Publications by authors named "Spencer A Brown"

88 Publications

Induction of Myogenic Differentiation Improves Chemosensitivity of Chemoresistant Cells in Soft-Tissue Sarcoma Cell Lines.

Sarcoma 2020 26;2020:8647981. Epub 2020 Mar 26.

Cooper University Hospital, Camden, NJ, USA.

Rhabdomyosarcoma (RMS) and rhabdoid tumors (RT) are rare soft-tissue malignancies with the highest incidence in infants, children, and adolescents. Advanced, recurrent, and/or metastatic RMS and RT exhibit poor response to treatment. One of the main mechanisms behind resistance to treatment is believed to be intratumoral heterogeneity. In this study, we investigated the myogenic determination factor 1 (MYOD1) and Noggin (NOG) markers in an embryonal RMS (ERMS) cell line and an RT cell line and the differential response of the MYOD1 and NOG expressing subpopulations to chemotherapy. Importantly, we found that these markers together identify a subpopulation of cells (MYOD1+ NOG+ cells) with primary resistance to Vincristine and Doxorubicin, two commonly used chemotherapies for ERMS and RT. The chemoresistant MYOD1+ NOG+ cells express markers of undifferentiated cells such as myogenin and ID1. Combination of Vincristine with TPA/GSK126, a drug combination shown to induce differentiation of RMS cell lines, is able to partially overcome MYOD1/NOG cells chemoresistance.
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http://dx.doi.org/10.1155/2020/8647981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136814PMC
March 2020

Locally Transplanted Adipose Stem Cells Reduce Anastomotic Leaks in Ischemic Colorectal Anastomoses: A Rat Model.

Dis Colon Rectum 2020 07;63(7):955-964

Department of Surgery, Cooper University Hospital, Camden, New Jersey.

Background: Anastomotic leakage remains a dreaded complication after colorectal surgery. Stem-cell-based therapies have been shown to increase angiogenesis and cell proliferation.

Objective: The purpose of this research was to investigate the use of adipose-derived stem cells on the healing of ischemic colonic anastomoses in a rat model.

Design: This is an animal research study using xenotransplantation.

Settings: Male Wistar rats (300-400 g, n = 48) were purchased from a licensed breeder.

Patients: Adipose stem cells were isolated from the subcutaneous fat of healthy human donors.

Interventions: The rats underwent laparotomy with creation of an ischemic colorectal anastomosis created by ligation of mesenteric vessels. The animals were divided into 3 groups: control group with an ischemic anastomosis, vehicle-only group in which the ischemic anastomosis was treated with an absorbable gelatin sponge, and a treatment group in which the ischemic anastomosis was treated with an absorbable gelatin sponge plus adipose stem cells. Animals were killed at postoperative days 3 and 7.

Main Outcome Measures: Anastomotic leakage was defined as the finding of feculent peritonitis or perianastomotic abscess on necropsy. Rat mRNA expression was measured using real-time polymerase chain reaction.

Results: Adipose-derived stem cells significantly decreased anastomotic leakage when compared with control at both postoperative days 3 (25.0% vs 87.5%; p = 0.02) and 7 (25.0% vs 87.5%; p = 0.02). The use of an absorbable gelatin sponge alone had no effect on anastomotic leakage when compared with control and postoperative days 3 or 7. We found that stem cell-treated animals had a 5.9-fold and 7.4-fold increase in the expression of vascular endothelial growth factor when compared with control at 3 and 7 days; however, this difference was not statistically significant when compared with the absorbable gelatin sponge group.

Limitations: This is a preclinical animal research study using xenotransplantation of cultured stem cells.

Conclusions: Locally transplanted adipose stem cells enhance the healing of ischemic colorectal anastomoses and may be a novel strategy for reducing the risk of anastomotic leakage in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B203. EL TRANSPLANTE LOCAL DE CÉLULAS MADRE ADIPOSAS REDUCE LA FUGA ANASTOMÓTICA EN LAS SUTURAS COLORRECTALES ISQUÉMICAS: MODELO EN RATAS: Las fugas anastomóticas son una complicación pusilánime después de toda cirugía colorrectal. Se ha demostrado que el tratamiento con células madre aumenta la angiogénesis y la proliferación celular.Investigar el uso de células madre derivadas de tejido adiposo en la cicatrización de una anastomosis colónica isquémica basada en ratas como modelo.Estudio de investigación en animales utilizando xenotrasplantes.Adquisición de típicas ratas de laboratorio raza Wistar, todas machos (300-400 g, n = 48) de un criadero autorizado.Aislamiento de células madre de tipo adiposo del tejido celular subcutáneo en donantes humanos sanos.Las ratas se sometieron a laparotomía con la creación de una anastomosis colorrectal isquémica obtenida mediante ligadura controlada de los vasos mesentéricos correspondientes. Los animales se dividieron en tres grupos: grupo de control con anastomosis isquémica, grupo de vehículo único en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible, y un grupo de tratamiento en el que la anastomosis isquémica se trató con una esponja de gelatina absorbible asociada a un vástago adiposo de células madre. Los animales fueron sacrificados el POD3 y el POD7.La fuga anastomótica fué definida como el hallazgo de peritonitis fecaloidea o absceso perianastomótico a la necropsia. La expresión de RNAm de las ratas se midió usando PCR en tiempo real.Las células madre derivadas de tejido adiposo disminuyeron significativamente la fuga anastomótica en comparación con el grupo control tanto en el POD3 (25% frente a 87.5%, p = 0.02) como en el POD7 (25% frente a 87.5%, p = 0.02). El uso de una esponja de gelatina absorbible sola, no tuvo efecto sobre la fuga anastomótica en comparación con los controles el POD3 o el POD7. Descubrimos que los animales tratados con células madre adiposas tenían un aumento de 5,9 y 7,4 veces en la expresión de VEGF en comparación con el control a los 3 y 7 días, respectivamente; sin embargo, esta diferencia no fue estadísticamente significativa en comparación con el grupo de esponja de gelatina absorbible.Este es un estudio preclínico de investigación en animales que utiliza xenotrasplantes de células madre adiposas cultivadas.Las células madre de tipo adiposo trasplantadas localmente mejoran la cicatrisación en casos de anastomosis colorrectales isquémicas, y podrían convertirse en una nueva estrategia para reducir el riesgo de fugas anastomóticas en casos de cirugía colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B203. (Traducción-Dr Xavier Delgadillo).
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http://dx.doi.org/10.1097/DCR.0000000000001667DOI Listing
July 2020

Changing the Paradigm of Craniofacial Reconstruction: A Prospective Clinical Trial of Autologous Fat Transfer for Craniofacial Deformities.

Ann Surg 2021 May;273(5):1004-1011

Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Objective: This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options.

