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Delivery of Macrophages in a Biomimetic Scaffold Accelerates Diabetic Wound Healing Through Enhanced Angiogenesis
Vol. 221, No. 4S1, October 2015
Scientific Forum Abstracts
S113
Combining CT Angiography Mapping with ComputerAided Design and Manufacturing Planning for Free Fibula Flap Reconstruction of Mandibulectomy Defects Noopur Gangopadhyay, MD, Mark T Villa, MD, FACS, Edward I Chang, MD, Jesse C Selber, MD, FACS, Jun Liu, MD, PhD, Patirck B Garvey, MD, FACS University of Texas MD Anderson Cancer Center, Houston, TX
METHODS: The 2006 to 2013 NSQIP databases were scanned for postoperative ICD-9 codes for prophylactic breast or ovary removal. From this sample, we included female patients whose records contained at least 1 of 7 CPT codes for mastectomy or breast reconstruction, and/or 1 of 5 CPT codes that include ovarian removal. Patient data were analyzed using JMP, with ANOVA used to compare means and Pearson’s chi-square for proportions across the 3 groups.
INTRODUCTION: Surgeons have used computer-aided design and manufacturing (CAD/CAM) for fibula flap reconstruction. We combined CAD/CAM with CT angiography (CTA) to map peroneal artery perforators for the skin island. We hypothesized that CAD/CAM+CTA would decrease operative times and improve patient outcomes.
RESULTS: The inclusion criteria captured 2,527 patients. Of these, 2,248 underwent solely breast procedures, 193 solely gynecologic procedures, and 86 received both simultaneously. There were no significant differences in age, race, or BMI (Table). The combined cases had a longer operative time than independent breast or gynecologic procedures. However, no significant differences in the rates of surgical site infections, urinary tract infections, graft/ prosthesis/flap failure, or length of stay were observed.
METHODS: We retrospectively compared consecutive patients (n¼159) at a single center who underwent mandibulectomy reconstruction with free fibula flaps, for whom CAD/CAM+CTA (n¼38), CTA-only (n¼64), or neither technology (n¼57) were used over a 7-year period (2008 to 2015). We used logistic regression analysis to identify potential associations between patient and reconstructive factors and postoperative outcomes. RESULTS: Patient characteristics were similar between the 3 groups. The number of fibula osteotomies was significantly higher in the CAD/ CAM+CTA group vs both the CTA-only and conventional fibula groups (1.4 vs 1.0 vs 1.0; p¼0.02). Flap ischemia time was significantly shorter in both the CAD/CAM+CTA and CTA-only groups vs the conventional fibula group (80 vs 87 vs 121 minutes; p<0.01), while total operative time was similar between the groups (616 vs 641 vs 646 minutes; p¼0.56). Average lengths of hospital stay were similar, but ICU stay was significantly shorter in the CAD/CAM+CTA and CTA-only groups vs the conventional fibula group (2.1 vs 2.1 vs 7.6 days; p<0.01). Surgical complication rates, including flap failure rates, were similar between the 3 groups (p¼0.49). CONCLUSIONS: Preoperatively combining the use of CAD/CAM and CTA for mandibular reconstruction with free fibula flaps appears to add value by facilitating more complex reconstructions, shorter ischemia times, shorter ICU stays, and improved postoperative outcomes. Combining Prophylactic Oophorectomy with Mastectomy Does Not Adversely Affect Surgical Outcomes: Results from the NSQIP Database Jared Blau, Charlotte Gamble, MD, Rachel A Anolik, MD, Laura Havrilesky, MD, Rachel A Greenup, MD, Scott T Hollenbeck, MD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Mastectomy is often performed for patients with a genetic predisposition toward developing breast cancer. Carriers of the BRCA mutation may also undergo prophylactic oophorectomy to prevent ovarian cancer. Providing both procedures simultaneously reduces the burden of 2 operations and hospitalizations, but it is not clear if combining them poses additional risk. We queried the American College of Surgeons NSQIP database to examine the differences in outcomes between these independent and combined prophylactic cases.
