Faculty Bibliography

BACKGROUND: The pectoralis major muscle flap is a versatile reconstructive option for deep sternal wound infections (DSWI). The timing and surgical technique of bilateral pectoralis major muscle advancement flaps versus unilateral pectoralis major muscle turnover and unilateral pectoralis major muscle advancement flap on patient outcomes remain to be elucidated. The purpose of this investigation was to compare timing, immediate versus delayed reconstruction, and the surgical technique in patients with deep sternal wounds infections on patient outcomes. METHODS: A retrospective review of patients who underwent sternal reconstruction with pectoralis major muscle was conducted. Patients diagnosed with DSWI after undergoing cardiac surgery were included for analysis. Patients were divided by flap timing and flap type for analyses. Bivariate tests were performed to compare patient clinical characteristics. Outcomes of interest were rates of postoperative complications, same admission mortality, reoperation, readmission, operating room time, and length of stay. RESULTS: = 0.019). CONCLUSION/CONCLUSIONS: Patients who underwent pectoralis major muscle advancement flaps had lower incidence of tissue necrosis. Furthermore, the timing of immediate sternal reconstruction was associated with a decreased hospital length of stay.

INTRODUCTION/BACKGROUND:The number of patients who may benefit from evaluation for face transplantation in the United States (US) remains largely unknown. The goal of our study was to better delineate the pool of patients who might benefit from face transplant evaluation based on the characteristics and mechanisms of injury of previously reported face transplant recipients. METHODS:The authors utilized data from the National Electronic Injury Surveillance System-All Injury Program in this study. The US Census Bureau data were used for population estimates. Inclusion and exclusion criteria were determined based on the characteristics of face transplant recipients to date, and the mechanisms of injury they sustained ultimately necessitating face transplantation. Statistical significance was reached if P <0.05. RESULTS:The estimated annual incidence of preventable craniofacial injuries from firearms (44,266-58,299; 31.7% increase), burns (5712-19,433; 240.2% increase), and animal attacks (5355-14,666; 173.9% increase) increased from 2005 to 2014, whereas the estimated annual incidence of craniofacial injuries from machinery (3927-2933; 25.3% decrease) decreased between 2005 and 2014. The authors estimate the annual incidence rate to fall between 32.1 per 100,000 and 58.1 per 100,000 among individuals aged 20 to 64 in the US. CONCLUSION/CONCLUSIONS:In this study, the authors estimate the annual incidence rate of individuals aged 20 to 64 in the US who may benefit from face transplant evaluation and believe that this quantification has the potential to initiate actionable discussions regarding geographical and financial factors affecting access to care in this patient population.

BACKGROUND:Gustilo type IIIC open tibia fractures are characterized by an ischemic limb requiring immediate arterial repair. In this patient population, the decision between primary amputation and limb salvage can be challenging. This study aims to evaluate the reconstructive outcomes of patients with Gustilo type IIIC injuries. METHODS:A single-center retrospective review of 806 lower extremity free flaps from 1976 to 2016 was performed. Flap loss and salvage rates for patients with Gustilo type IIIC injuries were determined. To determine the utility of performing salvage in this group, outcomes of the IIIC reconstructions were compared to those of similar patients with Gustilo I type IIB injuries with only a single patent vessel. RESULTS:A total of 32 patients with Gustilo type IIIC injuries underwent reconstruction after traumatic injury. Ten patients (31.3 percent) experienced a perioperative complication, including seven unplanned returns to the operating room (21.9 percent), three partial flap losses (9.4 percent), and five complete flap losses (15.6 percent). When type IIIC injuries were compared with single-vessel Gustilo type IIIB injuries, no statistically significant differences were noted with respect to major perioperative complications (p = 0.527), unplanned return to the operating room (p = 0.06), partial flap loss (p = 0.209), complete flap loss (p = 0.596), or salvage rate (p = 0.368). Although this result was not statistically significant, Gustilo type IIIC injuries trended toward lower take-back rates and higher salvage rates compared with single-vessel Gustilo type IIIB injuries. CONCLUSION/CONCLUSIONS:Patients with Gustilo type IIIC open tibia fractures should be considered candidates for limb salvage, as flap loss and reconstruction of these injuries are comparable to those of the routinely reconstructed single-vessel runoff type IIIB injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, IV.