Background: Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities.

Methods: In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9 ± 13.2 mL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment.

Results: No serious adverse events occurred. Volume retention averaged 63 ± 17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996, P < 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P = 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%, P = 0.009). Satisfaction with physical appearance (P = 0.002), social relationships (P = 0.02), and social functioning quality of life (P = 0.05) improved from baseline to 9 months.

Conclusions: For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.
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http://dx.doi.org/10.1097/SLA.0000000000003318DOI Listing
May 2021

Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum.

Int J Gynaecol Obstet 2019 May 15;145(2):225-232. Epub 2019 Mar 15.

Department of Surgical Research, Cooper University Hospital, Camden, NJ, USA.

Objective: To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov-3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance.

Methods: A pilot study was conducted in Cooper University Hospital, NJ, USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov-3. Omental adipose-derived stem cells (OASCs) were isolated from omentum with/without metastases. Caov-3 was cultured with OASCs' conditioned medium and subjected to different drugs. Cell viability and secretome was measured using MTT and Elisa, respectively.

Results: Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%-94% increased cytotoxicity against Caov-3 (P≤0.005). Metastatic OASCs conditioned medium showed up to 27-fold increase in tumorigenic factors and promoted chemoresistance (28%-35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40-fold reversal in this chemoresistance.

Conclusion: Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first-line chemotherapy.
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http://dx.doi.org/10.1002/ijgo.12800DOI Listing
May 2019

The Effect of the Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid and Paclitaxel Treatment on Full-Thickness Wound Healing in Mice.

Ann Plast Surg 2018 10;81(4):482-486

Hematology and Oncology, Cooper University Hospital, Camden, NJ.

Introduction: Neoadjuvant chemotherapy prior to lumpectomy or mastectomy for breast cancer challenges wound healing. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been shown to work synergistically with paclitaxel in vitro and in preclinical studies. In addition, our laboratory has demonstrated that SAHA treatment decreases paclitaxel-associated stem cell toxicity, modulates inflammatory response, and promotes wound healing in injured fibroblast cells. Our goal was to determine if combined SAHA and paclitaxel treatment would improve wound healing in an in vivo full-thickness murine model, without altering antitumor effect.

Methods: Thirty-two nude athymic mice received intraperitoneal injections of paclitaxel (20 mg/kg), SAHA (25 mg/kg), paclitaxel + SAHA (20 mg/kg + 25 mg/kg), or no treatment for 2 weeks prior to surgery. Under general anesthesia, 8-mm full-thickness dorsal wounds were created in all animals, and a silicone splint was attached to minimize wound contraction. The wounds were measured twice a week with a surgical caliper until healing was complete. To evaluate the in vivo effect of drug treatment, 16 athymic nude mice with MDA-MB-231 xenografts received the treatments described previously, following which tumor volumes were compared between groups.

Results: Average wound healing time was prolonged in mice treated with paclitaxel (20 ± 1.9 days), and combination SAHA + paclitaxel therapy improved average wound healing time (17.0 ± 1.8 days). In the xenograft model, the antitumor effect of SAHA and paclitaxel (average tumor volume 43.9 ± 34.1 mm) was greater than paclitaxel alone (105.8 ± 73.8 mm).

Conclusions: The addition of SAHA to taxane chemotherapy improves the therapeutic effect on triple-negative breast cancer while decreasing the detrimental effect of paclitaxel on wound healing. This may have substantial implications on improving outcomes in breast reconstruction following chemotherapy.
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http://dx.doi.org/10.1097/SAP.0000000000001519DOI Listing
October 2018

Spectral analysis of heart rate variability predicts mortality and instability from vascular injury.

J Surg Res 2018 04 22;224:64-71. Epub 2017 Dec 22.

Cooper University Hospital, Camden, New Jersey.

Background: Spectral analysis of continuous blood pressure and heart rate variability provides a quantitative assessment of autonomic response to hemorrhage. This may reveal markers of mortality as well as endpoints of resuscitation.

Methods: Fourteen male Yorkshire pigs, ranging in weight from 33 to 36 kg, were included in the analysis. All pigs underwent laparotomy and then sustained a standardized retrohepatic inferior vena cava injury. Animals were then allowed to progress to class 3 hemorrhagic shock and where then treated with abdominal sponge packing followed by 6 h of crystalloid resuscitation. If the pigs survived the 6 h resuscitation, they were in the survival (S) group, otherwise they were placed in the nonsurvival (NS) group. Fast Fourier transformation calculations were used to convert the components of blood pressure and heart rate variability into corresponding frequency classifications. Autonomic tones are represented as the following: high frequency (HF) = parasympathetic tone, low frequency (LF) = sympathetic, and very low frequency (VLF) = renin-angiotensin aldosterone system. The relative sympathetic to parasympathetic tone was expressed as LF/HF ratio.

Results: Baseline hemodynamic parameters were equal for the S (n = 11) and NS groups. LF/HF was lower at baseline for the NS group but was higher after hemorrhage and the resuscitation period indicative of a predominately parasympathetic response during hemorrhagic shock before mortality. HF signal was lower in the NS group during the resuscitation indicating a relatively lower sympathetic tone during hemorrhagic shock, which may have contributed to mortality. Finally, the NS group had a lower VLF signal at baseline (e.g., [S] 16.3 ± 2.5 versus [NS] 4.6 ± 2.9 P < 0.05,) which was predictive of mortality and hemodynamic instability in response to a similar hemorrhagic injury.

Conclusions: An increased LF/HF ratio, indicative of parasympathetic predominance following injury and during resuscitation of hemorrhagic shock was a marker of impending death. Spectral analysis of heart rate variability can also identify autonomic lability following hemorrhagic injuries with implications for first responder triage. Furthermore, a decreased VLF signal at baseline indicates an additional marker of hemodynamic instability and marker of mortality following a hemorrhagic injury. These data indicate that continuous quantitative assessment of autonomic response can be a predictor of mortality and potentially guide resuscitation of patients in hemorrhagic shock.
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http://dx.doi.org/10.1016/j.jss.2017.11.029DOI Listing
April 2018

Human adipose-derived stem cell treatment modulates cellular protection in both in vitro and in vivo traumatic brain injury models.

J Trauma Acute Care Surg 2018 05;84(5):745-751

From the Department of Surgery (N.S.K., S.C., W.M.H., M.P., T.O., P.Z., J.P.C., S.A.B.), Cooper University Hospital, Camden, NJ; and Division of Trauma (J.P.H.), Cooper University Hospital, Camden, NJ.

Background: Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study was to examine the effect(s) of adipose-derived stem cell (ASC) treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods.