Table. Selected Patient Surgical Outcomes Variable
Demographics
and
30-Day
Breast only Gyn only Combined (n ¼ 2,248) (n ¼ 193) (n ¼ 86) p Value
Age, y Race, white, %
47.3 81.8
48.3 84.4
47.6 90.7
BMI, kg/m2 Operative time, min Length of hospital stay, d Superficial surgical site infection, % Deep surgical site infection, % Urinary tract infection, % Graft/prosthesis/ flap failure, %
27.7
28.0
27.0
0.43 0.29, all races 0.56
237.1
115.2
275.2
<0.0001
2.4
1.1
1.8
0.28
2.5
0.5
0.0
0.07
1.2
0.0
2.3
0.19
0.4
1.0
0.0
0.36
0.6
0.0
0.0
0.42
CONCLUSIONS: Combining mastectomy and/or breast reconstruction with oophorectomy increases operative time but does not negatively affect surgical outcomes or length of stay. The NSQIP data suggest that combining them into a simultaneous procedure does not increase 30-day complications. Delivery of Macrophages in a Biomimetic Scaffold Accelerates Diabetic Wound Healing Through Enhanced Angiogenesis Graham G Walmsley, Michael S Hu, MD, MPH, Dominik Duscher, MD, Michael Januszyk, MD, PhD, Zeshaan N Maan, MB, BS, MRCS, Kshemendra Senarath-Yapa, MD, Ruth Tevlin, MB, BCh, MRCSI, Elizabeth R Zielins, MD, Geoffrey C Gurtner, MD, FACS, Michael T Longaker, MD, MBA, FACS Stanford University, Stanford, CA
S114
Scientific Forum Abstracts
INTRODUCTION: Macrophages play a critical regulatory role during several stages of wound healing, including angiogenesis, reepithelialization, and remodeling. Evidence for the importance of macrophages in these processes comes from experiments demonstrating impaired wound healing in mice after inhibition or knock-out of macrophages. METHODS: A mouse model of splinted excisional wound healing was used for all experiments to better approximate human wound healing. Macrophages were derived from the bone marrow of leptin receptor-deficient (db/db) mice, seeded onto pullulan-collagen hydrogels, and transplanted into 6-mm splinted excisional dorsal wounds in db/db mice. Histologic and microfluidic single-cell gene expression analysis allowed for assessment of survival, localization, and phenotype of transplanted cells. RESULTS: The average time to complete wound healing was 17.4 days in the macrophage group vs 20.5 days in the control group (p<0.01). Microfluidic single-cell and histologic analysis revealed that transplanted db/db macrophages acquired a predominantly M2 “repair” phenotype after 72 hours in the wound environment. Fully healed macrophage-treated wounds expressed CD31 to a significantly greater degree than controls (p<0.01). Scar size and quality were not significantly affected. CONCLUSIONS: The transplantation of macrophages significantly increases the rate of wound healing through enhanced angiogenesis in diabetic mice, with no adverse impact on the quality of repair. These findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases in which wound healing is impaired. Hydrocellular Foam is a Cost-Effective Dressing for Preventing Pressure Ulcers: A Randomized Controlled Study Ihab Saab, MD, Jane F Solomon, RN, Latoya Allen, Aamir Siddiqui, MD, FACS Henry Ford Hospital, Detroit, MI INTRODUCTION: Pressure ulcers add significant morbidity to the surgical patient. In a recent open-label study, we elucidated that hydrocellular foam dressing is effective in preventing pressure ulcers. Building on our initial positive results, we carried out a randomized controlled trial to assess the effectiveness of foam dressing in reducing pressure ulcers in the surgical ICU (SICU). METHODS: Patients admitted to SICU from July to November 2014 were included in the study. The patients were randomized to the control group or to have a gel adhesive hydrocellular foam dressing applied to the sacrum. Patients were followed prospectively until being discharged or transferred from the SICU. Standard care bundles to prevent pressure ulcers were continued. The buttocks and the sacrum were examined daily and the dressing was replaced as needed. RESULTS: A total of 80 patients were included (treatment group, n¼35; control group, n¼45); 35 patients were women.
