Anna Luan

All Publications

• Automatic Detection of Perilunate and Lunate Dislocations on Wrist Radiographs Using Deep Learning. Plastic and reconstructive surgery Pridgen, B., von Rabenau, L., Luan, A., Gu, A. J., Wang, D. S., Langlotz, C., Chang, J., Do, B. 2023

  Abstract

  Delayed or missed diagnosis of perilunate or lunate dislocations can lead to significant morbidity. Advances in computer vision provide an opportunity to improve diagnostic performance. In this study, a deep learning algorithm was utilized for detection of perilunate and lunate dislocations on lateral wrist radiographs. A total of 435 lateral wrist radiographs were labeled as normal or pathologic (perilunate or lunate dislocation). The lunate in each radiograph was segmented with a rectangular bounding box. Images were partitioned into training and test sets. Two neural networks, consisting of an object detector followed by an image classifier, were applied in series. First, the object detection module was used to localize the lunate. Next, the image classifier performed a binary classification for normal or pathologic. The accuracy, sensitivity, and specificity of the overall system were evaluated. A receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) were used to demonstrate the overall performance of the computer vision algorithm. The lunate object detector was 97.0% accurate at identifying the lunate. Accuracy was 98.7% among the sub-group of normal wrist radiographs, and 91.3% among the sub-group of wrist radiographs with perilunate/lunate dislocations. The perilunate/lunate dislocation classifier had a sensitivity (recall) of 93.8%, specificity of 93.3%, and accuracy of 93.4%. The AUC was 0.986. We have developed a proof-of-concept computer vision system for diagnosis of perilunate/lunate dislocations on lateral wrist radiographs. This novel deep learning algorithm has potential to improve clinical sensitivity to ultimately prevent delayed or missed diagnosis of these injuries.

  View details for DOI 10.1097/PRS.0000000000010928

  View details for PubMedID 37467052

• Impact of Adding Carpal Tunnel Release or Trigger Finger Release to Carpometacarpal Arthroplasty on Postoperative Complications". Plastic and reconstructive surgery Trinh, P., Luan, A., Tawfik, V. L., Sheckter, C., Rochlin, D., Fox, P., Curtin, C. 2023

  Abstract

  BACKGROUND: This study assessed whether adding trigger finger or carpal tunnel release at the time of thumb carpometacarpal (CMC) arthroplasty would increase postoperative opioid use, readmissions, complications, and development of CRPS.METHODS: Using the IBM MarketScan Research Databases from 2012 to 2016, we identified a two groups of CMC arthroplasty patients. The "CMC only" group only had a CMC arthroplasty on the day of operation. The "multiple procedures" group had a CMC arthroplasty and concurrent carpal tunnel and / or trigger finger release. Between the two groups, we compared persistent opioid use, 30-day readmissions, 30-day complications, and diagnosis of complex regional pain syndrome (CRPS).RESULTS: The CMC only group consisted of 18,010 patients. The multiple procedures group consisted of 4,064 patients. These patients received a CMC arthroplasty and a carpal tunnel release (74%), a trigger finger release (20%), or both (6%). CMC only patients had lower rates of persistent opioid use compared to patients who underwent multiple procedures (16% vs 18%). Readmission rates were also lower for CMC only patients (3% vs 4%). CMC only patients had decreased odds of persistent opioid use (OR=0.85; 95% CI, 0.75-0.97, p=0.013) and readmissions (OR=0.80; 95% CI, 0.67-0.96, p=0.016). The most common reason for readmission was pain (16%).CONCLUSIONS: Adding another procedure to a CMC arthroplasty slightly increases the odds of adverse outcomes such as persistent opioid use and readmission. Patients and providers should weigh the efficiency of doing these procedures concurrently against the risk of performing multiple procedures at once.CLINICAL QUESTION / LEVEL OF EVIDENCE: Risk, II.

  View details for DOI 10.1097/PRS.0000000000010144

  View details for PubMedID 36728633

• Economic Evaluation of a Global Reconstructive Surgery Visiting Educator Program. Annals of surgery open : perspectives of surgical history, education, and clinical approaches Luan, A., Meyers, N., Le Thua, T. H., Dang, H. T., Phu, Q. V., Auten, B., Chang, J. 2022; 3 (3): e181

  Abstract

  The objective of this study was to quantify the cost-effectiveness and economic value of a reconstructive surgery visiting educator trip program in a resource-constrained setting.Reconstructive surgical capacity remains inadequate in low- and middle-income countries, resulting in chronic disability and a significant economic toll. Education and training of the local surgical workforce to sustainably expand capacity have been increasingly encouraged, but economic analyses of these interventions are lacking.Data were analyzed from 12 visiting educator trips and independently-performed surgical procedures at 3 Vietnamese hospitals between 2014 and 2019. A cost-effectiveness analysis was performed using standardized methodology and thresholds to determine cost-effectiveness. Sensitivity analyses were performed with disability weights, discounting, and costs from different perspectives. Economic benefit was estimated using both the human capital method and the value of a statistical life method, and a benefit-cost ratio was computed.In the base case analysis, the visiting educator program was very cost-effective at $581 per disability-adjusted life year (DALY) averted. Economic benefit was between $21·6 million and $29·3 million, corresponding to a 12- to 16-fold return on investment. Furthermore, when considering only costs to the organization, the cost decreased to $61 per DALY averted, with a 113- to 153-fold return on investment for the organization.Visiting educator programs, which build local reconstructive surgical capacity in limited-resource environments, can be very cost-effective with significant economic benefit and return on investment. These findings may help guide organizations, donors, and policymakers in resource allocation in global surgery.

  View details for DOI 10.1097/AS9.0000000000000181

  View details for PubMedID 37601156

  View details for PubMedCentralID PMC10431359

• Expansion of Reconstructive Surgical Capacity in Vietnam: Experience from the ReSurge Global Training Program. Plastic and reconstructive surgery Luan, A., Hau, L. T., Thom, D. H., Viet, P. Q., Auten, B., Chang, J. 1800

  Abstract

  BACKGROUND: Building local surgical capacity in low-income and middle-income countries is critical to addressing the unmet global surgical need. Visiting educator programs can be utilized to train local surgeons, but the quantitative impact on surgical capacity has not yet been fully described. The authors' objective was to evaluate the effectiveness of training utilizing a visiting educator program on local reconstructive surgical capacity in Vietnam.METHODS: A reconstructive surgery visiting educator program was implemented in Vietnam. Topics of training were based on needs defined by local surgeons, including those specializing in hand surgery, microsurgery, and craniofacial surgery. A retrospective analysis of annual case numbers corresponding to covered topics between the years 2014 and 2019 at each hospital was conducted to determine reconstructive surgical volume and procedures per surgeon over time. Direct costs, indirect costs, and value of volunteer services for each trip were calculated.RESULTS: Over the course of 5 years, 12 visiting educator trips were conducted across three hospitals in Vietnam. Local surgeons subsequently independently performed a total of 2018 operations corresponding to topics covered during visiting educator trips, or a mean of 136 operations annually per surgeon. Within several years, the hospitals experienced an 81.5 percent increase in surgical volume for these reconstructive clinical conditions, and annual case volume continues to increase over time. Total costs were $191,290, for a mean cost per trip of $15,941.CONCLUSIONS: Surgical capacity can be successfully expanded by utilizing targeted visiting educator trips to train local reconstructive surgeons. Local providers ultimately independently perform an increased volume of complex procedures and provide further training to others.

  View details for DOI 10.1097/PRS.0000000000008874

  View details for PubMedID 35089267

• Are We Curing by Cutting? A Call for Long-Term Follow Up and Outcomes Research in Global Surgery Interventions - Perspective. International journal of surgery (London, England) Luan, A., Mghase, A. E., Meyers, N., Chang, J. 2021

  Abstract

  Success in global surgery interventions cannot be claimed until consistent long-term follow up is achieved and corresponding outcomes are studied. However, post-operative outcomes remain inconsistently collected and analyzed in the setting of global surgery, with current efforts largely focused on the delivery of surgical care. Barriers in low- and middle-income countries include patient cost and distance, low surgical workforce capacity, poor patient health literacy, lack of affordable technology availability, inconsistent documentation, and structural deficiencies. Here, we suggest that future work can be focused on (1) enhancing systems to facilitate long-term follow up and care, (2) expanding availability and adoption of electronic medical record systems, and (3) collaboration with local surgeons in the development of international cross-organizational registries and standardized quality measures. Long-term collaborations between local healthcare administrators and providers, policymakers, international bodies, nonprofit organizations, patients, and the private sector are necessary to build and sustain processes to achieve reliable long-term follow up and rigorous data collection, with the goal of ultimately ensuring better patient outcomes.