Methods: Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC-conditioned medium (CM) on cell death, mitochondrial function, and expression of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1β [IL-1β], and IL-6), as well as apoptosis marker FAS, was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed-head injury model. Animals randomly received either intravenous human-derived ASCs or intravenous saline within 3 hours of injury and were compared with a sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI Day 3, brain tissue was harvested and assessed for cellular damage via enzyme-linked immunosorbent assay for TNF-α, as well as immunohistochemical staining for β-amyloid precursor protein (β-APP).

Results: Our in vitro data show that ASC treatment imparted reduced cell death (ratio to control: 1.21 ± 0.066 vs. 1.01 ± 0.056, p = 0.017), increased cell viability (ratio to control: 0.86 ± 0.009 vs. 1.09 ± 0.01, p = 0.0001), increased mitochondrial function (percentage of control: 78 ± 6% vs. 68 ± 3%), and significantly decreased levels of inflammatory cytokine IL-1β. In our in vivo study, compared with TBI alone, ASC-treated animals showed no difference in functional recovery, lower levels of expressed TNF-α (ratio to total protein, 0.47 ± 0.01 vs. 0.67 ± 0.04; p < 0.01), and lower levels of β-amyloid precursor protein (fluorescence ratio, 0.43 ± 0.05 vs. 0.69 ± 0.03; p < 0.01).

Conclusions: Adipose-derived stem cell treatment results in improved cell survival, decreased inflammatory marker release, and decreased evidence of neural injury. No difference in functional recovery was seen. These data suggest the potential for ASC treatment to aid in cellular protection and recovery in neural cells following TBI.
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http://dx.doi.org/10.1097/TA.0000000000001770DOI Listing
May 2018

The endothelial cell secretome as a novel treatment to prime adipose-derived stem cells for improved wound healing in diabetes.

J Vasc Surg 2018 07 29;68(1):234-244. Epub 2017 Jul 29.

Department of Surgery, Cooper University Hospital, Camden, NJ. Electronic address:

Background: Chronic wounds are a common surgical problem exacerbated by diabetes and ischemia. Although adipose-derived stem cells (ASCs) have shown promise as a wound healing therapy, their function and proliferation are hindered in diabetes. This study examines the ability of the human umbilical vein endothelial cell (HUVEC) secretome to reverse the deleterious effects of high glucose concentrations on ASCs through priming, thereby enhancing their ability to participate in angiogenesis and wound healing.

Methods: Institutional review board-approved human ASCs were cultured in M199 medium with or without glucose (30 mmol/L). HUVEC were grown in 30 mmol/L glucose-containing M199 medium; the resulting conditioned medium (HUVEC-CM) was collected every 3 days and used to prime ASCs. An aliquot of HUVEC-CM was heated (85°C for 30 minutes) to produce thermal denaturation of protein. Viability, proliferation, and endothelial differentiation were measured by MTT assays, growth curves, and quantitative polymerase chain reaction, respectively. A Matrigel assay was used to assess the ability of primed ASCs to participate in capillary-like tube formation. An Institutional Animal Care and Use Committee-approved in vivo murine model of diabetic and ischemic hindlimbs was used to evaluate the angiogenic potential of primed stem cells. Human ASCs were cultured with either control M199 or HUVEC-CM. Mice were randomized to a control group, an unprimed ASC group, or a HUVEC-primed ASC group. Cellular therapies were injected into the ischemic muscle. Thirty days later, slides were made. Microvessels were counted by three blinded observers.

Results: MTT assays revealed that HUVEC-priming induced a 1.5 times increase in cell viability over diabetic controls. This promoting effect was lost with heated HUVEC-CM (P < .001), indicating that the active molecules are of protein origin. After 9 days, ASCs cultured in 30 mmol/L glucose solution showed a 14% reduction in growth from nondiabetic controls (P = .013) and exhibited atrophic morphology. Conversely, diabetic HUVEC-primed stem cells demonstrated a nearly four-fold increase in proliferation (P < .05) and took on a fusiform, endothelial-like phenotype. Polymerase chain reaction demonstrated enhanced expression of CD31 messenger RNA by 4.7-fold after 14 days in the HUVEC-primed group, and endothelial nitric oxide synthase messenger RNA messenger RNA was increased 20.1-fold from controls. Unlike unprimed controls, HUVEC-primed ASCs readily formed capillary-like tube networks on Matrigel. Diabetic mice that were injected with HUVEC-primed ASCs demonstrated greater vessel density than both controls (2.1-fold) and unprimed stem cell treatments (P < .001).

Conclusions: HUVECs secrete protein factors that significantly increase proliferation and endothelial differentiation of ASCs under diabetic conditions. Injection of ischemic hindlimbs in diabetic mice with HUVEC-primed ASCs leads to enhanced angiogenesis.
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http://dx.doi.org/10.1016/j.jvs.2017.05.094DOI Listing
July 2018

Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While Preserving the Wound-Healing Function of Adipose-Derived Stem Cells.

Ann Plast Surg 2017 Jun;78(6):728-735

From the *Cooper University Hospital; and †Cooper Medical School of Rowan University, Camden, NJ.

Introduction: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications.

Methods: Triple negative breast cancer cells (MBA-MB-231) and hASCs (institutional review board-approved clinical isolates) were treated with a standard therapeutic dose of paclitaxel (1.0 μM) or with low-dose paclitaxel (0.1 μM) combined with the HDACi suberoylanilide hydroxamic acid or trichostatin A. Cell viability, gene expression, apoptosis, and wound-healing/migration were measured via methylthiazol tetrazolium assay, quantitative real-time polymerase chain reaction, annexin V assay, and fibroblast scratch assay, respectively.

Results: Combined HDACi and low-dose paclitaxel therapy maintained cytotoxicity towards breast cancer cells and preserved adipose-derived stem cell viability. Histone deacetylase inhibitor demonstrated selective anti-inflammatory effects on adipose-derived stem cell gene expression and decreased expression of the proapoptotic gene FAS. Furthermore, HDACi therapy did not increase relative apoptosis within hASCs. A scratch assay demonstrated enhanced wound healing among injured fibroblasts indirectly co-cultured with HDACi-treated hASCs.

Conclusions: Combining HDACi with low-dose paclitaxel improved cytotoxicity towards breast cancer cells and preserved hASC viability. Furthermore, enhanced wound healing was observed by improved migration in a fibroblast scratch assay. These results suggest that the addition of HDACi to taxane chemotherapy regimens may improve oncologic results and wound-healing outcomes after reconstructive surgery.
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http://dx.doi.org/10.1097/SAP.0000000000001066DOI Listing
June 2017

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

J Trauma Acute Care Surg 2017 07;83(1):71-76

From the Cooper University Hospital (K.R.K., B.M.M., J.P.G., R.S.N., M.W.F., A.L., R.H., R.L.C., S.A.B., J.P.H.), Camden, New Jersey.

