Search

IntroductionBreast reconstruction plays an important role for many in restoring form and function of the breast after mastectomy. However, rates of breast reconstruction in the USA vary significantly by race, ethnicity and socioeconomic status. The lower rates of breast reconstruction in non-white women and in women of lower socioeconomic status may reflect a complex interplay between patient and physician factors and access to care. It remains unknown what community-specific barriers may be impacting receipt of breast reconstruction.Methods and analysisThis is a mixed-methods study combining qualitative patient interview data with quantitative practice patterns to develop an actionable plan to address disparities in breast reconstruction in the local community. The primary aims are to (1) capture barriers to breast reconstruction for patients in the local community, (2) quantitatively evaluate practice patterns at the host institution and (3) identify issues and prioritise interventions for change using community-based engagement.Ethics and disseminationEthics approval was obtained at the investigators’ institution. Results from both the quantitative and qualitative portions of the study will be circulated via peer-review publication. These findings will also serve as pilot data for extramural funding to implement and evaluate these proposed solutions.

BACKGROUND: Women of color with breast cancer are less likely to undergo post-mastectomy reconstruction compared with White women, but it is unclear whether their perioperative outcomes are worse. The goal of this study was to investigate differences in preoperative comorbidities and postoperative complications by race/ethnicity among women with breast cancer undergoing postmastectomy reconstruction. STUDY DESIGN: Data were collected from the National Inpatient Sample database of the Healthcare Cost and Utilization Project from 2012 to 2016. Patient demographics, types of reconstruction, comorbid conditions, Charlson-Deyo Combined Comorbidity (CDCC) scores, length of stay (LOS), and perioperative complications were abstracted. Multivariate linear and logistic regression were performed to model LOS and likelihood of postoperative complications, respectively. RESULTS: Compared with White women (n = 19,730), Black women (n = 3,201) underwent autologous reconstruction more frequently (40.7% vs 28.3%), had more perioperative comorbidities (eg diabetes: 12.9% vs 5.8%), higher CDCC scores (% CDCC ≥ 4: 5.5% vs 2.7%), and longer LOS (median 3 vs 2 days, all p < 0.001). Being Black (vs white: +0.13 adjusted days, 95% CI 0.06 to 0.19) was also associated with longer LOS and an increased likelihood of surgical complications (vs White: odds ratio 1.24, 95% CI 1.09 to 1.42, both p < 0.01), but this association did not persist when outcomes were limited to microsurgical complications. CONCLUSION: Disparities in postmastectomy breast reconstruction between Black and White women extend beyond access to care and include perioperative factors and outcomes. These findings suggest an important opportunity to mitigate inequities in reconstruction through perioperative health optimization and improved access to and co-management with primary care.

Purpose: Adipose tissue constitutes a significant volume of the breast. However its influence on breast cancer initiation remains poorly understood. Breast adipose stromal cells (breast ASCs), essential progenitors of breast fat tissue, are abundant in breast adipose tissue. We studied the biology of primary human bASCs and their contribution to the tumor microenvironment.Methods: We generated a bASC cell repository from women undergoing prophylactic or therapeutic mastectomies (n=6 breast cancer patients; n=2 high risk patients). bASCs were isolated from the stromal vascular fraction of breast adipose tissue. Senescence was measured in bASCs using the senescence-associated beta-galactosidase detection kit. Senescence-associated-cytokines and chemokines in conditioned media collected from bASCs were measured by ELISA. The ability of bASCs to support cytokine signaling was determined by immunoblotting. Adipogenic potential of bASCs was determined by AdipoRed staining.Results: bASCs from 63% (5/8) of women in our cohort scored positive for senescence, with only some secreting senescence-associated cytokines (IL-6; TGF-beta) and chemokines (IL-8). Only in select cases was bASC secretion of cytokine associated with their ability to support cytokine-specific signaling pathways (e.g. TGFb/Smad2 signaling). bASCs from 38% (3/8) of these women exhibited an adipogenesis defect, and 2/3 (67%) also scored positive for senescence.Conclusion: bASC biology shows notable biologic variability in women undergoing prophylactic or therapeutic mastectomies, with some exhibiting a senescent phenotype, some exhibiting an adipogenesis defect, and some supporting TGFb or IL-6 signaling. Our results establish an important foundation for larger studies examining the impact of aberrant bASC biologies on breast cancer risk.