  View details for DOI 10.1016/j.ijsu.2021.01.011

  View details for PubMedID 33513453

• Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) for Lymphedema Prevention after Axillary Lymph Node Dissection-A Single Institution Experience and Feasibility of Technique. Journal of clinical medicine Lipman, K., Luan, A., Stone, K., Wapnir, I., Karin, M., Nguyen, D. 2021; 11 (1)

  Abstract

  While surgical options exist to treat lymphedema after axillary lymph node dissection (ALND), the lymphatic microsurgical preventive healing approach (LYMPHA) has been introduced as a preventive measure performed during the primary surgery, thus avoiding the morbidity associated with lymphedema. Here, we highlight details of our operative technique and review postoperative outcomes. For our patients, limb measurements and body composition analyses were performed pre- and postoperatively. Intraoperatively, axillary reverse lymphatic mapping was performed with indocyanine green (ICG) and lymphazurin. SPY-PHI imaging was used to visualize the ICG uptake into axillary lymphatics. Cut lymphatics from excised nodes were preserved for lymphaticovenous anastomosis (LVA). At the completion of the microanastomosis, ICG was visualized draining from the lymphatic through the recipient vein. A retrospective review identified nineteen patients who underwent complete or partial mastectomy with ALND and subsequent LYMPHA over 19 months. The number of LVAs performed per patient ranged between 1-4 per axilla. The operating time ranged from 32-95 min. There were no surgical complications, and thus far one patient developed mild lymphedema with an average follow up of 10 months. At the clinic follow up, ICG and SPY angiography were used to confirm intact lymphatic conduits with an uptake of ICG across the axilla. This study supports LYMPHA as a feasible and effective method for lymphedema prevention.

  View details for DOI 10.3390/jcm11010092

  View details for PubMedID 35011833

• Single-Unit technique for the use of acellular dermal matrix in immediate expander-based breast reconstruction. Journal of plastic, reconstructive & aesthetic surgery : JPRAS Luan, A., Patel, A. A., Martin, S. A., Nazerali, R. S. 2020

  Abstract

  BACKGROUND: The use of acellular dermal matrices (ADMs) in immediate two-stage prosthetic breast reconstruction following mastectomy is now a common practice. The procedure confers several compelling benefits, including coverage of the inferior pole, enhanced definition of the inframammary fold, and reduction of capsular contracture. However, operative techniques used to create the ADM inferolateral sling can be unwieldy in practice, typically involving the placement of the ADM followed by positioning and anchoring of the prosthetic expander. At best, this may be a relatively minor nuisance, but may potentially influence outcomes, including discrepancies in symmetry.METHODS: We present a novel modification that aims to streamline this procedure. Perforations are made through the allograft, through which the tissue expander tabs are brought through and sutured together ex vivo to allow the ADM and expander to be placed into the inframammary fold position as a single unit. A retrospective chart review was then performed of patients who underwent breast reconstruction utilizing this technique between July 2015 and December 2018. Outcomes including postsurgical complications such as infection, malposition, and reoperation were analyzed.RESULTS: Sixty-two patients met the inclusion criteria, corresponding to 108 breasts. The average follow-up was 18 months. The overall complication rate was 29.6% of breasts. The most commonly observed complications were mastectomy skin necrosis (9.3%) and major infection (8.3%). There was a 7.4% rate of malposition.CONCLUSIONS: This simple but effective modification in ADM technique is associated with a comparable complication rate and allows for greater ease and consistency in tissue expander placement.

  View details for DOI 10.1016/j.bjps.2020.10.048

  View details for PubMedID 33248935

• Assessing the Accuracy of a 3-Dimensional Surface Imaging System in Breast Volume Estimation. Annals of plastic surgery Kwong, J. W., Tijerina, J. D., Choi, S. n., Luan, A. n., Feng, C. L., Nguyen, D. H., Lee, G. K., Nazerali, R. S. 2020

  Abstract

  Preoperative prediction of breast volume can guide patient expectations and aid surgical planning in breast reconstruction. Here, we evaluate the accuracy of a portable surface imager (Crisalix S.A., Lausanne, Switzerland) in predicting breast volume compared with anthropomorphic estimates and intraoperative specimen weights.Twenty-five patients (41 breasts) undergoing mastectomy were scanned preoperatively with the Crisalix surface imager, and 1 of 3 attending plastic surgeons provided an anthropomorphic volume estimate. Intraoperative mastectomy weights were used as the gold standard. Volume conversions were performed assuming a density of 0.958 g/cm.The Pearson correlation coefficient between imager estimates and intraoperative volumes was 0.812. The corresponding value for anthropomorphic estimates and intraoperative volumes was 0.848. The mean difference between imager and intraoperative volumes was -233.5 cm, whereas the mean difference between anthropomorphic estimates and intraoperative volumes was -102.7 cm. Stratifying by breast volume, both surface imager and anthropomorphic estimates closely matched intraoperative volumes for breast volumes 600 cm and less, but the 2 techniques tended to underestimate true volumes for breasts larger than 600 cm. Stratification by plastic surgeon providing the estimate and breast surgeon performing the mastectomy did not eliminate this underestimation at larger breast volumes.For breast volumes 600 cm and less, the accuracy of the Crisalix surface imager closely matches anthropomorphic estimates given by experienced plastic surgeons and true volumes as measured from intraoperative specimen weights. Surface imaging may potentially be useful as an adjunct in surgical planning and guiding patient expectations for patients with smaller breast sizes.

  View details for DOI 10.1097/SAP.0000000000002244

  View details for PubMedID 32032116

• Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds. Advances in wound care Hu, M. S., Hong, W. X., Januszyk, M., Walmsley, G. G., Luan, A., Maan, Z. N., Moshrefi, S., Tevlin, R., Wan, D. C., Gurtner, G. C., Longaker, M. T., Lorenz, H. P. 2018; 7 (8): 262-275

  Abstract

  Objective: In early gestation, fetal wounds heal without fibrosis in a process resembling regeneration. Elucidating this remarkable mechanism can result in tremendous benefits to prevent scarring. Fetal mouse cutaneous wounds before embryonic day (E)18 heal without scar. Herein, we analyze expression profiles of fetal and postnatal wounds utilizing updated gene annotations and pathway analysis to further delineate between repair and regeneration. Approach: Dorsal wounds from time-dated pregnant BALB/c mouse fetuses and adult mice at various time points were collected. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was utilized to select genes with >2-fold expression differences with a false discovery rate of <2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways. Results: Our analysis identified 471 differentially expressed genes in fetal versus adult wounds following injury. Utilizing enrichment analysis of significant genes, we identified the top 20 signaling pathways that were upregulated and downregulated at 1 and 12 h after injury. At 24 h after injury, we discovered 18 signaling pathways upregulated in adult wounds and 11 pathways upregulated in fetal wounds. Innovation: These novel target genes and pathways may reveal repair mechanisms of the early fetus that promote regeneration over fibrosis. Conclusion: Our microarray analysis recognizes hundreds of possible genes as candidates for regulators of scarless versus scarring wound repair. Enrichment analysis reveals 109 signaling pathways related to fetal scarless wound healing.

  View details for DOI 10.1089/wound.2017.0779

  View details for PubMedID 30087802

  View details for PubMedCentralID PMC6080120

• Comparison of Outcomes of Total Esophageal Reconstruction With Supercharged Jejunal Flap, Colonic Interposition, and Gastric Pull-up ANNALS OF PLASTIC SURGERY Luan, A., Hunter, C. L., Crowe, C. S., Lee, G. K. 2018; 80: S274-S278

  Abstract

  Esophageal reconstruction following esophagectomy is a complex operation with significant morbidity. Gastric pull-up (GPU) has historically been the first-line operation followed by the colonic interposition (CI) graft, but recently, the use of a pedicled, supercharged jejunal flap (SJF) has reemerged as an alternative. However, comprehensive reports on outcomes of SJFs remain limited, with exceedingly few direct comparisons of outcomes.A retrospective chart review was completed for patients who underwent thoracic or total esophageal reconstruction between 2004 and 2014 at a single institution. A comparison of patient characteristics and outcomes was performed for 15 patients reconstructed with an SJF, 4 with CI, and 85 with GPU.Ten patients in the SJF group and 3 in the CI group underwent prior GPU with complications resulting in esophageal discontinuity. The CI group had significantly longer intensive care and overall hospital stays than either other group. Forty percent (SJF), 100% (CI), and 56% (GPU) experienced at least 1 complication during their postoperative hospitalization, most frequently bowel obstruction after SJF, anastomotic leak (CI), and pulmonary complications and arrhythmias (GPU). Rates of anastomotic leakage were 13% (GPU), 75% (CI), and 13% (SJF). Reoperation was required in 27% following SJF compared with 75% following CI and 19% following GPU. There was 1 CI graft failure and no SJF failures.The SJF is a reasonable first-line option for esophageal reconstruction, with comparable recovery, complication rate, and functional outcomes compared with the traditional GPU. When the stomach is unavailable, the SJF is superior to CI.