Background: Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone.

Methods: Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant.

Results: There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05).

Conclusion: These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model.

Level Of Evidence: This is basic science research based on a large animal model, level V.
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http://dx.doi.org/10.1097/TA.0000000000001492DOI Listing
July 2017

Evaluation of function and recovery of adipose-derived stem cells after exposure to paclitaxel.

Cytotherapy 2017 02 22;19(2):211-221. Epub 2016 Nov 22.

Department of Surgery, Cooper University Hospital, Camden, New Jersey, USA.

Background Aims: Adipose-derived stem cells (ASCs) are considered to play a positive role in wound healing as evidenced by their increasing use in breast reconstructive procedures. After chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. In the present study, the functional capabilities and recovery of ASCs after exposure to chemotherapeutic agent paclitaxel (PTX) using in vitro and ex vivo models were demonstrated.

Methods: Human ASCs were isolated from periumbilical fat tissue and treated with PTX at various concentrations. Adult Sprague-Dawley rats were given intravenous injections with PTX. Two and four weeks after the initial PTX treatment, ASCs were isolated from rat adipose tissue. Proliferation, cell viability, apoptosis and cell migration rates were measured by growth curves, MTT assays, flow cytometry and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX for 3 weeks. Adipogenic, osteogenic and endothelial differentiation levels were measured by quantitative reverse transcriptase polymerase chain reaction and histological staining.

Results: PTX induced apoptosis, decreased the proliferation and cell migration rates of ASCs and inhibited ASCs multipotent differentiation in both in vitro human ASC populations and ex vivo rat ASC populations with PTX treatment. Furthermore, after cessation of PTX, ASCs exhibited recovery potential of differentiation capacity in both in vitro and animal studies.

Conclusions: Our results provide insight into poor soft tissue wound healing and promote further understanding of the potential capability of ASCs to serve as a cell source for fat grafting and reconstruction in cancer patients undergoing chemotherapy treatment.
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http://dx.doi.org/10.1016/j.jcyt.2016.10.010DOI Listing
February 2017

Fibroblast growth factor and vascular endothelial growth factor play a critical role in endotheliogenesis from human adipose-derived stem cells.

J Vasc Surg 2017 05 8;65(5):1483-1492. Epub 2016 Aug 8.

Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ. Electronic address:

Objective: Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in patients with critical limb ischemia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) play a major role in angiogenesis and wound healing. This study evaluated the effects of FGF and VEGF on the proliferation, migration, and potential endothelial differentiation of human ASCs with regards to their use as endothelial cell substitutes.

Methods: ASCs were isolated from clinical lipoaspirates and cultured in M199 medium with fetal bovine serum (10%), FGF2 (10 ng/mL), VEGF (50 ng/mL), or combinations of FGF2 and VEGF. Cell proliferation rates, viability, and migration were measured by growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and scratch assays. For cell attachment determinations, ASCs were seeded onto a scaffold of small intestinal submucosa for 5 days. Endothelial differentiation capabilities of ASCs were confirmed by expression of endothelial cell-specific markers using quantitative polymerase chain reaction, immunofluorescence staining, and cord formation on Matrigel (BD Biosciences, San Jose, Calif). PD173074, a selective inhibitor of FGF receptor, was used to confirm the importance of FGF signaling.

Results: ASCs treated with FGF or combinations of FGF and VEGF showed increased proliferation rates and consistent differentiation toward an endothelial cell lineage increase in platelet endothelial cell adhesion molecule (CD31), von Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial cadherin message, and in protein and cord formation on Matrigel. FGF and VEGF stimulated ASC migration and increased the attachment and retention after seeding onto a matrix graft of small intestinal submucosa. Blockade of FGF signaling with PD173074 abrogated ASC endothelial cell differentiation potential.

Conclusions: These results indicate that FGF and VEGF are ASC promoters for proliferation, migration, attachment, and endothelial differentiation. FGF and VEGF have a costimulatory effect on ASC endotheliogenesis. These results further suggest that ASCs with enhanced FGF signaling may potentially be used for tissue engineering and cell-based therapies in patients with critical limb ischemia.
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http://dx.doi.org/10.1016/j.jvs.2016.04.034DOI Listing
May 2017

In vitro effects of tamoxifen on adipose-derived stem cells.

Wound Repair Regen 2015 Sep 14;23(5):728-36. Epub 2015 Jul 14.

Department of Surgery, Cooper University Hospital, Camden, New Jersey.

In breast reconstructive procedures, adipose-derived stem cells (ASCs) that are present in clinical fat grafting isolates are considered to play the main role in improving wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. However, it is unclear if tamoxifen (TAM) as the most widely used hormonal therapeutic agent for breast cancer treatment, affects the ASCs and ultimately wound healing. This study evaluated whether TAM exposure to in vitro human ASCs modulate cellular functions. Human ASCs were isolated and treated with TAM at various concentrations. The effects of TAM on cell cycle, cell viability and proliferation rates of ASCs were examined by growth curves, MTT assay and BrdU incorporation, respectively. Annexin V and JC-1 Mitochondrial Membrane Potential assays were used to analyze ASC apoptosis rates. ASCs were cultured in derivative-specific differentiation media with or without TAM (5 uM) for 3 weeks. Adipogenic and osteogenic differentiation levels were measured by quantitative RT-PCR and histological staining. TAM has cytotoxic effects on human ASCs through apoptosis and inhibition of proliferation in dose- and time-dependent manners. TAM treatment significantly down-regulates the capacity of ASCs for adipogenic and osteogenic differentiation (p<0.05 vs. control), and inhibit the ability of the ASCs to subsequently formed cords in Matrigel. This study is the first findings to our knowledge that demonstrated that TAM inhibited ASC proliferation and multi-lineage ASC differentiation rates. These results may provide insight into the role of TAM with associated poor soft tissue wound healing and decreased fat graft survival in cancer patients receiving TAM.
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http://dx.doi.org/10.1111/wrr.12322DOI Listing
September 2015

Mechanical performance of surgical knots in a vaginal surgery model.

J Surg Educ 2013 May-Jun;70(3):340-4. Epub 2013 Feb 13.

Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.

Objective: To evaluate the integrity of 3 different types of sliding knots in a vaginal surgery model.

Study Design: Nonidentical sliding (NS), loop-to-strand sliding (LTS), and parallel sliding (PS) knots with 4 throws each were tied on a vaginal surgery model with 0 polyglactin-910 and tested until failure. The main outcomes studied were the maximum load reached at failure and the proportion of each type of sliding knot that either unraveled or broke during standardized laboratory testing.