INTRODUCTION As a profession, plastic surgeons must meet the public demand for aesthetic and reconstructive procedures. Patients search for physicians using Google, which offers insights into patient needs through their search history. METHODS The Google Trends Relative Search Volumes (RSV) were pulled for all searches for “plastic surgery” over 12 months. The number of active plastic surgeons per state was divided by Census Bureau population estimates to calculate the surgeons-per-capita value, or “surgical concentration.” The Google score divided by this concentration yields a “surgical demand index” for each state. RESULTS Florida, New York, and Connecticut had the greatest concentration of surgeons per ten-thousand people (0.220, 0.217, and 0.209, respectively), while Wyoming, Arkansas, and Vermont had the smallest (0.051, 0.071, 0.080). California exhibited the greatest number of Google searches (RSV=100), followed by Florida and Hawaii (RSV=95). Oregon (RSV=38), Virginia (RSV=52), and Alaska (RSV=58) had the fewest searches. The “surgical demand index” was greatest in Wyoming (1187.778), Oklahoma (993.751), and Arkansas (974.664) and smallest in Oregon (264.682), Virginia (320.716), and Connecticut (354.872). CONCLUSION The distribution of US plastic surgeons is not homogeneous. The Google data suggest that some markets (e.g. Oregon) are saturated while others (e.g. Wyoming) have significant demand that is not met by the number of plastic surgeons in those states.

Complications from breast reconstruction may delay postmastectomy radiation therapy and impact breast cancer outcomes. The authors hypothesized that immediate breast reconstruction may be associated with delays in the initiation of radiation, but that this delay would not significantly impact overall patient survival.Using the National Cancer Database, the authors identified women with breast cancer who underwent mastectomy and received postmastectomy radiation therapy. Delayed radiation was defined as treatment initiated 6 months or more after surgery in patients who received adjuvant chemotherapy or 12 weeks or more after surgery in patients who received neoadjuvant or no chemotherapy.Women undergoing breast reconstruction had an increased time to postmastectomy radiation therapy, 154 days versus 132 days (p0.001), and were more likely to experience a delay in initiating radiation (OR, 1.25; 95 percent CI, 1.188 to 1.314). Other factors associated with delayed radiation included increased Charlson/Deyo scores, neoadjuvant chemotherapy, nonprivate insurance, and black race. Cox proportional hazards models revealed no evidence of a reduced adjusted overall survival in the immediate breast reconstruction group (hazard ratio, 0.836; 95 percent CI, 0.802 to 0.871; p0.001). Restricted cubic spline analysis identified the threshold number of days at which the start of radiation began to impact survival at 169 days (95 percent CI, 160 to 190 days), 75 days (95 percent CI, 42 to 90 days), and 71 days (95 percent CI, 41 to 90 days) in patients undergoing adjuvant, neoadjuvant, and no chemotherapy, respectively.Immediate breast reconstruction is associated with a modest delay in initiating postmastectomy radiation therapy but does not impact overall survival.Therapeutic, III.

The tumor microenvironment within the breast is rich in adipose elements. The interaction between adipose cells and breast cancer is poorly understood, particularly as it pertains to patients with genetic susceptibility to breast cancer. This study focuses on the phenotype of human adipose-derived stem cells with the BRCA1 mutation and the effect they may have on breast cancer cell behavior.CRISPR/Cas9 was used to generate de novo BRCA1-knockdown human adipose-derived stem cells. The effect of the BRCA1 knockdown on the adipose-derived stem cell phenotype was compared to wild-type adipose-derived stem cells and patient-derived breast adipose-derived stem cells with known BRCA1 mutations. Interactions between adipose-derived stem cells and the MDA-MB-231 breast cancer cell line were evaluated.BRCA1-knockdown adipose-derived stem cells stimulated MDA-MB-231 proliferation (1.4-fold increase on day 4; p = 0.0074) and invasion (2.3-fold increase on day 2; p = 0.0171) compared to wild-type cells. Immunofluorescence staining revealed higher levels of phosphorylated ataxia telangiectasia-mutated activation in BRCA1-knockdown cells (72.9 ± 5.32 percent versus 42.9 ± 4.97 percent; p = 0.0147), indicating higher levels of DNA damage. Beta-galactosidase staining demonstrated a significantly higher level of senescence in BRCA1-knockdown cells compared with wild-type cells (7.9 ± 0.25 percent versus 0.17 ± 0.17 percent; p0.0001). Using quantitative enzyme-linked immunosorbent assay to evaluate conditioned media, the authors found significantly higher levels of interleukin-8 in BRCA1-knockdown cells (2.57 ± 0.32-fold; p = 0.0049).The authors show for the first time that the BRCA1 mutation affects the adipose-derived stem cell phenotype. Moreover, CRISPR/Cas9-generated BRCA1-knockdown adipose-derived stem cells stimulate a more aggressive behavior in breast cancer cells than wild-type adipose-derived stem cells. This appears to be related to increased inflammatory cytokine production by means of a DNA damage-mediated cell senescence pathway.

