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 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.

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.

Health Insurance Portability and Accountability Act Noncompliance in Patient Photograph Management in Plastic Surgery.

BACKGROUND: Today, plastic surgeons have largely transitioned to digital photography. This shift has introduced new risks to daily workflows, notably data theft and Health Insurance Portability and Accountability Act (HIPAA) violations. METHODS: We performed a national survey of digital photograph management patterns among members of the American Society of Plastic Surgery and trainees in Accreditation Council for Graduate Medical Education-accredited plastic surgery programs. RESULTS: Our findings showed that attendings preferred the use of stand-alone digital cameras (91.4%), whereas trainees preferred the use of smartphones (96.1%) for capturing patient photographs. The rate of noncompliance was nearly identical; 82.8% of attendings were HIPAA noncompliant when using stand-alone digital cameras compared with 90.2% of trainees using smartphones. Both groups also breached HIPAA rules when using other photographic management modalities. CONCLUSIONS: This is the first study to quantify the prevalence of noncompliance with regard to an entire digital photograph management workflow. These findings were consistent with previous studies that reported that younger physicians tend to embrace newer technologies, whereas older attendings are more reluctant. The findings also suggest that HIPAA noncompliance in digital photograph security and management is a significant problem within the plastic surgery community.

Phentermine: A Systematic Review for Plastic and Reconstructive Surgeons.

PURPOSE: Phentermine is the most prescribed antiobesity drug in America, with 2.43 million prescriptions written in 2011. Case reports suggest there are anesthetic risks, such as refractory hypotension, involved with its perioperative use. Despite these risks and the frequency of phentermine use among plastic surgery patients, there are no published guidelines for the perioperative management of phentermine use in the plastic surgery literature. To address this patient safety issue, we performed a systematic review and provide management recommendations. METHODS: A systematic review of the pharmacology of phentermine and the anesthetic risks involved with its perioperative use was undertaken using the search engines PubMed/MEDLINE, EMBASE, and Scopus. RESULTS: A total of 251 citations were reviewed, yielding 4 articles that discussed perioperative phentermine use and complications with anesthesia. One was a review article, 2 were case reports, and 1 was a letter. Complications included hypotension, hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and acute pulmonary edema. CONCLUSIONS: The relationship between phentermine and anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is the most reported complication of perioperative phentermine use. Specifically, phentermine-induced hypotension may be unresponsive to vasopressors that rely on catecholamine release, such as ephedrine. Therefore, the decision to perform surgery, especially elective surgery, in a patient taking phentermine should be made with caution. Because of the half-life of phentermine, we recommend discontinuing phentermine for at least 4 days prior to surgery. This differs from the classic 2-week discontinuation period recommended for "fen-phen." The patient should be made aware of the increased risk of surgery, and a skilled anesthesiologist should monitor intraoperative blood pressure and body temperature for signs of autonomic derailment.

Variations in the Anterolateral Thigh Flap's Vascular Anatomy in African Americans.

BACKGROUND: Variations in anterolateral thigh (ALT) arterial anatomy are well documented. Ethnicity is a known risk factor for vascular variation in several organ systems, but its impact on ALT anatomy has not been studied. Anecdotally, we observed frequent ALT arterial variation in African American (AA) patients. We thus hypothesized that AA patients have higher rates of anomalous branching. MATERIALS AND METHODS: A total of 277 computed tomography angiograms (513 lower extremities) captured between May 1, 2013 and May 31, 2015 at a tertiary academic medical center were retrospectively analyzed to determine ALT arterial branching. Patient records were examined to ascertain demographics. Data were analyzed using descriptive statistics and multinomial logistic regression. RESULTS: Males comprised 84.5%. Ethnic distribution was 55.2% AA and 36.5% Caucasian. The descending branch of the lateral circumflex femoral artery (dLCFA) originated from non-LCFA arteries (deep femoral, common femoral, or superficial femoral arteries) in 18.9% of Caucasian versus 9.1% of AA (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.33-3.93, p < 0.01). An oblique branch was identified in 41.1% of Caucasian versus 51.9% of AA (OR: 1.56; 95% CI: 1.08-2.24, p = 0.02). Ethnicity was the only driving factor of dLCFA and oblique branch of the LCFA (oLCFA) anatomy (Wald chi-square: 14 and 11, p = 0.03 and 0.02, respectively). CONCLUSIONS: Ethnicity significantly affects ALT arterial anatomy. AA are more likely to have classical dLCFA branching with a fourth oLCFA branch. A flap with an unrecognized oLCFA-dominant supply places patients at a higher risk for flap failure and loss. We recommend preoperative imaging before undertaking an ALT flap reconstruction.

The Sternum-Nipple Distance is Double the Nipple-Inframammary Fold Distance in Macromastia.