  View details for DOI 10.1097/SAP.0000000000001471

  View details for Web of Science ID 000473114300009

  View details for PubMedID 29634501

• Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds ADVANCES IN WOUND CARE Hu, M. S., Hong, W., Januszyk, M., Walmsley, G. G., Luan, A., Maan, Z. N., Moshrefi, S., Tevlin, R., Wan, D. C., Gurtner, G. C., Longaker, M. T., Lorenz, H. 2018

  View details for DOI 10.1089/wound.2017.0779

  View details for Web of Science ID 000429548900001

• Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts ADVANCES IN WOUND CARE Hu, M. S., Borrelli, M. R., Januszyk, M., Luan, A., Malhotra, S., Walmsley, G. G., Hong, W., Tevlin, R., Gurtner, G. C., Longaker, M. T., Lorenz, H. P. 2018; 7 (1): 1–10

  Abstract

  Objective: Fetuses early in gestation heal skin wounds without forming scars. The biological mechanisms behind this process are largely unknown. Fibroblasts, however, are cells known to be intimately involved in wound healing and scar formation. We examined fibroblasts in different stages of development to characterize differences in gene expression that may result in the switch from regenerative wound repair to repair with scarring. Approach: Fibroblasts were isolated and cultured from the back skin of BALB/c wild-type mouse fetuses at embryonic day (E)14 and E18 (n = 10). The fibroblast total RNA was extracted, and microarray analysis was conducted using chips containing 42,000 genes. Significance analysis of microarrays was performed to identify genes with greater than twofold expression difference and a false discovery rate of less than two. Identified genes subsequently underwent enrichment analysis to detect differentially expressed pathways. Results: Two hundred seventy-five genes were differentially expressed between E14 and E18 in fetal fibroblasts. Thirty genes were significantly downregulated and 245 genes were significantly upregulated at E18 compared with E14. Ingenuity pathway analysis identified the top 20 signaling pathways differentially activated in fetal fibroblasts between the E18 and E14 time points. Innovation: To our knowledge, this work represents the first instance where differentially expressed genes and signaling pathways between fetal fibroblasts at E14 and E18 have been studied. Conclusion: The genes and pathways identified here potentially underlie the mechanism behind the transition from fetal wound healing via regeneration to wound healing by repair, and may prove to be key targets for future therapeutics.

  View details for PubMedID 29344429

• Noncoding RNAs in Wound Healing: A New and Vast Frontier ADVANCES IN WOUND CARE Luan, A., Hu, M. S., Leavitt, T., Brett, E. A., Wang, K. C., Longaker, M. T., Wan, D. C. 2018; 7 (1): 19–27

  Abstract

  Significance: Wound healing requires a highly orchestrated coordination of processes that are not yet fully understood. Therefore, available clinical therapies are thus far limited in their efficacy in preventing and treating both chronic wounds and scars. Current gene-based therapeutics is largely based on our understanding of the protein-coding genome and proteins involved in known wound healing pathways. Recent Advances: Noncoding RNAs such as microRNAs and long noncoding RNAs have recently been found to be significant modulators of gene expression in diverse cellular pathways. Research has now implicated noncoding RNAs in nearly every stage of the wound healing process, suggesting that they may serve as clinical therapeutic targets. Noncoding RNAs are critical regulators in processes such as angiogenesis and cutaneous cell migration and proliferation, including classically described biological pathways previously attributed to mostly protein constituents. Critical Issues: The complexity and diversity of the interactions of noncoding RNAs with their targets and other binding partners require thorough characterization and understanding of their functions before they may be altered to modulate human wound healing pathways. Future Directions: Research in the area of noncoding RNAs continues to rapidly expand our understanding of their potential roles in physiological and pathological wound healing. Coupled with improving technologies to enhance or suppress target noncoding RNA in vivo, these advances hold great promise in the development of new therapies for wound healing.

  View details for PubMedID 29344431

  View details for PubMedCentralID PMC5770091

• Ultrasound-assisted liposuction provides a source for functional adipose-derived stromal cells CYTOTHERAPY Duscher, D., Maan, Z. N., Luan, A., Aitzetmueller, M. M., Brett, E. A., Atashroo, D., Whittam, A. J., Hu, M. S., Walmsley, G. G., Houschyar, K. S., Schilling, A. F., Machens, H., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2017; 19 (12): 1491–1500

  Abstract

  Regenerative medicine employs human mesenchymal stromal cells (MSCs) for their multi-lineage plasticity and their pro-regenerative cytokine secretome. Adipose-derived mesenchymal stromal cells (ASCs) are concentrated in fat tissue, and the ease of harvest via liposuction makes them a particularly interesting cell source. However, there are various liposuction methods, and few have been assessed regarding their impact on ASC functionality. Here we study the impact of the two most popular ultrasound-assisted liposuction (UAL) devices currently in clinical use, VASER (Solta Medical) and Lysonix 3000 (Mentor) on ASCs.After lipoaspirate harvest and processing, we sorted for ASCs using fluorescent-assisted cell sorting based on an established surface marker profile (CD34+CD31-CD45-). ASC yield, viability, osteogenic and adipogenic differentiation capacity and in vivo regenerative performance were assessed.Both UAL samples demonstrated equivalent ASC yield and viability. VASER UAL ASCs showed higher osteogenic and adipogenic marker expression, but a comparable differentiation capacity was observed. Soft tissue healing and neovascularization were significantly enhanced via both UAL-derived ASCs in vivo, and there was no significant difference between the cell therapy groups.Taken together, our data suggest that UAL allows safe and efficient harvesting of the mesenchymal stromal cellular fraction of adipose tissue and that cells harvested via this approach are suitable for cell therapy and tissue engineering applications.

  View details for PubMedID 28917626

  View details for PubMedCentralID PMC5723208

• Delayed prosthetic breast reconstruction without the use of acellular dermal matrix EUROPEAN JOURNAL OF PLASTIC SURGERY Mittermiller, P. A., Nazerali, R. S., Glaus, S. W., Perez, M. G., Luan, A., Kahn, D. M., Lee, G. K. 2017; 40 (6): 533–40

  View details for DOI 10.1007/s00238-017-1300-4

  View details for Web of Science ID 000416142400007

• Dynamic Rheology for the Prediction of Surgical Outcomes in Autologous Fat Grafting. Plastic and reconstructive surgery Luan, A., Zielins, E. R., Wearda, T., Atashroo, D. A., Blackshear, C. P., Raphel, J., Brett, E. A., Flacco, J., Alyono, M. C., Momeni, A., Heilshorn, S., Longaker, M. T., Wan, D. C. 2017

  Abstract

  Due to the abundance and biocompatibility of fat, lipotransfer has become an attractive method for treating soft tissue deficits. However, it is limited by unpredictable graft survival and retention. Currently, little is known about the viscoelastic properties of fat after various injection methods. Here, we assess the effects of cannula diameter, length, and shape on the viscoelastic properties, structure, and retention of fat.Human lipoaspirate was harvested using suction-assisted liposuction and prepared for grafting. A syringe pump was used to inject fat at a controlled flow rate through cannulas of varying gauge, length, and shape. Processed samples were tested in triplicate on an oscillatory rheometer to measure their viscoelastic properties. Fat grafts from each group were placed into the scalps of immunocompromised mice. After 8 weeks, graft retention was measured using micro-CT and grafts were explanted for histological analysis.Lipoaspirate injected through narrower, longer, and bent cannulas exhibited more shear thinning with diminished quality. The storage modulus (G') of fat processed with 18-gauge cannulas was significantly lower than when processed with 14-gauge or larger cannulas, which also corresponded with inferior in vivo histological structure. Similarly, the longer cannula group had a significantly lower G' than the shorter cannula, and was associated with decreased graft retention.Discrete modifications in the methods used for fat placement can have a significant impact on immediate graft integrity, and ultimately on graft survival and quality. Respecting these biomechanical influences during the placement phase of lipotransfer may allow surgeons to optimize outcomes.