Purpose Most triple-negative breast cancer (TNBC) patients exhibit an incomplete response to neoadjuvant chemotherapy, resulting in chemo-residual tumor cells that drive tumor recurrence and patient mortality. Accordingly, strategies for eliminating chemo-residual tumor cells are urgently needed. Although stromal cells contribute to tumor cell invasion, to date, their ability to influence chemo-residual tumor cell behavior has not been examined. Our study is the first to investigate cross-talk between adipose-derived stem cells (ASCs) and chemo-residual TNBC cells. We examine if ASCs promote chemo-residual tumor cell proliferation, having implications for tumor recurrence. Methods ASC migration toward chemo-residual TNBC cells was tested in a transwell migration assay. Importance of the SDF-1α/CXCR4 axis was determined using neutralizing antibodies and a small molecule inhibitor. The ability of ASCs to drive tumor cell proliferation was analyzed by culturing tumor cells ± ASC conditioned media (CM) and determining cell counts. Downstream signaling pathways activated in chemo-residual tumor cells following their exposure to ASC CM were studied by immunoblotting. Importance of FGF2 in promoting proliferation was assessed using an FGF2-neutralizing antibody. Results ASCs migrated toward chemo-residual TNBC cells in a CXCR4/SDF-1α-dependent manner. Moreover, ASC CM increased chemo-residual tumor cell proliferation and activity of extracellular signal-regulated kinase (ERK). An FGF2-neutralizing antibody inhibited ASC-induced chemo-residual tumor cell proliferation. Conclusions ASCs migrate toward chemo-residual TNBC cells via SDF-1α/CXCR4 signaling, and drive chemo-residual tumor cell proliferation in a paracrine manner by secreting FGF2 and activating ERK. This paracrine signaling can potentially be targeted to prevent tumor recurrence.

Purpose: Our laboratory studies contributions of breast adipose stromal cells (bASCs) to breast cancer initiation and progression. To date, most studies of ASC biology have focused on abdominal ASCs. We hypothesize that bASC biology impacts the breast microenvironment in a manner that influences a woman’s risk of developing breast cancer. Methods: In order to better understand how aberrant bASC biology contributes to breast cancer, we built a bASC cell repository from women undergoing mastectomies at Duke University Hospital (Duke IRB Pro00100739). Some of these women are at high risk for developing breast cancer. High risk biology includes women with genetic predispositions to cancer, as well as obese and post-menopausal women. bASCs were isolated from the stromal vascular fraction of breast adipose tissue from patients. Additionally, commercially-available ASCs isolated from the abdomen were obtained from Zenbio. Senescence was measured in bASCs using the SPiDER beta gal senescence detection kit (Dojingo). Senescence-associated cytokines were measured in conditioned media collected from these bASCs by ELISA (R&D Systems). The ability of bASCs to differentiate into adipocytes was measured using the Adipo-Red adipocyte differentiation assay (Lonza). Results: To date, we have isolated bASCs from 16 patients undergoing mastectomies at Duke University Hospital. We have studied differences in the biology of these bASCs that may be associated with increased breast cancer risk. A commonality observed in high risk patients was senescence, demonstrated by bASCs undergoing growth arrest and secretion of beta-galactosidase. Similarly, bASCs from high risk patients demonstrated secretion of inflammatory cytokines such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Interleukin-1beta (IL-1 beta) that are associated with the senescence-associated secretory phenotype. We hypothesize that the secretion by these bASCs of such cytokines creates an inflammatory breast microenvironment that increases breast cancer risk. Our data also indicate that bASCs from high risk patients exhibit a defect in their ability to differentiate into adipocytes. Conclusion: Our studies are the first to report on a repository of breast ASCs (bASCs) from patients undergoing mastectomies. Results indicate that bASC biology differs significantly amongst patients, with a subset exhibiting a senescent secretory phenotype associated with a block in their ability to differentiate into adipocytes. We hypothesize bASC senescence, associated with a senescence secretory phenotype, results in: 1) the inability of these bASCs to differentiate into adipocytes, and 2) a senescence-associated secretory phenotype that impacts the breast tumor microenvironment. As we continue to build the repository, studies are in progress to test if inflammatory cytokines secreted by senescent bASCs work in a paracrine fashion on breast epithelium to drive breast cancer initiation/ progression.

