to significantly increased odds of nonelective repair. These include age over 65, female sex, non-White race, nonprivate insurance, obesity, and increased Charlson comorbidity index. Nonelective incisional hernia repair was strongly correlated with worse outcomes including in-hospital mortality (odds ratio [95% confidence interval] 3.01 [2.51, 3.61]), postoperative complications (odds ratio 1.2 [1.14, 1.25]), and extended duration of stay (odds ratio 2.96 [2.81, 3.12]). After controlling for admission status, other disparities persisted including extended duration of stay for Black individuals (odds ratio 1.21 (1.12, 1.31]). CONCLUSION: Providers should be aware of these significant health disparities in incisional hernia repair status and outcomes especially for elderly, non-White, nonprivate insurance, and obese/comorbid patients. Management strategies that increase access to elective repair and that prevent incisional hernia should be expanded to address these disparities.

Health Disparities in Incisional Hernia Presentation : An Analysis of HCUP-NIS Years 2012-2014.

INTRODUCTION: Incisional hernias (IH) are iatrogenically created in 400 000 new patients annually. Without repair, IH-associated complications can result in major illness and death. The health disparities literature suggests that under-represented patients present more frequently with surgical emergencies. The health disparities associated with IH remain relatively unstudied. METHODS: Inpatient admission data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample for 2012-2014. Patients with IH International Classification of Diseases ninth revision were included. Analyses were completed using survey specific procedures (SAS v.9.4). Type of admission within groups was compared via Rao-Scott chi-square tests. The probability of an elective admission was modeled via SurveyLogistic Procedure. RESULTS: Of 39 296 cases, 38.5% IH admissions were urgent or emergent (nonelective). The proportion of nonelective admission was statistically higher (P < .0001) in patients >65 (40.9%) and females (40.3%). Among insurance types, self-paying patients had the highest proportion of nonelective admissions (64.3%). Racial disparities remained significant after adjusting for age, sex, and insurance. Compared with white patients, the odds of an admission being nonelective were significantly higher for black (odds ratio [OR] [95% CI]: 1.65 [1.53-1.77]], Hispanic (OR [95% CI]: 1.39 [1.28-1.51]), and other (OR [95% CI]: 1.2 [1.06-1.37]) patients. DISCUSSION: These data show that multiple at-risk patient populations are significantly more likely to require urgent admission for IH-related complications. These include older, female, non-white, and uninsured patients. Systematic efforts to ameliorate these disparities should be developed.

Prevalence of Accessory Branches and Other Anatomical Variations in the Radial Artery Encountered during Radial Forearm Flap Harvest: A Systematic Review and Meta-analysis.

BACKGROUND: Harvest of the radial forearm flap (RFF) for reconstructive surgery is proceeded by the Allen test to assess for adequate contralateral perfusion of the hand, yet the Allen test may fail to detect anatomical variations in the radial artery such as aberrant branching. Therefore, the goal of this study was to systematically review the literature regarding anatomical abnormalities of the radial artery that can affect flap harvest and to perform a meta-analysis to estimate the prevalence of such abnormalities. METHODS: A systematic review of the literature was conducted using five online databases to identify all instances of radial artery anatomical variations. Abstracts were reviewed and categorized into either (1) large cohort studies of anatomical variations identified by angiogram or (2) case reports specifically mentioning anomalous or accessory branches of the radial artery. Data from the large cohort studies were included in a random effect meta-analysis to estimate the prevalence of such variations. RESULTS: Eighteen angiogram cohort studies containing a total of 18,115 patients were included in the meta-analysis. Accessory branches were the least common anatomical variant reported, with an estimated average prevalence of 0.5%. Prevalence estimates for more common anatomical variants, including radial artery loops (0.9%), stenosis (1.3%), hypoplasia (1.9%), tortuosity (4.3%), and abnormal origin (5.6%), were also calculated. Thirteen case reports detailing anomalous branches of the radial artery were identified, seven of which involved accessory branches encountered during RFF harvest with no incidence of flap loss. CONCLUSION: Radial artery accessory branches are exceedingly rare, but the prevalence of other anatomical variations that can affect harvest of the RFF warrants consideration. We recommend surgeons consider comprehensive screening prior to RFF harvest to avoid intraoperative discovery of anatomical variants and suggest a low threshold for repeat perfusion testing intraoperatively if radial artery accessory branches are encountered.

Patient-Derived Xenografts as an Innovative Surrogate Tumor Model for the Investigation of Health Disparities in Triple Negative Breast Cancer.

Despite a decline in overall incidence rates for cancer in the past decade, due in part to impressive advancements in both diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer-related deaths in women. BC alone accounts for ∼30% of all new cancer diagnoses in women worldwide. Triple-negative BC (TNBC), defined as having no expression of the estrogen or progesterone receptors and no amplification of the HER2 receptor, is a subtype of BC that does not benefit from the use of estrogen receptor-targeting or HER2-targeting therapies. Differences in socioeconomic factors and cell intrinsic and extrinsic characteristics have been demonstrated in Black and White TNBC patient tumors. The emergence of patient-derived xenograft (PDX) models as a surrogate, translational, and functional representation of the patient with TNBC has led to the advances in drug discovery and testing of novel targeted approaches and combination therapies. However, current established TNBC PDX models fail to represent the diverse patient population and, most importantly, the specific ethnic patient populations that have higher rates of incidence and mortality. The primary aim of this review is to emphasize the importance of using clinically relevant translatable tumor models that reflect TNBC human tumor biology and heterogeneity in high-risk patient populations. The focus is to highlight the complexity of BC as it specifically relates to the management of TNBC in Black women. We discuss the importance of utilizing PDX models to study the extracellular matrix (ECM), and the distinct differences in ECM composition and biophysical properties in Black and White women. Finally, we demonstrate the crucial importance of PDX models toward novel drug discovery in this patient population.

Reconsidering the "MR Unsafe" breast tissue expander with magnetic infusion port: A case report and literature review.

Breast tissue expanders (TEs) with magnetic infusion ports are labeled "MR Unsafe." Therefore, patients with these implants are typically prevented from undergoing magnetic resonance imaging (MRI). We report a patient with a total submuscular breast TE who inadvertently underwent an MRI exam. She subsequently developed expander exposure, requiring explantation and autologous reconstruction. The safety profile of TEs with magnetic ports and the use of MRI in patients with these implants is surprisingly controversial. Therefore, we present our case report, a systematic literature review, and propose procedural guidelines to help ensure the safety of patients with TEs with magnetic ports that need to undergo MRI exams.