BACKGROUND: Venous outflow problems are the most common reasons for perioperative flap complications. Size mismatch in venous anastomoses poses a theoretical problem by promoting turbulent flow and subsequent thrombus formation. The purpose of this study was to determine if increased vein size mismatch is predictive of flap failure. METHODS: Retrospective review of our institutional flap registry from 1979 to 2016 identified 410 free flaps performed for reconstruction of lower extremity trauma. Patient demographics, flap characteristics, and flap outcomes were examined. Venous size mismatch was defined as a difference in size ≥ 1 mm between the recipient vein and flap vein. RESULTS: = 0.045; odds ratio: 2.58). CONCLUSION/CONCLUSIONS: Flaps with vein size mismatch ≥ 1 mm demonstrated increased flap complication rates in the setting of end-to-end venous anastomoses. End-to-side anastomosis was preferentially used in vein size mismatch and carried a higher risk of flap failure. Our results support using veins of similar size for anastomosis whenever feasible to protect against flap complications.

BACKGROUND:Development of diabetic foot ulcers is a common complication of diabetes. Standard-of-care (SOC) therapy alone is often not sufficient to heal these wounds, resulting in application of adjuvant wound therapies including biologic skin substitutes. Although a variety of products exist, it has been difficult to formulate conclusions on their clinical efficacy. We therefore performed a systematic review and meta-analysis on the efficacy of healing diabetic foot ulcers with biologic skin substitutes. METHODS:A systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Four electronic databases (PubMed/MEDLINE, EMBASE [Ovid], Cochrane CENTRAL [Ovid], and Web of Science) were searched from inception through February 27, 2019. Searches included keywords and subject headings pertaining to 3 main concepts: biologic skin substitutes, wound healing, and diabetic foot ulcers. Cochrane randomized controlled trial filters were used to narrow results. Data were extracted from 54 included articles, and risk-of-bias assessments were conducted by 2 independent reviewers. The primary objective was to calculate a pooled risk ratio for the proportion of wounds completely closed by 12 weeks. Secondary objectives included a pooled risk ratio for the proportion of wounds completely closed by 6 weeks and mean time to healing. RESULTS:Twenty-five studies were identified that assessed the proportion of complete wound closure by 12 weeks. We found that wounds treated with biologic dressings were 1.67 times more likely to heal by 12 weeks than those treated with SOC dressings (P < 0.00001). Five studies assessed the proportion of complete wound closure by 6 weeks. Wounds treated with biologic dressings were 2.81 times more likely to heal by 6 weeks than those treated with SOC dressings (P = 0.0001). Descriptively, 29 of 31 studies that assessed time to healing favored biologic dressings over SOC dressings. CONCLUSIONS:This systematic review provides supporting evidence that biologic skin substitutes are more effective than SOC dressings at healing diabetic foot ulcers by 12 weeks. Future studies must address the relative benefits of different skin substitutes as well as the long-term implications of these products and their financial considerations.

Large defects of the craniofacial skeleton can be exceedingly difficult to reconstruct since autologous bone grafts are limited by donor site morbidity and alloplastic implants have low biocompatibility. Bone morphogenetic proteins (BMPs) in craniofacial reconstruction have been used with mixed outcomes and complication concerns; however, results for specific indications have been promising.In alveolar clefts, cranial vault defects, mandibular defects, and rare Tessier craniofacial clefts, BMP-2 impregnated in collagen matrix was looked at as an alternative therapy for challenging cases. In cases where structural support was required, BMP-2 was used as part of a construct with bio-resorbable plates. Demineralized bone was added in certain cases.The authors described specific indications, detailed surgical techniques, and a review of the current literature regarding the use of BMP-2 in craniofacial reconstruction. BMP-2 is a viable option for craniofacial reconstruction to decrease donor-site morbidity or when alternatives are contraindicated. It is not recommended for routine use or in the oncologic setting but should currently be reserved as an alternative therapy for complex cases with limited options.Bone morphogenetic proteins are a promising, emerging option for complex craniofacial reconstruction. Future directions of BMP-2 therapies will become apparent as data from prospective randomized trials emerges.