Breast cancer survival continues to improve, with women living longer after treatment. It is not well understood how long-term satisfaction and well-being differ following treatment or how types of reconstruction differ when compared to the norm.In a propensity-matched sample, the authors compared patient-reported outcomes in breast cancer patients at various time intervals from surgery with normative BREAST-Q data. All data were obtained using the Army of Women, an online community fostering breast cancer research. Breast cancer patients were stratified by surgical treatment and reconstruction type. Regression lines were estimated and differences in slope tested between cancer patients and noncancer controls.The authors compared normative (n = 922) and breast cancer (n = 4343) cohorts in a propensity-matched analysis. Among the breast cancer patients, 49.4 percent underwent lumpectomy, 17.0 percent underwent mastectomy, 21.7 percent underwent implant reconstruction, and 11.9 percent underwent autologous reconstruction. Median time since surgery was 4.7 years, with 21.1 percent more than 10 years after surgery. At the time of survey, breast cancer patients reported higher Satisfaction with Breasts and Psychosocial Well-being scores compared to noncancer controls (p0.01), with the cohorts undergoing lumpectomy and autologous reconstruction both reporting higher scores than the normative controls. After mastectomy, scores averaged lower than the noncancer controls, but improved over time. However, all breast cancer groups reported significantly lower Physical Well-being scores than the noncancer cohort (all p0.01).Breast cancer patients undergoing lumpectomy or autologous reconstruction reported higher psychosocial well-being compared to noncancer controls. These differences were influenced both by time since treatment and by choice of surgical procedure.

The American Society of Plastic Surgeons commissioned a multistakeholder Work Group to develop recommendations for autologous breast reconstruction with abdominal flaps. A systematic literature review was performed and a stringent appraisal process was used to rate the quality of relevant scientific research. The Work Group assigned to draft this guideline was unable to find evidence of superiority of one technique over the other (deep inferior epigastric perforator versus pedicled transverse rectus abdominis musculocutaneous flap) in autologous tissue reconstruction of the breast after mastectomy. Presently, based on the evidence reported here, the Work Group recommends that surgeons contemplating breast reconstruction on their next patient consider the following: the patient's preferences and risk factors, the setting in which the surgeon works (academic versus community practice), resources available, the evidence shown in this guideline, and, equally important, the surgeon's technical expertise. Although theoretical superiority of one technique may exist, this remains to be reported in the literature, and future methodologically robust studies are needed.

Bridget M Crawford,1,2,* Ronnie L Shammas,3,* Andrew M Fales,1,2 David A Brown,4 Scott T Hollenbeck,4 Tuan Vo-Dinh,1,2,5 Gayathri R Devi6,7 1Fitzpatrick Institute for Photonics, Duke University, 2Department of Biomedical Engineering, Duke University, 3Duke University School of Medicine, 4Department of Surgery, Division of Plastic, Maxillofacial, and Oral Surgery, Duke University Medical Center, 5Department of Chemistry, Duke University, 6Department of Surgery, Division of Surgical Sciences, 7Duke Cancer Institute, Women’s Cancer Program, Duke University School of Medicine, Durham, NC, USA *These authors contributed equally to this work Abstract: Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%–30% in case of women with stage III–IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model. Keywords: inflammatory breast cancer, photothermal therapy, hyperthermia, plasmonics, gold nanostars, nanoparticles