Results: PS knots were significantly stronger than either NS or LTS knots, with no difference in strength between NS and LTS knots. Most of the NS and LTS knots failed by slippage, where as most of the PS knots failed by rupture at the knot site.

Conclusions: PS knots using 0-vicryl are significantly stronger than NS and LTS knots and should be preferentially considered when performing vaginal surgery.
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http://dx.doi.org/10.1016/j.jsurg.2012.11.010DOI Listing
January 2014

Commentary on: Metabolic and structural effects of phosphatidylcholine and deoxycholate injections on subcutaneous fat: a randomized, controlled trial.

Authors:
Spencer A Brown

Aesthet Surg J 2013 Mar;33(3):409-10

Center for Innovation in Restorative Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1177/1090820X13478631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667692PMC
March 2013

Surgical knot integrity: effect of suture type and caliber, and level of residency training.

J Surg Educ 2013 Jan-Feb;70(1):156-60. Epub 2012 Aug 14.

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.

Objective: To evaluate if suture type and caliber or level of residency training affects strength and mode of failure of surgical knots.

Design: All residents in an obstetrics and gynecology training program were invited to tie knots on a bench model using 2 calibers (0 and 3-0) of 2 types of surgical suture (polyglactin 910 and polydioxanone). The failure load, mode of failure, and loop lengths of the knots were determined.

Setting: University of Texas Southwestern Medical Center, Dallas, Texas.

Participants: Physicians enrolled in the University of Texas Southwestern Medical Center Obstetrics and Gynecology residency training program.

Results: Seventy-one of 73 residents participated. Knots tied with 0-caliber sutures had a higher mean failure load than those tied with 3-0 caliber sutures. For each type and caliber of suture, there were no differences in failure load between each level of residency training. However, senior residents tied knots with shorter loop lengths and had a lower proportion of knots that unraveled or slipped.

Conclusions: Even though there were no differences in failure loads, senior residents tied tighter and more secure knots than their junior counterparts.
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http://dx.doi.org/10.1016/j.jsurg.2012.06.028DOI Listing
August 2013

Transdermal delivery of adipocyte-derived stem cells using a fractional ablative laser.

Aesthet Surg J 2013 Jan;33(1):109-16

Department of Plastic Surgery, University of Texas Southwestern Medical Center in Dallas, TX 75390-9132, USA.

Background: Chronic wound healing problems can pose a significant clinical challenge. Transdermal delivery of adipose-derived stem cells (ADSC) may be a possible solution to healing these recalcitrant, debilitating wounds. Pretreatment of the skin with a fractionated laser has already been shown to assist transdermal drug delivery both in vitro and in vivo and may be an ideal approach to facilitating delivery of ADSC to the target tissue.

Objectives: The authors investigate in a porcine model whether ADSC can be delivered transdermally following pretreatment with a fractional laser.

Methods: After ethics approval was obtained, the abdomens of 2 adult female domestic pigs were pretreated with an erbium:YAG fractionated ablative laser. Following laser treatment, 20 × 10(6) bromodeoxyuridine (BrdU)-labeled ADSC were applied topically to the first animal for 4 hours. The same number of BrdU-labeled ADSC was applied to the second animal for 48 hours. The animals were euthanized at the end of their respective treatment periods, and the BrdU-labeled ADSC were counted after tissue harvest.

Results: At 4 hours, an average of 2.40 × 10(6) cells, or 12.0% of the total cells applied, were found in the tissue. At 48 hours, an average of 1.1 × 10(6) cells, or 5.5% of the total cells applied, were seen.

Conclusions: This pilot study demonstrates that ADSC can be delivered transdermally through skin that has been pretreated with a laser. Potential future applications of this approach might include wound-healing or aesthetic indications. Further studies need to be conducted to determine the optimal number of ADSC to use in this approach, the best methods of application, and the effect of transdermally delivered ADSC on wound healing.
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http://dx.doi.org/10.1177/1090820X12469222DOI Listing
January 2013

Subcutaneous fat tissue engineering using autologous adipose-derived stem cells seeded onto a collagen scaffold.

Plast Reconstr Surg 2012 Dec;130(6):1208-1217

Dallas, Texas; and Lyon, France From the Department of Plastic Surgery, University of Texas Southwestern Medical Center; Banque de Tissus et de Cellules, Hôpital Edouard Herriot; and the Department of Plastic Surgery, Hospices Civils de Lyon, Université Claude Bernard Lyon.

Background: This pilot study examined the efficacy of 5-bromo-2-deoxyuridine-labeled autologous adipose-derived stem cells seeded onto collagen scaffolds to augment and/or regenerate the fat-enriched hypodermal tissue in an acute porcine wound model.

Methods: Porcine autologous adipose-derived stem cells were isolated and cultured. At passage 2, the cells were labeled with 5-bromo-2-deoxyuridine, seeded onto a three-dimensional collagen scaffold, and cultured for 10 days. Scaffolds were implanted subcutaneously in adult pigs with two adipose-derived stem cell scaffolds and two control scaffolds. Animals were euthanized at 2, 4, 8, and 12 weeks; all scaffold conditions were explanted for histology and immunohistochemistry analyses.

Results: For all time points, adipose-derived stem cell scaffolds had increased connective tissue matrix within the subcutaneous tissue compared with scaffold alone and untreated porcine skin (p < 0.01). The neosynthesized connective tissue was vascularized and composed of small cells within an abundant extracellular matrix organized in layers. 5-Bromo-2-deoxyuridine cells were detectable only up to 4 weeks and mature adipocytes were absent. Levels of collagen types I, III, and VI differed among the experimental groups, with increased extracellular matrix associated with the presence of adipose-derived stem cells.

Conclusions: The authors' data clearly show the efficacy of adipose-derived stem cells for soft-tissue repair and skin aging because it induces a significant increase of the dermis thickness. Moreover, the authors' results demonstrate the interest of their acute wound model and allowed them to show the skin thickness variation over time of the experiment, which is one of the challenges with which clinicians struggle in fat grafting.
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http://dx.doi.org/10.1097/PRS.0b013e31826d100eDOI Listing
December 2012

A comparison between barbed and nonbarbed absorbable suture for fascial closure in a porcine model.

Plast Reconstr Surg 2012 Oct;130(4):535e-540e

Dallas, Texas; and Pittsburgh, Pa. From the Department of Plastic Surgery, University of Texas Southwestern Medical Center, and the Center for Innovation in Restorative Medicine, Division of Plastic Surgery, University of Pittsburgh.

Background: The use of knotless barbed sutures has shortened operation times for wound closure. In experimental models, their use in tendon surgery is still under investigation. This study looks at the use of barbed sutures in a porcine model for fascial repair when compared with traditional absorbable suture to further extend their clinical use.