  View details for DOI 10.1097/PRS.0000000000003578

  View details for PubMedID 28574947

• Validation of a Cognitive Task Simulation and Rehearsal Tool for Open Carpal Tunnel Release. Archives of plastic surgery Paro, J. A., Luan, A., Lee, G. K. 2017; 44 (3): 223-227

  Abstract

  Carpal tunnel release is one of the most common surgical procedures performed by hand surgeons. The authors created a surgical simulation of open carpal tunnel release utilizing a mobile and rehearsal platform app. This study was performed in order to validate the simulator as an effective training platform for carpal tunnel release.The simulator was evaluated using a number of metrics: construct validity (the ability to identify variability in skill levels), face validity (the perceived ability of the simulator to teach the intended material), content validity (that the simulator was an accurate representation of the intended operation), and acceptability validity (willingness of the desired user group to adopt this method of training). Novices and experts were recruited. Each group was tested, and all participants were assigned an objective score, which served as construct validation. A Likert-scale questionnaire was administered to gauge face, content, and acceptability validity.Twenty novices and 10 experts were recruited for this study. The objective performance scores from the expert group were significantly higher than those of the novice group, with surgeons scoring a median of 74% and medical students scoring a median of 45%. The questionnaire responses indicated face, content, and acceptability validation.This mobile-based surgical simulation platform provides step-by-step instruction for a variety of surgical procedures. The findings of this study help to demonstrate its utility as a learning tool, as we confirmed construct, face, content, and acceptability validity for carpal tunnel release. This easy-to-use educational tool may help bring surgical education to a new-and highly mobile-level.

  View details for DOI 10.5999/aps.2017.44.3.223

  View details for PubMedID 28573097

• Transversus Abdominis Plane Block and Free Flap Abdominal Tissue Breast Reconstruction: Is There a True Reduction in Postoperative Narcotic Use? Annals of plastic surgery Hunter, C., Shakir, A., Momeni, A., Luan, A., Steffel, L., Horn, J., Nguyen, D., Lee, G. K. 2017; 78 (3): 254-259

  Abstract

  The use of the transversus abdominis plane (TAP) block is increasing in abdominally based autologous tissue breast reconstruction as a method to provide postoperative donor site analgesia. The purpose of this study was to evaluate the efficacy of the TAP block in the immediate postoperative period.A retrospective analysis of all patients who underwent autologous microsurgical breast reconstruction over a 2-year period (2013-2015) was conducted. Only patients with an abdominal donor site were included. Patients were grouped based on the presence or absence of TAP blocks. Primary endpoints included patient-reported pain score, daily and total narcotic use during the hospitalization, antiemetic use, as well as complications.We identified 40 patients that had undergone abdominal-based free flap breast reconstruction and TAP block catheter placement for postoperative analgesia that met inclusion criteria. This group was then compared with a matched cohort of 40 patients without TAP blocks. There were no complications associated with using the TAP catheters. There was no statistically significant difference in postoperative pain scores, daily or total narcotic use during the hospitalization, or antiemetic use between the 2 groups. Although not statistically significant, linear regression analysis identified trends of improved donor site analgesia in select groups, such as unilateral immediate reconstructions, body mass index greater than 30 kg/m, and those without abdominal mesh placed at the time of donor site closure in the TAP block group.Constant delivery of local anesthetic through the TAP block appears to be safe; however, it did not reduce narcotic requirements or postoperative pain scores in patients undergoing abdominal-based free flap breast reconstruction.

  View details for DOI 10.1097/SAP.0000000000000873

  View details for PubMedID 28118232

• Transversus Abdominis Plane Block and Free Flap Abdominal Tissue Breast Reconstruction Is There a True Reduction in Postoperative Narcotic Use? ANNALS OF PLASTIC SURGERY Hunter, C., Shakir, A., Momeni, A., Luan, A., Steffel, L., Horn, J., Dung Nguyen, D., Lee, G. K. 2017; 78 (3): 254-259

  Abstract

  The use of the transversus abdominis plane (TAP) block is increasing in abdominally based autologous tissue breast reconstruction as a method to provide postoperative donor site analgesia. The purpose of this study was to evaluate the efficacy of the TAP block in the immediate postoperative period.A retrospective analysis of all patients who underwent autologous microsurgical breast reconstruction over a 2-year period (2013-2015) was conducted. Only patients with an abdominal donor site were included. Patients were grouped based on the presence or absence of TAP blocks. Primary endpoints included patient-reported pain score, daily and total narcotic use during the hospitalization, antiemetic use, as well as complications.We identified 40 patients that had undergone abdominal-based free flap breast reconstruction and TAP block catheter placement for postoperative analgesia that met inclusion criteria. This group was then compared with a matched cohort of 40 patients without TAP blocks. There were no complications associated with using the TAP catheters. There was no statistically significant difference in postoperative pain scores, daily or total narcotic use during the hospitalization, or antiemetic use between the 2 groups. Although not statistically significant, linear regression analysis identified trends of improved donor site analgesia in select groups, such as unilateral immediate reconstructions, body mass index greater than 30 kg/m, and those without abdominal mesh placed at the time of donor site closure in the TAP block group.Constant delivery of local anesthetic through the TAP block appears to be safe; however, it did not reduce narcotic requirements or postoperative pain scores in patients undergoing abdominal-based free flap breast reconstruction.

  View details for DOI 10.1097/SAP.0000000000000873

  View details for Web of Science ID 000394386700004

• Hospital Transfer of Open Tibial Fractures Requiring Microsurgical Reconstruction Negatively Impacts Clinical Outcomes. Annals of plastic surgery Crowe, C. S., Luan, A., Lee, G. K. 2017

  Abstract

  Open tibial fractures are orthopedic emergencies that may present with severe soft tissue damage. Free tissue transfer is often required when local tissues are insufficient and patients may require hospital transfer to tertiary care centers for this purpose. Although the negative impact of inter-facility transfer has been well demonstrated in trauma patients, less is known regarding transfers for lower extremity injury patients. This study investigates differences in outcomes based on transfer status after open tibial fracture.Thirty-four consecutive open tibial fractures requiring free tissue transfer over a 13-year period (2001-2014) were retrospectively reviewed. Patients transferred from outside facilities were compared to non-transferred patients in regards to demographics, injury, surgical characteristics, and outcomes (mean follow-up of 2.5 years). Student t tests and chi square analysis were used to compare means and proportions, respectively.One-half of patients were transferred from an outside hospital. Transferred and nontransferred patients were not significantly different in regard to age, sex, comorbidities, mechanism of injury, and Gustilo grade. There was no significant difference in the method of bony fixation or free flap used for soft tissue coverage. The time to wound vacuum-assisted closure placement was longer in transferred patients, though this difference was not found to be significant (2.4 vs 3.3 days, P = 0.55). Time to definitive bony fixation was delayed in the transfer group by 9 days (5.2 vs 14.1 days, P = 0.05) and to tissue coverage by 7 days (14.2 vs 20.9 days, P = 0.13). Rates of flap loss and amputation did not differ between the groups. However, transferred patients were more likely to develop osteomyelitis (risk ratio [RR], 3.0; P = 0.03), nonunion (RR, 5.0; P = 0.09), and require hardware removal (RR, 3.3; P = 0.01).Transferred and nontransferred patients were not significantly different in their demographics or presentation. However, an analysis of clinical outcomes showed that transfer was associated with increased rates of osteomyelitis, nonunion, and hardware removal. Although likely multifactorial, this study suggests that a delay to definitive fixation and soft tissue coverage contributes to the increased rate of complications and poorer prognosis.

  View details for DOI 10.1097/SAP.0000000000000972

  View details for PubMedID 28118229

• Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration. Stem cells translational medicine Brett, E., Zielins, E. R., Luan, A., Ooi, C. C., Shailendra, S., Atashroo, D., Menon, S., Blackshear, C., Flacco, J., Quarto, N., Wang, S. X., Longaker, M. T., Wan, D. C. 2017; 6 (1): 151-160

  Abstract

  Clinical translation of cell-based strategies for tissue regeneration remains challenging because survival of implanted cells within hostile, hypoxic wound environments is uncertain. Overexpression of B-cell lymphoma 2 (Bcl-2) has been shown to inhibit apoptosis in implanted cells. The present study describes an "off the shelf" prefabricated scaffold integrated with magnetic nanoparticles (MNPs) used to upregulate Bcl-2 expression in implanted adipose-derived stromal cells for bone regeneration. Iron oxide cores were sequentially coated with branched polyethyleneimine, minicircle plasmid encoding green fluorescent protein and Bcl-2, and poly-β-amino ester. Through in vitro assays, increased osteogenic potential and biological resilience were demonstrated in the magnetofected group over control and nucleofected groups. Similarly, our in vivo calvarial defect study showed that magnetofection had an efficiency rate of 30%, which in turn resulted in significantly more healing compared with control group and nucleofected group. Our novel, prefabricated MNP-integrated scaffold allows for in situ postimplant temporospatial control of cell transfection to augment bone regeneration. Stem Cells Translational Medicine 2017;6:151-160.