J Am Coll Surg
Mean age was 62 17.2 years, with a mean Braden score of 15.1. The foam dressing was applied for a mean of 5.71 8.3 days. Six patients developed sacral ulcers in the control group, none in the treatment group (p ¼0.0247). The average treatment cost of a pressure ulcer is $43,000. The mean cost of the hydrocellular dressing per patient stay was $16.8$24.5. CONCLUSIONS: Hydrocellular dressing is a cost effective tool that significantly prevents the development of pressure ulcers. The mechanism of action has not been completely elucidated. Possible reduction in shear, temperature, friction, moisture and pressure play a role in decreasing hospital-acquired pressure ulcers. Hydrogen Sulfide Delays Onset of Acute Rejection in Porcine Vascularized Composite Allotransplantation Model Sharon D Lawson, MD, Lin C Wang, MD, Charles A Fries, Michael R Davis, MD, FACS United States Army Institute for Surgical Research, San Antonio, TX INTRODUCTION: Advances in military medicine have resulted in soldiers surviving battlefield trauma after catastrophic injuries. Reconstructive transplantation, or vascularized composite allotransplantation (VCA), offers a means for superior functional recovery after devastating injuries compared to traditional reconstructive techniques. Here we evaluate the efficacy of hydrogen sulfide (H2S) as a targeted, graft-specific treatment, to mitigate reperfusion injury and delay the onset of acute rejection in a porcine VCA model. Translating these results may reduce dosing requirements for systemic immunosupression, allowing for reduced toxicity and improved applicability of VCA as a reconstructive technique. METHODS: Gracilis myocutaneous flaps were procured from Yorkshire swine and transplanted heterotopically into single swine leucocyte antigen (SLA) mismatched recipients. Group 1 (controls, n¼8) flaps received no treatment before transplantation. Group 2 (experimental, n¼8) flaps received ex-vivo, intra-arterial infusion with H2S solution (1 mL of 11.6-mg/mL solution per 400 g [weight of flap]). Venous perfusate was collected and reperfused for 5 cycles before transplantation. Serum and tissue samples were taken for a 14-day survival period and rejection graded using the Banff scale. Histologic evaluation was blinded. RESULTS: The mean times to grade 1 rejection for group 1 and group 2 were 6.4 days (SD 0.52) and 8.9 days (SD 2.3, p<0.05), respectively. The mean time to grade 4 acute rejection was 10.5 days (SD 2.6) for group 1, and >14 days for group 2. CONCLUSIONS: In the absence of systemic immunosuppression, ameliorating ischemic reperfusion injury with the use of hydrogen sulfide at the time of allotransplantation effectively delays the onset of acute rejection in VCA grafts.
Scientific Forum Abstracts
S113
Combining CT Angiography Mapping with ComputerAided Design and Manufacturing Planning for Free Fibula Flap Reconstruction of Mandibulectomy Defects Noopur Gangopadhyay, MD, Mark T Villa, MD, FACS, Edward I Chang, MD, Jesse C Selber, MD, FACS, Jun Liu, MD, PhD, Patirck B Garvey, MD, FACS University of Texas MD Anderson Cancer Center, Houston, TX
METHODS: The 2006 to 2013 NSQIP databases were scanned for postoperative ICD-9 codes for prophylactic breast or ovary removal. From this sample, we included female patients whose records contained at least 1 of 7 CPT codes for mastectomy or breast reconstruction, and/or 1 of 5 CPT codes that include ovarian removal. Patient data were analyzed using JMP, with ANOVA used to compare means and Pearson’s chi-square for proportions across the 3 groups.
INTRODUCTION: Surgeons have used computer-aided design and manufacturing (CAD/CAM) for fibula flap reconstruction. We combined CAD/CAM with CT angiography (CTA) to map peroneal artery perforators for the skin island. We hypothesized that CAD/CAM+CTA would decrease operative times and improve patient outcomes.
RESULTS: The inclusion criteria captured 2,527 patients. Of these, 2,248 underwent solely breast procedures, 193 solely gynecologic procedures, and 86 received both simultaneously. There were no significant differences in age, race, or BMI (Table). The combined cases had a longer operative time than independent breast or gynecologic procedures. However, no significant differences in the rates of surgical site infections, urinary tract infections, graft/ prosthesis/flap failure, or length of stay were observed.