Introduction: Due to the aggressive nature of inflammatory breast cancer (IBC) and insensitive imaging techniques, patients diagnosed with IBC have a poor prognosis. IBC's unique ability to form emboli leads to rapid growth and distant invasion. New therapies aimed at disrupting the formation of tumor emboli are needed. Gold nanostars (GNS) are unique nanoparticles that can be imaged in real time with high sensitivity, and are rapidly endocytosed into cancer cells. Due to their sharp spikes, GNS exhibit plasmonic properties, which strongly enhance the electromagnetic field upon laser excitation. In addition to their use as highly intense and stable fluorescent labels, these nanoparticles can be photothermally activated to trigger cellular ablation. The use of GNS as an imaging and therapeutic modality for IBC should be investigated. Methods: IBC (SUM-149/SUM190), non-IBC (BT474M1/MD-MBA-231), and drug resistant isotype variant (rSUM-149) cell lines were incubated with GNS, stained with Hoechst33342, and imaged with multiphoton microscopy (MPM). The dose and time dependent effects of GNS on SUM-149 proliferation was assessed with MTT assays. Photothermal treatment was performed on GNS-labeled IBC, non-IBC, and drug resistant cancer cell lines. The effects of photothermal therapy on cell viability were assessed using fluorescein diacetate and propidium iodide. Using a tumor emboli model, SUM-149, rSUM-149, and SUM-190 tumor emboli were labeled with GNS on the 3rd day of embolic maturation. Emboli were sectioned, stained with H/E, and imaged with MPM to demonstrate the depth of GNS penetrance. The potential for photothermal ablation of the GNS-labeled tumor emboli was assessed using various laser intensities. Propidium iodide was used to examine emboli viability following treatment. Results: In all cell lines, GNS displayed rapid cellular uptake without nuclear involvement. MTT assay showed that GNS concentrations of 0.15 and 0.20 nM caused decreases in cell proliferation at 6 and 12 hours. Proliferative capacity was unaltered at 24 hours for all concentrations, however this may be due to spectrophotometric interference with high intracellular GNS concentrations. Live/dead staining confirmed effective photothermal treatment in all cultures with a clear zone of cellular death. For tumor emboli studies, GNS allowed bright fluorescent monitoring of tumor emboli using MPM, and cross sectional imaging demonstrated GNS penetrance into the embolic core. Photothermal ablation of GNS-labeled tumor emboli was successfully demonstrated following laser irradiation. Cell death was confirmed with propidium iodide. Conclusion: Gold nanostars provide a highly fluorescent intracellular label for cancer cell lines, and tumor emboli without significantly altering cell proliferation. Furthermore, the inherent optical properties of the GNS allows for a combined therapeutic application following phototoactivation. This is the first study to demonstrate the nanothernostic application of GNS in IBC tumor emboli. Prior studies have shown the effectiveness of photothermal ablation in in vivo sarcoma models; we are currently extending our studies to an IBC mouse model. Supported by the P30 Cancer Center Support Grant (GRD) and Duke Exploratory Funds (TVD). Citation Format: Shammas RL, Fales AM, Crawford BM, Hollenbeck ST, Vo-Dinh T, Devi GR. Nanotheranostics using plasmonic gold nanostars to target inflammatory breast cancer cells and tumor emboli [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-16-02.

Background:. With growing concerns about the overuse of contralateral prophylactic mastectomy, optimizing unilateral mastectomy reconstruction outcomes becomes a priority. However, there remains a paucity of objective data that describe volumetric symmetry between a natural and autologous-reconstructed breast. Methods:. We evaluated patients who underwent unilateral mastectomy reconstruction with free-flap abdominal tissue transfer from 04/2006 to 01/2015, and had at least 2 postoperative magnetic resonance images (MRIs; n = 28). Using these MRI data, volumetric measurements of the reconstructed and natural breast were performed at the first postoperative MRI (after all revisions were complete) and the most recent MRI. Relationships were analyzed using Spearman correlation coefficients. A symmetry score (SS) was calculated such that values closer to 1.0 reflected volumetric symmetry. Results:. The mean age (years) and BMI of the patients was 44.8 and 26.8, respectively. The mean interval time between the MRIs was 3.03 years (range 0.43–6.6). After surgical revisions were complete, volumetric symmetry between reconstructed and nonreconstructed breasts was typically achieved (mean SS 0.92). This symmetry was also retained at the end of follow-up (mean SS 0.96), despite a mean change in BMI of 3.9% (range 1.1–7.7). Additionally, the mean number of flap revisions was 0.75 (range 0–2), and 39% of patients had a procedure performed on the natural breast. Conclusion:. In patients undergoing unilateral abdominal-based breast reconstruction, volumetric symmetry is attainable; however, it can require flap revisions and procedures to natural breast. Interestingly, this study does show that initial symmetry is retained postoperatively, regardless of changes in BMI.