  View details for DOI 10.5966/sctm.2016-0051

  View details for PubMedID 28170185

• Cleft Lip Standardized Patient Examinations: The Role in Plastic Surgery Resident Education CLEFT PALATE-CRANIOFACIAL JOURNAL Wright, E. J., Khosla, R. K., Howell, L., Luan, A., Lee, G. K. 2016; 53 (6): 634-639

  Abstract

    Our institution has incorporated the use of objective structured clinical examinations (OSCE) in our residency curriculum. The OSCE provides trainee education and evaluation while addressing the six Accreditation Council for Graduate Medical Education (ACGME) core competencies required within training programs. We report our program's experience with the first cleft OSCE ever conducted.  A validated method for administration of OSCEs currently used at our medical school was utilized for residents in postgraduate years (PGYs) 3 through 6. The video-recorded patient encounter involved a 1-month-old newborn with a unilateral cleft lip and palate and used standardized patient actors as parents. A post-encounter written exam assessed medical knowledge. A questionnaire regarding the utility of the exercise was administered to residents after the OSCE. Results were evaluated using analysis of variance (P < .05).  There was a positive correlation with increasing level of training in terms of medical knowledge (P < .04). Residents in PGY-3 and PGY-4 demonstrated lower understanding of the surgical markings and details of the lip repair compared with those in PGY-5 and PGY-6 (P < .03). All residents performed similarly on evaluation of the remaining ACGME core competencies. All residents agreed that this was a realistic and useful encounter.  Results of our cleft OSCE demonstrate that medical knowledge regarding the evaluation, management, and surgical repair of patients is less in midlevel residents. All residents expressed an interest in earlier exposure to pediatric patients in the training period. Although a cleft OSCE does not replace clinical rotations, it is a valuable adjunct to training and evaluation of trainees, particularly for junior residents.

  View details for DOI 10.1597/15-121

  View details for Web of Science ID 000388005700004

  View details for PubMedID 26720521

• Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration. Stem cells translational medicine Brett, E., Zielins, E. R., Luan, A., Ooi, C. C., Shailendra, S., Atashroo, D., Menon, S., Blackshear, C., Flacco, J., Quarto, N., Wang, S. X., Longaker, M. T., Wan, D. C. 2016

  Abstract

  : Clinical translation of cell-based strategies for tissue regeneration remains challenging because survival of implanted cells within hostile, hypoxic wound environments is uncertain. Overexpression of B-cell lymphoma 2 (Bcl-2) has been shown to inhibit apoptosis in implanted cells. The present study describes an "off the shelf" prefabricated scaffold integrated with magnetic nanoparticles (MNPs) used to upregulate Bcl-2 expression in implanted adipose-derived stromal cells for bone regeneration. Iron oxide cores were sequentially coated with branched polyethyleneimine, minicircle plasmid encoding green fluorescent protein and Bcl-2, and poly-β-amino ester. Through in vitro assays, increased osteogenic potential and biological resilience were demonstrated in the magnetofected group over control and nucleofected groups. Similarly, our in vivo calvarial defect study showed that magnetofection had an efficiency rate of 30%, which in turn resulted in significantly more healing compared with control group and nucleofected group. Our novel, prefabricated MNP-integrated scaffold allows for in situ postimplant temporospatial control of cell transfection to augment bone regeneration.The use of adipose-derived stem cells as transplanted cells in wounded areas is desirable for their regenerative potential, but they are difficult to use owing to their fragility. Enhancing their survival in the context of a calvarial defect can be achieved by stimulating antiapoptotic protein expression in the cells themselves, through a plasmid expression vector. The present study used a nonintegrating minicircle plasmid encoding B-cell lymphoma 2 attached to a magnetic nanoparticle to facilitate in vivo transfection with temporospatial control (external magnetic field). This in situ system stimulates cell survival through gene expression and knock-on bone regeneration through cell survival.

  View details for PubMedID 27484867

• Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells JOURNAL OF TRANSLATIONAL MEDICINE Duscher, D., Luan, A., Rennert, R. C., Atashroo, D., Maan, Z. N., Brett, E. A., Whittam, A. J., Ho, N., Lin, M., Hu, M. S., Walmsley, G. G., Wenny, R., Schmidt, M., Schilling, A. F., Machens, H., Huemer, G. M., Wan, D. C., Longaker, M. T., Gurtner, G. C. 2016; 14

  Abstract

  Adipose-derived stem cells (ASCs) have been identified as a population of multipotent cells with promising applications in tissue engineering and regenerative medicine. ASCs are abundant in fat tissue, which can be safely harvested through the minimally invasive procedure of liposuction. However, there exist a variety of different harvesting methods, with unclear impact on ASC regenerative potential. The aim of this study was thus to compare the functionality of ASCs derived from the common technique of suction-assisted lipoaspiration (SAL) versus resection.Human adipose tissue was obtained from paired abdominoplasty and SAL samples from three female donors, and was processed to isolate the stromal vascular fraction. Fluorescence-activated cell sorting was used to determine ASC yield, and cell viability was assayed. Adipogenic and osteogenic differentiation capacity were assessed in vitro using phenotypic staining and quantification of gene expression. Finally, ASCs were applied in an in vivo model of tissue repair to evaluate their regenerative potential.SAL specimens provided significantly fewer ASCs when compared to excised fat tissue, however, with equivalent viability. SAL-derived ASCs demonstrated greater expression of the adipogenic markers FABP-4 and LPL, although this did not result in a difference in adipogenic differentiation. There were no differences detected in osteogenic differentiation capacity as measured by alkaline phosphatase, mineralization or osteogenic gene expression. Both SAL- and resection-derived ASCs enhanced significantly cutaneous healing and vascularization in vivo, with no significant difference between the two groups.SAL provides viable ASCs with full capacity for multi-lineage differentiation and tissue regeneration, and is an effective method of obtaining ASCs for cell-based therapies.

  View details for DOI 10.1186/s12967-016-0881-1

  View details for Web of Science ID 000375475200004

  View details for PubMedID 27153799

  View details for PubMedCentralID PMC4859988

• Effects of A Novel Decision Aid for Breast Reconstruction: A Randomized Prospective Trial. Annals of plastic surgery Luan, A., Hui, K. J., Remington, A. C., Liu, X., Lee, G. K. 2016; 76: S249-54

  Abstract

  The choice to undergo mastectomy and breast reconstruction is a highly personal decision with profound psychosocial effects, and ultimately, the decision between implant- and autologous tissue-based reconstruction should be made based on a combination of factual information and the patient's personal values and preferences. Unfortunately, patients undergoing breast reconstruction surgery may experience decision regret. Decision aids promote patient involvement in decision making by not only providing standard information about options, but also emphasizing comparative risks, benefits, and alternatives, and most importantly by providing clarification exercises regarding personal values to guide patients toward an individualized decision.We developed a novel decision aid to provide decision support and structured guidance for prosthetic, autologous, and combined prosthetic-autologous breast reconstruction surgery. New breast reconstruction patients of one surgeon at our institution were randomized by week to either receive the decision aid or standard preconsultation material. Immediately preceding their new patient consultation clinic visit, patients were asked to complete the validated Decisional Conflict Scale and the BREAST-Q Preoperative survey. After 3 to 5 months following breast mound reconstruction, patients were asked to complete the Decision Regret Scale, BREAST-Q Postoperative survey, and the Hospital Anxiety and Depression Scale.Patients who received the decision aid demonstrated a trend toward decreased preoperative decisional conflict (mean of 13.3 ± 5.5, compared to 26.2 ± 4.2; n = 8 per group, P = 0.069), with similar preoperative BREAST-Q scores. Most patients desired to know "everything" regarding their reconstruction surgery (75%), and to be "very involved" in the decisions in their care (81%), with remaining patients wanting to know "as much as I need to be prepared" and to be "somewhat involved." Postoperatively, patients who received the decision aid demonstrated significantly less decision regret (P < 0.001), although there was no significant difference in anxiety, depression, or quality of life-related outcomes as measured by the BREAST-Q.The use of decision aids in breast reconstruction surgery may help decrease decisional conflict and regret through promoting improved information sharing and shared decision making, which are highly important in this particular setting, patient population, and in our move toward greater patient-centered care.