Methods: Six animals were included in this study. Each had two paramedian incisions, down to the fascia at the junction between the lateral edge of the rectus abdominis muscle and the transverse abdominis/oblique muscles of the abdominal wall. One fascial incision was closed with 2-0 Quill polydioxanone barbed suture and the other was closed with the control suture 1-0 PDS II (polydioxanone). The overlying skin was closed with Quill polydioxanone barbed suture for both incisions. At 6 weeks, the fascia was excised and the suture lines were tested for tensile strength.

Results: There were no wound infections and no incisional hernias. The Quill polydioxanone barbed suture had a mean tissue tensile strength of 265.59 N (range, 206.86 to 306.38 N) and the control suture (polydioxanone) had a mean tissue tensile strength of 227.28 N (range, 132.79 to 290.35 N). The difference was not statistically significant (p = 0.341).

Conclusions: This study demonstrated that barbed sutures for fascial repair have equivalent tensile strength when compared with traditional nonbarbed sutures, with no adverse events such as wound dehiscence or incisional hernia. This preclinical study lends support to the practice of using barbed sutures for indications such as rectus sheath plication.
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http://dx.doi.org/10.1097/PRS.0b013e318262f0f6DOI Listing
October 2012

Fat grafting: evidence-based review on autologous fat harvesting, processing, reinjection, and storage.

Plast Reconstr Surg 2012 Jul;130(1):249-258

Dallas, Texas; and Lyon, France From the Departments of Plastic Surgery of University of Texas Southwestern Medical Center and Edouard Herriot Hospital, University of Lyon.

Background: Over the past 20 years, there has been a dramatic increase in the use of autologous fat grafting to treat volume and contour defects in aesthetic and reconstructive surgery. It is generally accepted that fat grafting is safe, with good patient satisfaction. However, there are many procedural variations, and in terms of objective clinical effectiveness, the major disadvantage of this technique remains the unpredictable fat resorption rates and subsequent adverse events. Because of the rapidly evolving nature of this procedure, this review article provides an update on previous reviews by looking at the current evidence base regarding fat graft techniques and their effect on clinical outcome.

Methods: A systematic review of the scientific literature listed on PubMed was performed using 20 search terms focused on harvesting, processing, reinjection, and conservation of fat grafting. An evidence-based system was used to determine eligibility for clinical and preclinical studies.

Results: Thirty-seven articles were selected based on inclusion and exclusion criteria: five articles were clinical trials and 32 were experimental comparative studies examining human fat grafting.

Conclusions: This systematic review revealed a lack of high-quality data despite the increase in fat grafting over the past 20 years. At present, there is no evidence that supports specific procedural standardization. Evidence-based studies that incorporate randomized controlled, prospective, multicenter trials are required to understand which factors influence positive fat grafting clinical outcomes.
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http://dx.doi.org/10.1097/PRS.0b013e318254b4d3DOI Listing
July 2012

Human adipose stem cells: current clinical applications.

Plast Reconstr Surg 2012 Jun;129(6):1277-1290

Dallas, Texas; and Lyon, France From the Department of Plastic Surgery, University of Texas Southwestern Medical Center, and the Department of Plastic Surgery, Edouard Herriot Hospital, University of Lyon.

Adipose-derived stem cells are multipotent cells that can easily be extracted from adipose tissue, are capable of expansion in vitro, and have the capacity to differentiate into multiple cell lineages, which have the potential for use in regenerative medicine. However, several issues need to be studied to determine safe human use. For example, there are questions related to isolation and purification of adipose-derived stem cells, their effect on tumor growth, and the enforcement of U.S. Food and Drug Administration regulations. Numerous studies have been published, with the interest in the potential for regenerative medicine continually growing. Several clinical trials using human adipose stem cell therapy are currently being performed around the world, and there has been a rapid evolution and expansion of their number. The purpose of this article was to review the current published basic science evidence and ongoing clinical trials involving the use of adipose-derived stem cells in plastic surgery and in regenerative medicine in general. The results of the studies and clinical trials using adipose-derived stem cells reported in this review seem to be promising not only in plastic surgery but also in a wide variety of other specialties. Nevertheless, those reported showed disparity in the way adipose-derived stem cells were used. Further basic science experimental studies with standardized protocols and larger randomized trials need to be performed to ensure safety and efficacy of adipose-derived stem cells use in accordance with U.S. Food and Drug Administration guidelines.
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http://dx.doi.org/10.1097/PRS.0b013e31824ecae6DOI Listing
June 2012

An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy.

Radiat Oncol 2012 May 8;7:68. Epub 2012 May 8.

1Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Purpose: To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.

Methods: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.

Results: No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.

Conclusions: We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.
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http://dx.doi.org/10.1186/1748-717X-7-68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403853PMC
May 2012

Developing business opportunities from concept to end point for craniofacial surgeons.

Authors:
Spencer A Brown

J Craniofac Surg 2012 Jan;23(1):298-300

Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Craniofacial surgeons repair a wide variety of soft and hard tissues that produce the clinical expertise to recognize the need for an improved device or novel regenerative stem cell or use of molecules that may dramatically change the way clinical care for improved patient outcomes. The business pathway to bring a concept to clinical care requires knowledge, mentoring, and a team of experts in business and patent law.
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http://dx.doi.org/10.1097/SCS.0b013e318241dccbDOI Listing
January 2012

Can fractional lasers enhance transdermal absorption of topical lidocaine in an in vivo animal model?

Lasers Surg Med 2012 Feb 2;44(2):168-74. Epub 2012 Feb 2.

Plastic Surgery Department, UT Southwestern Medical Center, Dallas, Texas, USA.

Background And Objective: It has been shown in vitro that pretreatment of skin with fractional lasers enhances transdermal delivery of drugs. The aim of this study is to demonstrate in vivo firstly that laser enhances transdermal drug absorption and secondly that this can be manipulated by altering laser settings.

Study Design/materials And Methods: Four pigs were used in the IACUC approved animal study. On day 0, 5 g of 4% topical lidocaine was applied under occlusion for 60 minutes to a 400 cm(2) area on the abdomen. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. On day 7, the Er:YAG laser was used at 500, 250, 50, and 25 µm ablative depth, respectively, over a 400 cm(2) area on the abdomen. Five grams of 4% topical lidocaine was applied immediately with occlusion for 60 minutes, and then removed. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. The serum was extracted and analyzed for lidocaine and its metabolite monoethylglycinexylidide (MEGX).

Results: Serum levels of lidocaine and MEGX were undetectable in untreated skin. Following laser treatment both lidocaine and MEGX were detectable. Peak levels of lidocaine were significantly higher (P = 0.0002) at 250 µm (0.62 mg/L), compared to 500 µm (0.45 mg/L), 50 µm (0.48 mg/L), and 25 µm (0.3 mg/L). Peak levels of MEGX were significantly higher (P ≤ 0.0001) at 250 µm (0.048 mg/L), compared to 500 µm (0.018 mg/L), 50 µm (0.036 mg/L), and 25 µm (0.0144 mg/L).