BACKGROUND: Despite increasing emphasis on reducing racial disparities in breast cancer care in the United States, it remains unknown whether access to breast reconstruction has improved over time. The authors characterized contemporary patterns of breast reconstruction by race and ethnicity. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify women undergoing mastectomy for stage 0 to III breast cancer from 1998 to 2014. Multivariable logistic regression was used to estimate the association of demographic factors with likelihood of postmastectomy reconstruction. Multivariable logistic regression was used to predict reconstruction subtype. Patients undergoing reconstruction were grouped by diagnosis year to assess change in the population over time by race and ethnicity. RESULTS: Of 346,418 patients, 21.8 percent underwent immediate reconstruction. Non-Hispanic black race (OR, 0.71) and Hispanic ethnicity (OR, 0.63) were associated with a decreased likelihood of reconstruction (all p < 0.001). Race was predictive of reconstruction type, with non-Hispanic black (OR, 1.52) and Hispanic women (OR, 1.22) more likely to undergo autologous versus implant-based reconstruction (p < 0.001). Although rates of reconstruction increased over time across all races, non-Hispanic black and Hispanic patients had a higher adjusted per-year increase in rate of reconstruction compared with non-Hispanic white patients (interaction p < 0.001). CONCLUSIONS: Rates of postmastectomy reconstruction have increased more quickly over time for minority women compared with white women, suggesting that racial disparities in breast reconstruction may be improving. However, race continues to be associated with differences in types and rates of reconstruction. Further research is necessary to continue to improve access to breast reconstruction in the United States. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Open tibia fractures are often associated with considerable soft tissue injuries. Management of open tibia fractures can be challenging, and some patients require amputation. The patient and treatment factors have not been described on a population level in the United States. A retrospective analysis was completed using the 2000 to 2011 Nationwide Inpatient Sample. Amputation rates during the index hospitalization after open tibia fracture were computed based on injury, patient, and hospital characteristics in patients 18 years or older. The overall amputation rate in open tibia fractures during the index hospitalization was 2.2% (n=3769). Patients with midshaft tibia fractures comprised the largest portion of patients undergoing amputation (46.8% of total amputations) compared with distal tibia (34.0%) and proximal tibia (19.3%) fractures. Patients with no neurovascular injury comprised the largest portion of patients undergoing amputation (85.9%), followed by isolated arterial injury (11.1%), combined neurovascular injury (1.9%), and isolated nerve injury (1.1%). Amputation rates were significantly increased for midshaft tibia fractures with neurovascular injury (odds ratio, 12.39; 95% CI, 5.52–27.83) and distal tibia fractures with neurovascular injury (odds ratio, 5.45; 95% CI, 1.73–17.19) compared with tibia fractures with no neurovascular injury while controlling for confounders. On the basis of a review of the Nationwide In-patient Sample during the past decade, the authors have shown that the early amputation rate in open tibia fractures for all-comers is 2.2%. Rates of amputation varied based on fracture site, associated neurovascular injury, medical comorbidities, and hospital location. [ Orthopedics . 2021;44(1):48–53.]