  View details for DOI 10.1097/SAP.0000000000000722

  View details for PubMedID 27070681

• Superior Gluteal Artery Perforator Flap: The Beauty of the Buttock. Annals of plastic surgery Hunter, C., Moody, L., Luan, A., Nazerali, R., Lee, G. K. 2016; 76: S191-5

  Abstract

  The superior gluteal artery perforator (SGAP) flap is a useful technique for breast reconstruction. This perforator flap allows for the transfer of the patient's own skin and subcutaneous tissue with minimal donor-site morbidity. Despite its usefulness, the SGAP flap is not widely used among reconstructive surgeons. The challenging perforator dissection and need for microsurgery may contribute to the reluctant use of the flap by many reconstructive surgeons. The ability to perform a single-stage breast reconstruction with buttock tissue when abdominal or thigh tissue are unavailable provides a significant service to the patient desiring an autologous breast reconstruction.The authors performed a retrospective review and outcomes analysis of a single surgeon's surgical technique and experience. Consecutive patients, who underwent SGAP flaps for breast reconstruction during a 7-year period from 2007 to 2014, were compared to a matched cohort of consecutive patients undergoing deep inferior epigastric perforator (DIEP) flaps and clinical outcomes were analyzed.Thirteen patients underwent SGAP flap breast reconstruction for a total of 16 flaps during the study period compared to 34 consecutive DIEP flaps for breast reconstruction. There was no significant difference in flap or donor-site complications between the 2 groups. There was no statistically significant difference between the average operative time for unilateral breast reconstruction in the SGAP and DIEP flap groups. In 4 patients, a bipedicled SGAP flap was used due to perforator anatomy. All SGAP patients returned to full activity. Average follow-up time was 1 year.Although utilization of buttock tissue for breast reconstruction can be challenging and requires microsurgical expertise, in the hands of experienced microsurgeons the SGAP flap is a safe and reliable option for autologous breast reconstruction with minimal donor-site morbidity and excellent aesthetic results.

  View details for DOI 10.1097/SAP.0000000000000723

  View details for PubMedID 26808742

• Cell-Assisted Lipotransfer Improves Volume Retention in Irradiated Recipient Sites and Rescues Radiation-Induced Skin Changes STEM CELLS Luan, A., Duscher, D., Whittam, A. J., Paik, K. J., Zielins, E. R., Brett, E. A., Atashroo, D. A., Hu, M. S., Lee, G. K., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2016; 34 (3): 668-673

  Abstract

  Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy. Stem Cells 2016;34:668-673.

  View details for DOI 10.1002/stem.2256

  View details for Web of Science ID 000372552600013

• Cell-Assisted Lipotransfer Improves Volume Retention in Irradiated Recipient Sites and Rescues Radiation-Induced Skin Changes. Stem cells Luan, A., Duscher, D., Whittam, A. J., Paik, K. J., Zielins, E. R., Brett, E. A., Atashroo, D. A., Hu, M. S., Lee, G. K., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2016; 34 (3): 668-673

  Abstract

  Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy. Stem Cells 2016;34:668-673.

  View details for DOI 10.1002/stem.2256

  View details for PubMedID 26661694

• Enrichment of Adipose-Derived Stromal Cells for BMPR1A Facilitates Enhanced Adipogenesis TISSUE ENGINEERING PART A Zielins, E. R., Paik, K., Ransom, R. C., Brett, E. A., Blackshear, C. P., Luan, A., Walmsley, G. G., Atashroo, D. A., Senarath-Yapa, K., Momeni, A., Rennert, R., Sorkin, M., Seo, E. Y., Chan, C. K., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2016; 22 (3-4): 214-221

  Abstract

  Reconstruction of soft tissue defects has traditionally relied on the use of grafts and flaps, which may be associated with variable resorption and/or significant donor site morbidity. Cell-based strategies employing adipose-derived stromal cells (ASCs), found within the stromal vascular fraction (SVF) of adipose tissue, may offer an alternative strategy for soft tissue reconstruction. In this study, we investigated the potential of a bone morphogenetic protein receptor type 1A (BMPR1A)(+) subpopulation of ASCs to enhance de novo adipogenesis.Human lipoaspirate was enzymatically digested to isolate SVF and magnetic-activated cell separation was utilized to obtain BMPR1A(+) and BMPR1A(-) cells. These cells, along with unenriched cells, were expanded in culture and evaluated for adipogenic gene expression and in vitro adipocyte formation. Cells from each group were also labeled with a green fluorescent protein (GFP) lentivirus and transplanted into the inguinal fat pads, an adipogenic niche, of immunocompromised mice to determine their potential for de novo adipogenesis. Confocal microscopy along with staining of lipid droplets and vasculature was performed to evaluate the formation of mature adipocytes by transplanted cells.In comparison to BMPR1A(-) and unenriched ASCs, BMPR1A(+) cells demonstrated significantly enhanced adipogenesis when cultured in an adipogenic differentiation medium, as evidenced by increased staining with Oil Red O and increased expression of peroxisome proliferator-activating receptor gamma (PPAR-γ) and fatty acid-binding protein 4 (FABP4). BMPR1A(+) cells also formed significantly more adipocytes in vivo, as demonstrated by quantification of GFP+ adipocytes. Minimal formation of mature adipocytes was appreciated by BMPR1A(-) cells.BMPR1A(+) ASCs show an enhanced ability for adipogenesis in vitro, as shown by gene expression and histological staining. Furthermore, within an adipogenic niche, BMPR1A(+) cells possessed an increased capacity to generate de novo fat compared to BMPR1A(-) and unenriched cells. This suggests utility for the BMPR1A(+) subpopulation in cell-based strategies for soft tissue reconstruction.

  View details for DOI 10.1089/ten.tea.2015.0278

  View details for PubMedID 26585335

• Ultrasound-Assisted Liposuction Does Not Compromise the Regenerative Potential of Adipose-Derived Stem Cells. Stem cells translational medicine Duscher, D., Atashroo, D., Maan, Z. N., Luan, A., Brett, E. A., Barrera, J., Khong, S. M., Zielins, E. R., Whittam, A. J., Hu, M. S., Walmsley, G. G., Pollhammer, M. S., Schmidt, M., Schilling, A. F., Machens, H., Huemer, G. M., Wan, D. C., Longaker, M. T., Gurtner, G. C. 2016; 5 (2): 248-257

  Abstract

  Human mesenchymal stem cells (MSCs) have recently become a focus of regenerative medicine, both for their multilineage differentiation capacity and their excretion of proregenerative cytokines. Adipose-derived mesenchymal stem cells (ASCs) are of particular interest because of their abundance in fat tissue and the ease of harvest via liposuction. However, little is known about the impact of different liposuction methods on the functionality of ASCs. Here we evaluate the regenerative abilities of ASCs harvested via a third-generation ultrasound-assisted liposuction (UAL) device versus ASCs obtained via standard suction-assisted lipoaspiration (SAL). Lipoaspirates were sorted using fluorescent assisted cell sorting based on an established surface-marker profile (CD34+/CD31-/CD45-), to obtain viable ASCs. Yield and viability were compared and the differentiation capacities of the ASCs were assessed. Finally, the regenerative potential of ASCs was examined using an in vivo model of tissue regeneration. UAL- and SAL-derived samples demonstrated equivalent ASC yield and viability, and UAL ASCs were not impaired in their osteogenic, adipogenic, or chondrogenic differentiation capacity. Equally, quantitative real-time polymerase chain reaction showed comparable expression of most osteogenic, adipogenic, and key regenerative genes between both ASC groups. Cutaneous regeneration and neovascularization were significantly enhanced in mice treated with ASCs obtained by either UAL or SAL compared with controls, but there were no significant differences in healing between cell-therapy groups. We conclude that UAL is a successful method of obtaining fully functional ASCs for regenerative medicine purposes. Cells harvested with this alternative approach to liposuction are suitable for cell therapy and tissue engineering applications. Significance: Adipose-derived mesenchymal stem cells (ASCs) are an appealing source of therapeutic progenitor cells because of their multipotency, diverse cytokine profile, and ease of harvest via liposuction. Alternative approaches to classical suction-assisted liposuction are gaining popularity; however, little evidence exists regarding the impact of different liposuction methods on the regenerative functionality of ASCs. Human ASC characteristics and regenerative capacity were assessed when harvested via ultrasound-assisted (UAL) versus standard suction-assisted liposuction. ASCs obtained via UAL were of equal quality when directly compared with the current gold standard harvest method. UAL is an adjunctive source of fully functional mesenchymal stem cells for applications in basic research and clinical therapy.