Conclusions: This study demonstrates that laser pretreatment significantly increases absorption of topical lidocaine so that it is detectable in the blood and that manipulating laser settings can affect drug absorption. Future work will look at translating this effect into clinical benefit.
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http://dx.doi.org/10.1002/lsm.21130DOI Listing
February 2012

An in vivo histopathological comparison of single and double pulsed modes of a fractionated CO(2) laser.

Lasers Surg Med 2012 Jan 3;44(1):4-10. Epub 2012 Jan 3.

Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9132, USA.

Introduction: Studies examining the histopathological changes that occur in human skin following fractional laser treatment have been performed mainly in animals or abdominal tissue prior to abdominoplasty. This study looks at the effect of double pulse fractional CO(2) laser compared to single pulse treatments to assess differences in tissue injury in the face and abdomen.

Methods: Twelve healthy subjects randomized into two groups, had two 1 cm(2) areas (infraumbilical and forehead) treated with the fractional CO(2) laser (Deep Fx, Lumenis). Settings used were 15 mJ double pulse, and 30 mJ single pulse, 300 Hz, 10% density and compared to the historic control of 15 patients treated at 15 mJ single pulse [Bailey et al. (2011), Lasers Surg Med 43: 99-107]. Treated sites were biopsied and analyzed with H&E and TUNEL staining to measure width and depth of the microthermal zones (MTZ) of ablation.

Results: When comparing 15 mJ double pulse to single pulse there were significant differences both in depth (abdominal skin, P = 0.002 and facial skin, P = 0.001) and width (facial skin, P = 0.0002) of MTZ. When comparing double pulsing at 15 mJ with single pulsing at 30 mJ there were significant differences between MTZ depths in the abdomen (P < 0.01) but not in either the MTZ depth (P = 0.69) or the width in the face (P = 0.502).

Discussion: This study demonstrates the differences between histopathological laser injury patterns in the face compared to the abdomen when single pulsing is used. It also demonstrates that double pulsing at 15 mJ is statistically similar to single pulsing at 30 mJ in the face. We think this could have ramifications for clinical practice where by double pulsing at lower energies may result in better clinical outcomes than increasing energies or using multiple passes at single pulse. Clinical studies needs to be performed to investigate this further.
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http://dx.doi.org/10.1002/lsm.21150DOI Listing
January 2012

The use of non-invasive instruments in characterizing human facial and abdominal skin.

Lasers Surg Med 2012 Feb 16;44(2):131-42. Epub 2011 Dec 16.

General Surgery Department, UT Southwestern Medical Center, Dallas, Texas 75392, USA.

Background And Objective: The skin is highly variable. This variation, although helpful for function, causes inconsistencies when assessed using subjective scales. The purpose of this study is to measure differences in skin on the face and abdomen using non-invasive, objective devices as a method to eliminate subjective error and help reduce intra- and inter-observer variability in clinical analysis.

Study Design/materials And Methods: Eighty-eight subjects between the ages of 18 and 61 were enrolled in this study. These subjects varied in age, ethnicity, and Fitzpatrick score. Facial analysis was performed by clinical evaluation and utilizing non-invasive objective devices which included the DermaScan C 20 MHz HFUS (Cyberderm, Broomall, PA), Tru Vu (Johnson and Johnson), BTC 2000 (SRLI Technologies, Nashville, TN), Derma Unit SSC3 (CK Electronic, Köln, Germany), and the Chromometer.

Results: Non-invasive devices were shown to be consistent and accurate through repeated measurement at each of the anatomical points with error rates of less than 5%. Chromometer measurements were able to categorize patients into Fitzpatrick level. DermaScan measurements demonstrated decreasing skin thicknesses associated with increasing age, smoking, and female gender. Derma Unit SSC 3 showed gender and sun exposure related differences in sebum concentration, pH, and moisture content. The Derma Unit SSC 3 sebum concentration also showed correlation with Tru Vu readings for clogged pores and bacterial activity.

Conclusion: The skin assessment scales that are in use today are often prone to variability and inaccuracy due to their subjectivity. Use of the described objective non-invasive facial analysis method provides an accurate, objective analysis of human skin which can be used to measure changes pre- and post-operatively, or even screen patients prior to procedure to identify non-responders or those prone to adverse events. Utilization of these devices introduces a foundation on which a strong evidence-based approach to aesthetic medicine can be built.
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http://dx.doi.org/10.1002/lsm.21147DOI Listing
February 2012

Animal model of implant capsular contracture: effects of chitosan.

Aesthet Surg J 2011 Jul;31(5):540-50

Faculty of Medicine, University of Porto, Hospital de São João, Serviço de Cirurgia Plástica, 4202-451 Porto, Portugal.

Background: The mechanism(s) responsible for breast capsular contracture (CC) remain unknown, but inflammatory pathways play a role. Various molecules have been attached to implant shells in the hope of modifying or preventing CC. The intrinsic antibacterial and antifungal activities of chitosan and related oligochitosan molecules lend themselves well to the study of the infectious hypothesis; chitosan's ability to bind to growth factors, its hemostatic action, and its ability to activate macrophages, cause cytokine stimulation, and increase the production of transforming growth factor (TGF)-β1 allow study of the hypertrophic scar hypothesis.

Objective: The authors perform a comprehensive evaluation, in a rabbit model, of the relationship between CC and histological, microbiological, and immunological characteristics in the presence of a chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC).

Methods: Eleven adult New Zealand rabbits were each implanted with three silicone implants: a control implant, one impregnated with COS, and one impregnated with LMWC. At four-week sacrifice, microdialysates were obtained in the capsule-implant interfaces for tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) level assessment. Histological and microbiological analyses were performed.

Results: Baker grade III/IV contractures were observed in the LMWC group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p < .05) compared to control and COS groups. Capsule tissue bacterial types and microdialysate TNF-α levels were similar among all groups.

Conclusions: Chitosan-associated silicone implantation in a rabbit model resulted in Baker grade III/IV CC. This preclinical study may provide a model to test various mechanistic hypotheses of breast capsule formation and subsequent CC.
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http://dx.doi.org/10.1177/1090820X11411475DOI Listing
July 2011

Dorsal aesthetic lines in rhinoplasty: a quantitative outcome-based assessment of the component dorsal reduction technique.

Plast Reconstr Surg 2011 Jul;128(1):280-288

Lyon, France; and Dallas, Texas From the Department of Plastic, Aesthetic, and Reconstructive Surgery, Edouard Herriot Hospital, and the Department of Plastic Surgery, University of Texas Southwestern Medical Center.