METHODS: We retrospectively compared consecutive patients (n¼159) at a single center who underwent mandibulectomy reconstruction with free fibula flaps, for whom CAD/CAM+CTA (n¼38), CTA-only (n¼64), or neither technology (n¼57) were used over a 7-year period (2008 to 2015). We used logistic regression analysis to identify potential associations between patient and reconstructive factors and postoperative outcomes. RESULTS: Patient characteristics were similar between the 3 groups. The number of fibula osteotomies was significantly higher in the CAD/ CAM+CTA group vs both the CTA-only and conventional fibula groups (1.4 vs 1.0 vs 1.0; p¼0.02). Flap ischemia time was significantly shorter in both the CAD/CAM+CTA and CTA-only groups vs the conventional fibula group (80 vs 87 vs 121 minutes; p<0.01), while total operative time was similar between the groups (616 vs 641 vs 646 minutes; p¼0.56). Average lengths of hospital stay were similar, but ICU stay was significantly shorter in the CAD/CAM+CTA and CTA-only groups vs the conventional fibula group (2.1 vs 2.1 vs 7.6 days; p<0.01). Surgical complication rates, including flap failure rates, were similar between the 3 groups (p¼0.49). CONCLUSIONS: Preoperatively combining the use of CAD/CAM and CTA for mandibular reconstruction with free fibula flaps appears to add value by facilitating more complex reconstructions, shorter ischemia times, shorter ICU stays, and improved postoperative outcomes. Combining Prophylactic Oophorectomy with Mastectomy Does Not Adversely Affect Surgical Outcomes: Results from the NSQIP Database Jared Blau, Charlotte Gamble, MD, Rachel A Anolik, MD, Laura Havrilesky, MD, Rachel A Greenup, MD, Scott T Hollenbeck, MD, FACS Duke University Medical Center, Durham, NC INTRODUCTION: Mastectomy is often performed for patients with a genetic predisposition toward developing breast cancer. Carriers of the BRCA mutation may also undergo prophylactic oophorectomy to prevent ovarian cancer. Providing both procedures simultaneously reduces the burden of 2 operations and hospitalizations, but it is not clear if combining them poses additional risk. We queried the American College of Surgeons NSQIP database to examine the differences in outcomes between these independent and combined prophylactic cases.
Table. Selected Patient Surgical Outcomes Variable
Demographics
and
30-Day
Breast only Gyn only Combined (n ¼ 2,248) (n ¼ 193) (n ¼ 86) p Value
Age, y Race, white, %
47.3 81.8
48.3 84.4
47.6 90.7
BMI, kg/m2 Operative time, min Length of hospital stay, d Superficial surgical site infection, % Deep surgical site infection, % Urinary tract infection, % Graft/prosthesis/ flap failure, %
27.7
28.0
27.0
0.43 0.29, all races 0.56
237.1
115.2
275.2
<0.0001
2.4
1.1
1.8
0.28
2.5
0.5
0.0
0.07
1.2
0.0
2.3
0.19
0.4
1.0
0.0
0.36
0.6
0.0
0.0
0.42
CONCLUSIONS: Combining mastectomy and/or breast reconstruction with oophorectomy increases operative time but does not negatively affect surgical outcomes or length of stay. The NSQIP data suggest that combining them into a simultaneous procedure does not increase 30-day complications. Delivery of Macrophages in a Biomimetic Scaffold Accelerates Diabetic Wound Healing Through Enhanced Angiogenesis Graham G Walmsley, Michael S Hu, MD, MPH, Dominik Duscher, MD, Michael Januszyk, MD, PhD, Zeshaan N Maan, MB, BS, MRCS, Kshemendra Senarath-Yapa, MD, Ruth Tevlin, MB, BCh, MRCSI, Elizabeth R Zielins, MD, Geoffrey C Gurtner, MD, FACS, Michael T Longaker, MD, MBA, FACS Stanford University, Stanford, CA
S114
Scientific Forum Abstracts
INTRODUCTION: Macrophages play a critical regulatory role during several stages of wound healing, including angiogenesis, reepithelialization, and remodeling. Evidence for the importance of macrophages in these processes comes from experiments demonstrating impaired wound healing in mice after inhibition or knock-out of macrophages. METHODS: A mouse model of splinted excisional wound healing was used for all experiments to better approximate human wound healing. Macrophages were derived from the bone marrow of leptin receptor-deficient (db/db) mice, seeded onto pullulan-collagen hydrogels, and transplanted into 6-mm splinted excisional dorsal wounds in db/db mice. Histologic and microfluidic single-cell gene expression analysis allowed for assessment of survival, localization, and phenotype of transplanted cells. RESULTS: The average time to complete wound healing was 17.4 days in the macrophage group vs 20.5 days in the control group (p<0.01). Microfluidic single-cell and histologic analysis revealed