  View details for DOI 10.5966/sctm.2015-0064

  View details for PubMedID 26702129

  View details for PubMedCentralID PMC4729547

• Flow-through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature. Microsurgery Luan, A., Galvez, M. G., Lee, G. K. 2016; 36 (1): 70-76

  Abstract

  Despite the options currently available for chest wall reconstruction, patients with complex composite defects may still pose a significant challenge for the reconstructive surgeon when only using conventional methods. In particular, prior radiotherapy and/or large en bloc resection may leave inadequate regional flaps and recipient vessels for free tissue transfer. Here, we describe a case in which we reconstruct a 14 cm × 18 cm complex chest wall defect, secondary to tumor resection and infected sternum debridement, with a pedicled flow-through omental flap to a 14 cm × 22 cm free anterolateral thigh flap using the omental gastroepiploic vessels as recipient vessels. Reconstruction was successful with excellent flap viability, and no complications at recipient or donor sites. We review the literature on complex chest wall reconstruction and introduce this valuable option of utilizing a pedicled omental flap as a flow-through flap to a free flap for patients without viable recipient vessels or local flaps.

  View details for DOI 10.1002/micr.22444

  View details for PubMedID 26140609

• RNA Sequencing for Identification of Differentially Expressed Noncoding Transcripts during Adipogenic Differentiation of Adipose-Derived Stromal Cells. Plastic and reconstructive surgery Luan, A., Paik, K. J., Li, J., Zielins, E. R., Atashroo, D. A., Spencley, A., Momeni, A., Longaker, M. T., Wang, K. C., Wan, D. C. 2015; 136 (4): 752-763

  Abstract

  Adipose-derived stromal cells represent a relatively abundant source of multipotent cells, with many potential applications in regenerative medicine. The present study sought to demonstrate the use of RNA sequencing in identifying differentially expressed transcripts, particularly long noncoding RNAs, associated with adipogenic differentiation to gain a clearer picture of the mechanisms responsible for directing adipose-derived stromal cell fate toward the adipogenic lineage.Human adipose-derived stromal cells were cultured in adipogenic differentiation media, and RNA was harvested at days 0, 1, 3, 5, and 7. Directional RNA sequencing libraries were prepared and sequenced. Paired-end reads were mapped to the human genome reference sequence hg19. Transcriptome assembly was performed and significantly differentially expressed transcripts were identified. Gene ontology term analysis was then performed to identify coding and noncoding transcripts of interest. Differential expression was verified by quantitative real-time polymerase chain reaction.Of 2868 significantly differentially expressed transcripts identified, 207 were noncoding. Enriched gene ontology terms among up-regulated coding transcripts notably reflected differentiation toward the adipogenic lineage. Enriched gene ontology terms among down-regulated coding transcripts reflected growth arrest. Guilt-by-association analysis revealed noncoding RNA candidates with potential roles in the process of adipogenic differentiation.The precise mechanisms that guide lineage-specific differentiation in multipotent cells are not yet fully understood. Defining long noncoding RNAs associated with adipogenic differentiation allows for potential manipulation of regulatory pathways in novel ways. The authors present RNA sequencing as a powerful tool for expanding the understanding of adipose-derived stromal cells and developing novel applications within regenerative medicine.

  View details for DOI 10.1097/PRS.0000000000001582

  View details for PubMedID 26090763

• Microfluidic single cell transcriptional analysis reveals subpopulations of adipose derived stromal cells with enhanced angiogenic potential Zielins, E. R., Januszyk, M., Luan, A., Brett, E. A., Paik, K., Walmsley, G. G., Gurtner, G. C., Longaker, M. T., Wan, D. C. ELSEVIER SCIENCE INC. 2015: E26

  View details for DOI 10.1016/j.jamcollsurg.2015.08.366

  View details for Web of Science ID 000386899000059

• What Makes a Plastic Surgery Residency Program Attractive? An Applicant's Perspective PLASTIC AND RECONSTRUCTIVE SURGERY Atashroo, D. A., Luan, A., Vyas, K. S., Zielins, E. R., Maan, Z., Duscher, D., Walmsley, G. G., Lynch, M. P., Davenport, D. L., Wan, D. C., Longaker, M. T., Vasconez, H. C. 2015; 136 (1): 189-196

  Abstract

  Plastic surgery is among the most competitive specialties in medicine, but little is known about the attributes of programs that are most attractive to successful applicants. This study aimed to understand and provide insights regarding program characteristics that are most influential to students when ranking plastic surgery programs.An anonymous online survey was conducted with newly matched plastic surgery residents for the integrated and combined Match in 2012 and 2013. Subjects were queried regarding their demographics, qualifications, application experiences, and motivations for residency program selection.A total of 92 of 245 matched plastic surgery residents (38 percent) responded to the survey. The perception of resident happiness was the most positive factor influencing program ranking, followed by high operative volume, faculty mentorship, and strong research infrastructure. Perception of a program as "malignant" was the most negative attribute. Applicants with Step 1 scores greater than 245 received significantly more interviews (p =0.001) and considered resident benefits less important (p < 0.05), but geographic location more important (p =0.005). Applicants who published more than two articles also received more interviews (p =0.001) and ranked a strong research infrastructure and program reputation as significantly more important (p < 0.05). Forty-two percent of applicants completed an away rotation at the program with which they matched, and these applicants were more likely to match at their number one ranked program (p = 0.001).Plastic surgery applicants have differing preferences regarding the ideal training program, but some attributes resonate. These trends can guide programs for improvement in attracting the best applicants.

  View details for DOI 10.1097/PRS.0000000000001365

  View details for Web of Science ID 000357097900001

  View details for PubMedID 26111321

• Studies in Fat Grafting: Part V. Cell-Assisted Lipotransfer to Enhance Fat Graft Retention Is Dose Dependent PLASTIC AND RECONSTRUCTIVE SURGERY Paik, K. J., Zielins, E. R., Atashroo, D. A., Maan, Z. N., Duscher, D., Luan, A., Walmsley, G. G., Momeni, A., Vistnes, S., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2015; 136 (1): 67-75

  Abstract

  Cell-assisted lipotransfer has shown much promise as a technique for improving fat graft take. However, the concentration of stromal vascular fraction cells required to optimally enhance fat graft retention remains unknown.Human lipoaspirate was processed for both fat transfer and harvest of stromal vascular fraction cells. Cells were then mixed back with fat at varying concentrations ranging from 10,000 to 10 million cells per 200 μl of fat. Fat graft volume retention was assessed by means of computed tomographic scanning over 8 weeks, and then fat grafts were explanted and compared histologically for overall architecture and vascularity.Maximum fat graft retention was seen at a concentration of 10,000 cells per 200 μl of fat. The addition of higher number of cells negatively impacted fat graft retention, with supplementation of 10 million cells producing the lowest final volumes, lower than fat alone. Interestingly, fat grafts supplemented with 10,000 cells showed significantly increased vascularity and decreased inflammation, whereas fat grafts supplemented with 10 million cells showed significant lipodegeneration compared with fat alone: The authors' study demonstrates dose dependence in the number of stromal vascular fraction cells that can be added to a fat graft to enhance retention. Although cell-assisted lipotransfer may help promote graft survival, this effect may need to be balanced with the increased metabolic load of added cells that may compete with adipocytes for nutrients during the postgraft period.

  View details for DOI 10.1097/PRS.0000000000001367

  View details for Web of Science ID 000357096300002

  View details for PubMedID 25829158

  View details for PubMedCentralID PMC4483157

• Emerging drugs for the treatment of wound healing EXPERT OPINION ON EMERGING DRUGS Zielins, E. R., Brett, E. A., Luan, A., Hu, M. S., Walmsley, G. G., Paik, K., Senarath-Yapa, K., Atashroo, D. A., Wearda, T., Lorenz, H. P., Wan, D. C., Longaker, M. T. 2015; 20 (2): 235-246

  Abstract

  Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process.A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed.The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

  View details for DOI 10.1517/14728214.2015.1018176

  View details for Web of Science ID 000356118400007

  View details for PubMedID 25704608

• Therapeutic Applications of Human Adipose-Derived Stromal Cells for Soft Tissue Reconstruction DISCOVERY MEDICINE Zielins, E. R., Luan, A., Brett, E. A., Longaker, M. T., Wan, D. C. 2015; 105: 245-253

  Abstract

  Adipose derived stromal cells (ASCs) are a multipotent cell population derived from the stromal vascular fraction of lipoaspirate. Given their relatively broad differentiation potential and paracrine capabilities, ASCs represent a readily accessible, endogenous resource for novel reconstructive strategies. In particular, augmentation of autologous fat grafts with ASCs has already been employed clinically for restoration of soft tissue defects. While fat grafting alone remains highly unpredictable, enrichment of fat with supplemental ASCs, also known as cell-assisted lipotransfer (CAL), has been shown to significantly enhance volume retention. How addition of these cells to fat grafts results in improved outcomes, however, remains poorly understood. Furthermore, the safety of CAL in the setting of prior malignancy and post-radiation wound beds has yet to be fully determined, an important consideration for its use in cancer reconstruction. Thus, further studies to determine the how and why behind the efficacy of CAL are necessary before it can be widely adopted as a safe and reliable surgical technique.