Background: Preservation or reconstruction of the middle nasal vault structure and internal nasal valve after dorsal reduction is challenging. The purpose of this study was to retrospectively analyze a series of 100 consecutive rhinoplasty cases with respect to preservation or restoration of the dorsal nasal lines following component dorsal reduction. A new quantitative mathematical application for subject digital images was performed.

Methods: Medical information and digital images were obtained from 100 consecutive primary rhinoplasty patients from one author (R.J.R.) with University of Texas Southwestern Medical Center Institutional Review Board consent. All postoperative subject digital images were taken at more than 1-year follow-up. Preoperative and postoperative digital images of the dorsal nasal aesthetic lines were analyzed using a software application that quantitated various facial anatomical features compared with landmark measurements unique for each subject (pupil-to-pupil distance). Dorsal line symmetry, nose width, and variation of deformities on each side of the face were determined.

Results: Mean subject dorsal line symmetry was 68 percent preoperatively and 94 percent postoperatively. Only 32.5 percent of dorsal lines were harmonious preoperatively, whereas 97 percent of dorsal lines were harmonious postoperatively. Identification of dorsal lines postoperatively versus preoperatively was similar in 74.6 percent, improved in 15.7 percent, and decreased in 9.7 percent. Nasal width lines were similar in 36 subjects, 21 subjects had wider nasal width lines, and 43 subjects had narrower width lines after surgery.

Conclusions: Component dorsal hump reduction procedures result in reliable and reproducible clinical outcomes. Quantitative assessments provide evidence that improved and harmonious curves of dorsal aesthetic lines are achievable.

Clinical Question/level Of Evidence: Therapeutic, IV.(Figure is included in full-text article.).
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http://dx.doi.org/10.1097/PRS.0b013e318218fc2dDOI Listing
July 2011

Effects of coagulase-negative staphylococci and fibrin on breast capsule formation in a rabbit model.

Aesthet Surg J 2011 May;31(4):420-8

Hospital de Sao Joao, Servico de Cirurgia Plastica, Porto, Portugal.

Background: The etiology and ideal clinical treatment of capsular contracture (CC) remain unresolved. Bacteria, especially coagulase-negative staphylococci, have been previously shown to accelerate the onset of CC. The role of fibrin in capsule formation has also been controversial.

Objective: The authors investigate whether fibrin and coagulase-negative staphylococci (CoNS) modulate the histological, microbiological, and clinical outcomes of breast implant capsule formation in a rabbit model and evaluate contamination during the surgical procedure.

Methods: Thirty-one New Zealand white female rabbits were each implanted with one tissue expander and two breast implants. The rabbits received (1) untreated implants and expanders (control; n = 10), (2) two implants sprayed with 2 mL of fibrin and one expander sprayed with 0.5 mL of fibrin (fibrin; n = 11), or (3) two implants inoculated with 100 µL of a CoNS suspension (10(8)CFU/mL-0.5 density on the McFarland scale) and one expander inoculated with a CoNS suspension of 2.5 × 10(7) CFU/mL (CoNS; n = 10). Pressure/volume curves and histological and microbiological evaluations were performed. Operating room air samples and contact skin samples were collected for microbiological evaluation. The rabbits were euthanized at four weeks.

Results: In the fibrin group, significantly decreased intracapsular pressures, thinner capsules, loose/dense (<25%) connective tissue, and negative/mild angiogenesis were observed. In the CoNS group, increased capsular thicknesses and polymorph-type inflammatory cells were the most common findings. Similar bacteria in capsules, implants, and skin were cultured from all the study groups. One Baker grade IV contracture was observed in an implant infected with Micrococcus spp.

Conclusions: Fibrin was associated with reduced capsule formation in this preclinical animal model, which makes fibrin an attractive potential therapeutic agent in women undergoing breast augmentation procedures. Clinical strategies for preventing bacterial contamination during surgery are crucial, as low pathogenic agents may promote CC.
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http://dx.doi.org/10.1177/1090820X11404400DOI Listing
May 2011

Subject global evaluation and subject satisfaction using injectable poly-L-lactic acid versus human collagen for the correction of nasolabial fold wrinkles.

Plast Reconstr Surg 2011 Apr;127(4):1684-1692

Dallas, Texas; Miami, Coral Gables, and Boca Raton, Fla.; Buffalo Grove, Ill.; Los Angeles and Santa Monica, Calif.; Birmingham, Ala.; New York and White Plains, N.Y.; and Seattle and Spokane, Wash. From the University of Texas Southwestern Medical Center; University of Miami; private practice; University of California, Los Angeles School of Medicine; Clinical Research Specialists, Inc.; the Departments of Dermatology and Ophthalmology, University of Alabama at Birmingham; New York University School of Medicine; Dermatology and Aesthetic Center, Inc.; University of Washington School of Medicine; and Premier Clinical Research.

Background: This is a report of the secondary endpoints, Subject Global Evaluation (overall improvement) and Subject Satisfaction scores, from a study designed to examine the efficacy of injectable poly-L-lactic acid for the correction of nasolabial fold wrinkles over 25 months.

Methods: A randomized, subject-blinded, parallel-group, multicenter clinical study was conducted to compare the effects of injectable poly-L-lactic acid with those of human collagen for the treatment of nasolabial fold wrinkles at 13 months following the last treatment. Injectable poly-L-lactic acid-treated subjects were followed for 25 months.

Results: From month 3 through month 13 following the last treatment, injectable poly-L-lactic acid-treated subjects (n = 116) reported significantly higher Subject Global Evaluation scores compared with human collagen-treated subjects (n = 117; p < 0.001). Overall Subject Global Evaluation scores for injectable poly-L-lactic acid-treated subjects were 99 percent at week 3, 91 percent at month 13, and 81 percent at month 25 (all times following the last treatment). In contrast, for human collagen-treated subjects, overall Subject Global Evaluation scores declined by 84 percent, from 96 percent at week 3 to 15 percent at month 13. Subject Satisfaction scores were significantly different (p < 0.01) between treatment groups beginning week 3 and continuing through month 13. Overall Subject Satisfaction scores were maintained for over 80 percent of injectable poly-l-lactic acid-treated subjects (n = 106) at month 25 after the last treatment.

Conclusions: Treatment of nasolabial fold wrinkles with injectable poly-l-lactic acid resulted in statistically significantly higher Subject Global Evaluation and Subject Satisfaction scores compared with human collagen at 13 months. Injectable poly-l-lactic acid-treated subjects maintained improvements for up to 25 months after treatment.
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http://dx.doi.org/10.1097/PRS.0b013e318208d371DOI Listing
April 2011