Background:. Advances in fracture fixation and soft tissue coverage continue to improve the care of patients after limb-threatening lower extremity (LE) trauma. However, debate continues regarding which treatment option—reconstruction or amputation—is most appropriate. Many authors have attempted to quantify the patient experience in this treatment paradigm; however, they have not used patient-reported outcome (PRO) instruments specific to this population. Our aim was to identify and evaluate PRO instruments developed specifically for LE trauma, applicable to reconstruction and amputation, using established PRO instrument development and validation guidelines. Methods:. A multidisciplinary team used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method to query PubMed, Medline Ovid, EMBASE, Cochrane, Medline Web of Science, and Psych Info databases from inception to November 2016. Publications were included that described the development and/or validation of a PRO instrument assessing satisfaction and/or quality of life in LE trauma, applicable to both amputation and reconstruction. Two authors independently reviewed each full-text citation. Results:. After removing duplicates, 6,290 abstracts were identified via the database query. Following a preliminary title and abstract screen, 657 full-text citations were reviewed. Of these references, none satisfied the previously established inclusion criteria. Conclusions:. No studies were identified that described a PRO instrument developed to assess outcomes in LE trauma patients applicable to both reconstruction and amputation. There is thus a need for a PRO instrument designed specifically for patients who have sustained limb-threatening LE trauma to guide treatment decisions.

Background A current limitation in the care of patients with severe lower extremity traumatic injuries is the lack of a rigorously developed patient-reported outcome (PRO) instrument specific to lower extremity trauma patients. Objective This mixed methods protocol aims to describe phases I and II of the development of a PRO instrument for lower extremity trauma patients, following international PRO development guidelines. Methods The phase I study follows an interpretive description approach. Development of the PRO instrument begins with identifying the concepts that are important to patients, after which a preliminary conceptual framework is devised from a systematic literature review and used to generate an interview guide. Patients aged 18 years or above with limb-threatening lower extremity traumatic injuries resulting in reconstruction, amputation, or amputation after failed reconstruction will be recruited. The subjects will participate in semistructured, in-depth qualitative interviews to identify all important concepts of interest. The qualitative interview data will be coded with top-level domains, themes, and subthemes. The codes will then be utilized to refine the conceptual framework and generate preliminary items and a set of scales. The preliminary scales will be further refined via a process of conducting cognitive debriefing interviews with lower extremity trauma patients and soliciting expert opinions. Phase III will include a large-scale field test, using Rasch measurement theory to analyze the psychometric properties of the instrument; shortening and finalizing the scales; and determining the reliability, validity, and responsiveness of the instrument. Results Phases I and II of this study have been funded. Phase I of this study has been completed, and phase II began in January 2019 and is expected to be completed in November 2019. Phase III will begin following the completion of phase II. Conclusions This protocol describes the initial phases of development of a novel PRO instrument for use in lower extremity trauma patients. International Registered Report Identifier (IRRID) DERR1-10.2196/14397

IMPORTANCE: An increasing number of patients with breast cancer receiving neoadjuvant chemotherapy (NACT) undergo immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) as surgical treatment. However, the oncologic efficacy and safety of this treatment sequencing strategy is unclear. OBJECTIVE: To compare the long-term oncologic outcomes of IBR with NSM/SSM and conventional mastectomy (CM) alone for breast cancer in the NACT setting. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, propensity score–matched case-control study was conducted at Asan Medical Center, Seoul, Korea. A total of 1266 patients with breast cancer who underwent NACT followed by mastectomy with or without breast reconstruction between January 1, 2010, and November 30, 2016, were included. Data analysis was performed from July 1, 2019, to January 24, 2020. After propensity score matching, 323 patients who underwent IBR with NSM/SSM and 323 who underwent CM alone were selected for comparison of long-term oncologic outcomes. MAIN OUTCOMES AND MEASURES: The 5-year local recurrence–free survival, disease-free survival, distant metastasis–free survival, and overall survival rates were calculated using the Kaplan-Meier method and compared using log-rank tests. Hazard ratios (HRs) and 95% CIs were estimated using the Cox proportional hazards regression model. RESULTS: After matching, the median follow-up periods were 67 (range, 17-125) months for the IBR group and 68 (range, 17-126) months for the CM-alone group. Median age of the women in the IBR group was 42 (range, 23-72) years; median age of those in the CM-alone group was 46 (range, 30-75) years. No significant differences were observed between the IBR and CM-alone groups in local recurrence (3.7% vs 3.4%; P = .83), regional recurrence (7.1% vs 5.3%; P = .33), or distant metastasis (17.3% vs 18.6%; P = .68) rates. There was also no significant difference between the IBR and CM-alone groups in 5-year local recurrence–free survival (95.6% vs 96.7%; HR, 1.124; 95% CI, 0.495-2.549; P = .78), disease-free survival (76.5% vs 79.9%; HR, 1.089; 95% CI, 0.790-1.500; P = .60), distant metastasis–free survival (82.5% vs 82.5%; HR, 0.941; 95% CI, 0.654-1.355; P = .74), or overall survival (92.0% vs 89.3%; HR, 0.847; 95% CI, 0.530-1.353; P = .49) rates. CONCLUSIONS AND RELEVANCE: The long-term oncologic outcomes of IBR with NSM/SSM for breast cancer in this study appeared to be comparable to those of CM alone after NACT, suggesting the feasibility of IBR with NSM/SSM in the NACT setting.