BACKGROUND: Reduction mammaplasty is one of the most commonly performed plastic surgery operations. For a majority of techniques, the most common long-term complication is pseudoptosis. It has previously been proposed that upper breast suspensory ligaments (SL) are weaker than lower breast SL. We tested this hypothesis through anthropometry of the proxies for upper and lower SL strength: the sternal notch-nipple (SN-N) distance and the nipple-inframammary fold (N-IMF) distance, respectively. METHODS: An institutional review board-approved retrospective review of patients undergoing reduction mammoplasty in an academic faculty practice between 2008 and 2015 was conducted. Patient demographics included age, race, and body mass index (BMI); patient comorbidities included smoking status, diabetes, and hypertension. Breast anthropometric measurements included SN-N and N-IMF. Sternal notch-nipple was used as the primary metric of the upper SL strength, whereas N-IMF was used as the primary metric of the lower SL strength. Intraoperative details included reduction technique and resection mass. Postoperative complications were recorded, including nipple areola complex necrosis and hematoma. Linear regression analysis was performed with the primary endpoint of the relationship between SN-N and N-IMF distance in macromastia. RESULTS: Data from 208 patients, totaling 400 individual breast measurements, were collected. The mean SN-N length was 35.1 cm, mean N-IMF length was 16.0 cm, and mean resection weight was 1094 g. Linear regression found that N-IMF distance could be predicted as 45% of the SN-N distance (N-IMF = 0.454 * SN-N). This was a strong relationship, demonstrated by univariate analysis of SN-N and N-IMF (R, 0.624; P < 0.001). A Wise pattern was used in 89.9% of cases; an inferior pedicle was used in 83.7% of cases. Nipple areola complex necrosis occurred in 15 breasts (3.75%). Sternal notch-nipple (R, 0.127; P = 0.011) and N-IMF (R, 0.119; P = 0.017) were both predictive of nipple areola complex necrosis (Table 4). CONCLUSIONS: In our series, the N-IMF distance increased 0.45 cm for every 1 cm increase in the SN-N distance. This relationship strengthens our primary hypothesis that the lower pole ligaments stretch at a significantly slower rate than the upper pole ligaments. Taking this into consideration, we suggest that surgeons seeking to minimize pseudoptosis rates should favor techniques that minimally disrupt the lower SL.

A Time Study of Plastic Surgery Residents.

BACKGROUND: Resident work hours are under scrutiny and have been subject to multiple restrictions. The studies supporting these changes have not included data on surgical residents. We studied the workday of a team of plastic surgery residents to establish prospective time-study data of plastic surgery (PRS) residents at a single tertiary-care academic medical center. METHODS: Five trained research assistants observed all residents (n = 8) on a PRS service for 10 weeks and produced minute-by-minute activity logs. Data collection began when the team first met in the morning and continued until the resident being followed completed all non-call activities. We analyzed our data from 3 perspectives: 1) time spent in direct patient care (DPC), indirect patient care, and didactic activities; 2) time spent in high education-value activities (HEAs) versus low education-value activities; and 3) resident efficiency. We defined HEAs as activities that surgeons must master; other activities were LEAs. We quantified resident efficiency in terms of time fragmentation and time spent waiting. RESULTS: A total of 642.4 hours of data across 50 workdays were collected. Excluding call, residents worked an average of 64.2 hours per week. Approximately 50.7% of surgical resident time was allotted to DPC, with surgery accounting for the largest segment of this time (34.8%). Time spent on HEAs demonstrated trended upward with higher resident level (P = 0.086). Time in spent in surgery was significantly associated with higher resident levels (P < 0.0001); 57.7% of activities require 4 minutes or less, suggesting that resident work was highly fragmented. Residents spent 10.7% of their workdays waiting for other services. CONCLUSIONS: In this first-time study of PRS residents, we found that compared with medicine trainees, surgical residents spent 3.23 times more time on DPC. High education-value activities comprised most of our residents' workdays. Surgery was the leading component of both DPC and HEAs. Our residents were highly efficient and fragmented, with the majority of all activities requiring 4 minutes or less. Residents spent a large portion of their time waiting for other services. In light of these data, we suggest that future changes to residency programs be pilot tested, with preimplantation and postimplementation time studies performed to quantify the changes' impact.

Wound healing in acutely injured fascia.

Fascial healing following acute injury, such as that occurring during surgical procedures, is defined functionally. For example, failure of fascial healing following celiotomy is only identified when incisional hernias are diagnosed. Such hernias incur billions of dollars per year in medical costs. Despite the importance of fascial healing, there is a paucity of data regarding the quality such healing. In clinical settings, the quantification of fascial wound healing is limited to a binary state: either there is no clinically apparent functional deficit and full fascia healing is assumed, or an incisional hernia or other functional failure is visible and the fascia did not heal. There are no clinical methods to isolate and functionally test fascia in patients. Recent studies have revealed unexpected findings regarding the recovery of tensile strength, specific surgical methods that optimize fascial healing, and the potential impact of biological pharmaceuticals in eliminating fascial healing failure. However, much remains unknown about the biology of fascial healing.

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.

Local Control of Pyoderma Gangrenosum Using Human Amniotic Membrane and Transcriptome Analysis.

Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative disease characterized by non-healing wounds that worsen with debridement, a phenomenon called pathergy. No consensus regarding pathogenesis, diagnosis, or treatment exists for PG. A previous pilot study using dehydrated human amniotic/chorionic membrane (dHACM), following excisional debridement, augmented PG wound healing and allowed for subsequent wound closure through split-thickness skin grafting (STSG). In this clinical trial (NCT05120726), four patients with an established PG diagnosis were enrolled to undergo treatment with dHACM and characterize the pre- and post-treatment transcriptome profiles. RNA sequencing was used to isolate the total RNA from specimens. Genes of particular interest were quantified through real-time quantitative reverse transcription polymerase chain reaction. We observed varied changes to the local expression of inflammatory response, positive regulators of cellular proliferation, and extracellular matrix disassembly cytokines. All PG wounds produced granulation tissue following treatment and were closed using split-thickness skin grafts.

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.

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.

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.

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.

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.