that transplanted db/db macrophages acquired a predominantly M2 “repair” phenotype after 72 hours in the wound environment. Fully healed macrophage-treated wounds expressed CD31 to a significantly greater degree than controls (p<0.01). Scar size and quality were not significantly affected. CONCLUSIONS: The transplantation of macrophages significantly increases the rate of wound healing through enhanced angiogenesis in diabetic mice, with no adverse impact on the quality of repair. These findings hold promise for translational medicine aimed at accelerating wound healing across a broad spectrum of diseases in which wound healing is impaired. Hydrocellular Foam is a Cost-Effective Dressing for Preventing Pressure Ulcers: A Randomized Controlled Study Ihab Saab, MD, Jane F Solomon, RN, Latoya Allen, Aamir Siddiqui, MD, FACS Henry Ford Hospital, Detroit, MI INTRODUCTION: Pressure ulcers add significant morbidity to the surgical patient. In a recent open-label study, we elucidated that hydrocellular foam dressing is effective in preventing pressure ulcers. Building on our initial positive results, we carried out a randomized controlled trial to assess the effectiveness of foam dressing in reducing pressure ulcers in the surgical ICU (SICU). METHODS: Patients admitted to SICU from July to November 2014 were included in the study. The patients were randomized to the control group or to have a gel adhesive hydrocellular foam dressing applied to the sacrum. Patients were followed prospectively until being discharged or transferred from the SICU. Standard care bundles to prevent pressure ulcers were continued. The buttocks and the sacrum were examined daily and the dressing was replaced as needed. RESULTS: A total of 80 patients were included (treatment group, n¼35; control group, n¼45); 35 patients were women.
J Am Coll Surg
Mean age was 62 17.2 years, with a mean Braden score of 15.1. The foam dressing was applied for a mean of 5.71 8.3 days. Six patients developed sacral ulcers in the control group, none in the treatment group (p ¼0.0247). The average treatment cost of a pressure ulcer is $43,000. The mean cost of the hydrocellular dressing per patient stay was $16.8$24.5. CONCLUSIONS: Hydrocellular dressing is a cost effective tool that significantly prevents the development of pressure ulcers. The mechanism of action has not been completely elucidated. Possible reduction in shear, temperature, friction, moisture and pressure play a role in decreasing hospital-acquired pressure ulcers. Hydrogen Sulfide Delays Onset of Acute Rejection in Porcine Vascularized Composite Allotransplantation Model Sharon D Lawson, MD, Lin C Wang, MD, Charles A Fries, Michael R Davis, MD, FACS United States Army Institute for Surgical Research, San Antonio, TX INTRODUCTION: Advances in military medicine have resulted in soldiers surviving battlefield trauma after catastrophic injuries. Reconstructive transplantation, or vascularized composite allotransplantation (VCA), offers a means for superior functional recovery after devastating injuries compared to traditional reconstructive techniques. Here we evaluate the efficacy of hydrogen sulfide (H2S) as a targeted, graft-specific treatment, to mitigate reperfusion injury and delay the onset of acute rejection in a porcine VCA model. Translating these results may reduce dosing requirements for systemic immunosupression, allowing for reduced toxicity and improved applicability of VCA as a reconstructive technique. METHODS: Gracilis myocutaneous flaps were procured from Yorkshire swine and transplanted heterotopically into single swine leucocyte antigen (SLA) mismatched recipients. Group 1 (controls, n¼8) flaps received no treatment before transplantation. Group 2 (experimental, n¼8) flaps received ex-vivo, intra-arterial infusion with H2S solution (1 mL of 11.6-mg/mL solution per 400 g [weight of flap]). Venous perfusate was collected and reperfused for 5 cycles before transplantation. Serum and tissue samples were taken for a 14-day survival period and rejection graded using the Banff scale. Histologic evaluation was blinded. RESULTS: The mean times to grade 1 rejection for group 1 and group 2 were 6.4 days (SD 0.52) and 8.9 days (SD 2.3, p<0.05), respectively. The mean time to grade 4 acute rejection was 10.5 days (SD 2.6) for group 1, and >14 days for group 2. CONCLUSIONS: In the absence of systemic immunosuppression, ameliorating ischemic reperfusion injury with the use of hydrogen sulfide at the time of allotransplantation effectively delays the onset of acute rejection in VCA grafts.