Background Craniomaxillofacial (CMF) fractures are typically treated with open reduction and internal fixation. Open reduction and internal fixation can be complicated by hardware exposure or infection. The literature often does not differentiate between these 2 entities; so for this study, we have considered all hardware exposures as hardware infections. Approximately 5% of adults with CMF trauma are thought to develop hardware infections. Management consists of either removing the hardware versus leaving it in situ. The optimal approach has not been investigated. Thus, a systematic review of the literature was undertaken and a resultant evidence-based approach to the treatment and management of CMF hardware infections was devised. Materials and methods A comprehensive search of journal articles was performed in parallel using MEDLINE, Web of Science, and ScienceDirect electronic databases. Keywords and phrases used were maxillofacial injuries; facial bones; wounds and injuries; fracture fixation, internal; wound infection; and infection. Our search yielded 529 articles. To focus on CMF fractures with hardware infections, the full text of English-language articles was reviewed to identify articles focusing on the evaluation and management of infected hardware in CMF trauma. Each article's reference list was manually reviewed and citation analysis performed to identify articles missed by the search strategy. There were 259 articles that met the full inclusion criteria and form the basis of this systematic review. The articles were rated based on the level of evidence. There were 81 grade II articles included in the meta-analysis. Result Our meta-analysis revealed that 7503 patients were treated with hardware for CMF fractures in the 81 grade II articles. Hardware infection occurred in 510 (6.8%) of these patients. Of those infections, hardware removal occurred in 264 (51.8%) patients; hardware was left in place in 166 (32.6%) patients; and in 80 (15.6%) cases, there was no report as to hardware management. Finally, our review revealed that there were no reported differences in outcomes between groups. Conclusions Management of CMF hardware infections should be performed in a sequential and consistent manner to optimize outcome. An evidence-based algorithm for management of CMF hardware infections based on this critical review of the literature is presented and discussed.

Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics.To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar-labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells.Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar-labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models.Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar-labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.

The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II–IV ovarian cancer. We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold. The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5–10 years after ovarian cancer diagnosis. For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.

Acellular dermal matrices (ADM) are commonly used in reconstructive procedures and rely on host cell invasion to become incorporated into host tissues. We investigated different approaches to adipose-derived stem cells (ASCs) engraftment into ADM to enhance this process. Lewis rat adipose-derived stem cells were isolated and grafted (3.0 × 105 cells) to porcine ADM disks (1.5 mm thick × 6 mm diameter) using either passive onlay or interstitial injection seeding techniques. Following incubation, seeding efficiency and seeded cell viability were measured in vitro. In addition, Eighteen Lewis rats underwent subcutaneous placement of ADM disk either as control or seeded with PKH67 labeled ASCs. ADM disks were seeded with ASCs using either onlay or injection techniques. On day 7 and or 14, ADM disks were harvested and analyzed for host cell infiltration. Onlay and injection techniques resulted in unique seeding patterns; however cell seeding efficiency and cell viability were similar. In-vivo studies showed significantly increased host cell infiltration towards the ASCs foci following injection seeding in comparison to control group (p < 0.05). Moreover, regional endothelial cell invasion was significantly greater in ASCs injected grafts in comparison to onlay seeding (p < 0.05). ADM can successfully be engrafted with ASCs. Interstitial engraftment of ASCs into ADM via injection enhances regional infiltration of host cells and angiogenesis, whereas onlay seeding showed relatively broad and superficial cell infiltration. These findings may be applied to improve the incorporation of avascular engineered constructs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:2939–2947, 2013.