  View details for Web of Science ID 000356922200001

• Therapeutic applications of human adipose-derived stromal cells for soft tissue reconstruction. Discovery medicine Zielins, E. R., Luan, A., Brett, E. A., Longaker, M. T., Wan, D. C. 2015; 19 (105): 245-253

  Abstract

  Adipose derived stromal cells (ASCs) are a multipotent cell population derived from the stromal vascular fraction of lipoaspirate. Given their relatively broad differentiation potential and paracrine capabilities, ASCs represent a readily accessible, endogenous resource for novel reconstructive strategies. In particular, augmentation of autologous fat grafts with ASCs has already been employed clinically for restoration of soft tissue defects. While fat grafting alone remains highly unpredictable, enrichment of fat with supplemental ASCs, also known as cell-assisted lipotransfer (CAL), has been shown to significantly enhance volume retention. How addition of these cells to fat grafts results in improved outcomes, however, remains poorly understood. Furthermore, the safety of CAL in the setting of prior malignancy and post-radiation wound beds has yet to be fully determined, an important consideration for its use in cancer reconstruction. Thus, further studies to determine the how and why behind the efficacy of CAL are necessary before it can be widely adopted as a safe and reliable surgical technique.

  View details for PubMedID 25977187

• Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis. Journal of visualized experiments : JoVE Zielins, E. R., Tevlin, R., Hu, M. S., Chung, M. T., McArdle, A., Paik, K. J., Atashroo, D., Duldulao, C. R., Luan, A., Senarath-Yapa, K., Walmsley, G. G., Wearda, T., Longaker, M. T., Wan, D. C. 2015

  View details for DOI 10.3791/52181

  View details for PubMedID 25650785

• Isolation and enrichment of human adipose-derived stromal cells for enhanced osteogenesis. Journal of visualized experiments : JoVE Zielins, E. R., Tevlin, R., Hu, M. S., Chung, M. T., McArdle, A., Paik, K. J., Atashroo, D., Duldulao, C. R., Luan, A., Senarath-Yapa, K., Walmsley, G. G., Wearda, T., Longaker, M. T., Wan, D. C. 2015: 52181-?

  Abstract

  Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are considered the gold standard for stem cell-based tissue engineering applications. However, the process by which they must be harvested can be associated with significant donor site morbidity. In contrast, adipose-derived stromal cells (ASCs) are more readily abundant and more easily harvested, making them an appealing alternative to BM-MSCs. Like BM-MSCs, ASCs can differentiate into osteogenic lineage cells and can be used in tissue engineering applications, such as seeding onto scaffolds for use in craniofacial skeletal defects. ASCs are obtained from the stromal vascular fraction (SVF) of digested adipose tissue, which is a heterogeneous mixture of ASCs, vascular endothelial and mural cells, smooth muscle cells, pericytes, fibroblasts, and circulating cells. Flow cytometric analysis has shown that the surface marker profile for ASCs is similar to that for BM-MSCs. Despite several published reports establishing markers for the ASC phenotype, there is still a lack of consensus over profiles identifying osteoprogenitor cells in this heterogeneous population. This protocol describes how to isolate and use a subpopulation of ASCs with enhanced osteogenic capacity to repair critical-sized calvarial defects.

  View details for DOI 10.3791/52181

  View details for PubMedID 25650785

• Cloud-Based Applications for Organizing and Reviewing Plastic Surgery Content. Eplasty Luan, A., Momeni, A., Lee, G. K., Galvez, M. G. 2015; 15

  Abstract

  Cloud-based applications including Box, Dropbox, Google Drive, Evernote, Notability, and Zotero are available for smartphones, tablets, and laptops and have revolutionized the manner in which medical students and surgeons read and utilize plastic surgery literature. Here we provide an overview of the use of Cloud computing in practice and propose an algorithm for organizing the vast amount of plastic surgery literature. Given the incredible amount of data being produced in plastic surgery and other surgical subspecialties, it is prudent for plastic surgeons to lead the process of providing solutions for the efficient organization and effective integration of the ever-increasing data into clinical practice.

  View details for PubMedID 26576208

• Design and Focus Test of a Preconsultation Decision Aid for Breast Cancer Reconstruction Patients: A Quality Improvement Initiative. Eplasty Hui, K. J., Liu, X. X., Luan, A., Lee, G. K. 2015; 15

  Abstract

  To design, develop, and evaluate via focus group a preconsultation decision aid to improve patient satisfaction for breast reconstruction.The design of the decision aid was based on perceived patient needs, literature, existing decision aids, and current standard of breast cancer reconstruction treatment and consultation at Stanford. Our decision aid was designed to (1) reducing fear of the unknown in patients via providing a knowledge base that they can rely on, (2) helping patients identify their key breast reconstruction concerns, (3) addressing common patient concerns, (4) providing a framework to help patients identify the treatment option that may be right for them, and (5) promoting shared decision making. Physicians were consulted on the decision aid, following which a focus group was conducted for patient feedback.Interviewed patients (n = 12) were supportive of the decision aid initiative. Participants were especially pleased with the side-by-side comparison of surgical options and the parsimonious way information was represented. All patients before undergoing reconstruction (n = 3) requested the decision guide to reference at home. All interviewed patients believed information level was "about right."Decision aid was well received by patients in the focus group. As the initiative is for quality improvement, we saw no need to further delay the distribution of the decision aid. A pilot study will be conducted to evaluate whether our decision aid has an effect on patients' decision regret, stress, and anxiety.

  View details for PubMedID 26171096

• Cost-effectiveness of preoperative imaging for appendicitis after indeterminate ultrasonography in the second or third trimester of pregnancy. Obstetrics and gynecology Kastenberg, Z. J., Hurley, M. P., Luan, A., Vasu-Devan, V., Spain, D. A., Owens, D. K., Goldhaber-Fiebert, J. D. 2013; 122 (4): 821-829

  Abstract

  To assess the cost-effectiveness of diagnostic laparoscopy, computed tomography (CT), and magnetic resonance imaging (MRI) after indeterminate ultrasonography in pregnant women with suspected appendicitis.A decision-analytic model was developed to simulate appendicitis during pregnancy taking into consideration the health outcomes for both the pregnant women and developing fetuses. Strategies included diagnostic laparoscopy, CT, and MRI. Outcomes included positive appendectomy, negative appendectomy, maternal perioperative complications, preterm delivery, fetal loss, childhood cancer, lifetime costs, discounted life expectancy, and incremental cost-effectiveness ratios.Magnetic resonance imaging is the most cost-effective strategy, costing $6,767 per quality-adjusted life-year gained relative to CT, well below the generally accepted $50,000 per quality-adjusted life-year threshold. In a setting where MRI is unavailable, CT is cost-effective even when considering the increased risk of radiation-associated childhood cancer ($560 per quality-adjusted life-year gained relative to diagnostic laparoscopy). Unless the negative appendectomy rate is less than 1%, imaging of any type is more cost-effective than proceeding directly to diagnostic laparoscopy.Depending on imaging costs and resource availability, both CT and MRI are potentially cost-effective. The risk of radiation-associated childhood cancer from CT has little effect on population-level outcomes or cost-effectiveness but is a concern for individual patients. For pregnant women with suspected appendicitis, an extremely high level of clinical diagnostic certainty must be reached before proceeding to operation without preoperative imaging.

  View details for DOI 10.1097/AOG.0b013e3182a4a085

  View details for PubMedID 24084540

• Small Increases To Employer Premiums Could Shift Millions Of People To The Exchanges And Add Billions To Federal Outlays HEALTH AFFAIRS Austin, D. R., Luan, A., Wang, L. L., Bhattacharya, J. 2013; 32 (9): 1531-1537

  Abstract

  The Affordable Care Act will expand insurance coverage to more than twenty-five million Americans, partly through subsidized private insurance available from newly created health insurance exchanges for people with incomes of 133-400 percent of the federal poverty level. The act will alter the financial incentive structure for employers and influence their decisions on whether or not to offer their employees coverage. These decisions, in turn, will affect federal outlays and revenues through several mechanisms. We model the sensitivity of federal costs for the insurance exchange coverage provision of the Affordable Care Act using the nationally representative Medical Expenditure Panel Survey data set. We assess revenues and subsidy outlays for premiums and cost sharing for individuals purchasing private insurance through exchanges. Our findings show that changing theoretical premium contribution levels by just $100 could induce 2.25 million individuals to transition to exchanges and increase federal outlays by $6.7 billion. Policy makers and analysts should pay especially careful attention to participation rates as the act's implementation continues.

  View details for DOI 10.1377/hlthaff.2013.0522

  View details for Web of Science ID 000324681500004

  View details for PubMedID 24019356