BACKGROUND:Human monoclonal antibodies that potently and broadly neutralise HIV-1 are under development to prevent and treat HIV-1 infection. In this phase 1 clinical trial we aimed to determine the safety, tolerability, and pharmacokinetic profile of the broadly neutralising monoclonal antibody VRC07-523LS, an engineered variant of VRC01 that targets the CD4 binding site of the HIV-1 envelope protein. METHODS:This phase 1, open-label, dose-escalation clinical trial was done at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Individuals were recruited from the greater Washington, DC, area by IRB-approved written and electronic media. We enrolled healthy, HIV-1-negative adults aged 18-50 years. Inclusion criteria were good general health, measured through clinical laboratory tests, medical history, and physical examination. Participants self-selected into one of seven open groups during enrolment without randomisation. Four groups received a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07-523LS, and one group received a single 5 mg/kg subcutaneous dose. Two groups received three doses of either 20 mg/kg intravenous VRC07-523LS, or 5 mg/kg subcutaneous VRC07-523LS at 12-week intervals. The primary outcome was the safety and tolerability of VRC07-523LS, assessed by dose, route, and number of administrations. This study is registered with ClinicalTrials.gov, NCT03015181. FINDINGS/RESULTS:Between Feb 21, 2017, and September 13, 2017, we enrolled 26 participants, including 11 (42%) men and 15 (58%) women. Two (8%) participants withdrew from the study early: one participant in group 1 enrolled in the study but never received VRC07-523LS, and one participant in group 6 chose to withdraw after a single administration. One (4%) participant in group 7 received only one of the three scheduled administrations. 17 participants received intravenous administrations and 8 participants received subcutaneous administrations. VRC07-523LS was safe and well tolerated, we observed no serious adverse events or dose-limiting toxic effects. All reported local and systemic reactogenicity was mild to moderate in severity. The most commonly reported symptoms following intravenous administration were malaise or myalgia in three (18%) participants and headache or chills in two (12%) participants. The most commonly reported symptoms following subcutaneous administration were pain and tenderness in four participants (50%) and malaise or headache in three (38%) participants. INTERPRETATION/CONCLUSIONS:Safe and well tolerated, VRC07-523LS is a strong and practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. The results from this trial also indicate that an HIV-1 broadly neutralising monoclonal antibody engineered for improved pharmacokinetic and neutralisation properties can be safe for clinical use. FUNDING/BACKGROUND:National Institutes of Health.

Uterus transplantation is an emerging technology adding to the arsenal of treatments for infertility; specifically the only available treatment for uterine factor infertility. Ethical investigations concerning risks to uteri donors and transplant recipients have been discussed in the literature. However, missing from the discourse is the potential of uterus transplantation in other groups of genetically XY women who experience uterine factor infertility. There have been philosophical inquiries concerning uterus transplantation in genetically XY women, which includes transgender women and women with complete androgen insufficiency syndrome. We discuss the potential medical steps necessary and associated risks for uterus transplantation in genetically XY women. Presently, the medical technology does not exist to make uterus transplantation a safe and effective option for genetically XY women, however this group should not be summarily excluded from participation in trials. Laboratory research is needed to better understand and reduce medical risk and widen the field to all women who face uterine factor infertility.

BACKGROUND:Despite the medical necessity, legislative mandates, and economic benefits of gender-affirming surgery, access to treatment remains limited. The World Professional Association for Transgender Health (WPATH) has proposed guidelines for transition-related surgery in conjunction with criteria to delineate medical necessity. The authors assessed insurance coverage of "top" gender-affirming surgery and evaluated the differences between insurance policy criteria and WPATH recommendations. METHODS:The authors conducted a cross-sectional analysis of insurance policies for coverage of top gender-affirming surgery. Insurance companies were selected based on their state enrollment data and market share. A Web-based search and individual telephone interviews were conducted to identify the policy. Medical necessity criteria were abstracted from publicly available policies. RESULTS:Of the 57 insurers evaluated, bilateral mastectomy (transmasculine) was covered by significantly more insurers than breast augmentation (transfeminine) (96 percent versus 68 percent; p < 0.0001). Only 4 percent of companies used WPATH-consistent criteria. No criterion was universally required by insurers. Additional prerequisites for coverage that extended beyond WPATH guidelines for top surgery were continuous living in congruent gender role, two referring mental health professionals, and hormone therapy before surgery. Hormone therapy was required in a significantly higher proportion of transfeminine policies compared with transmasculine policies (90 percent versus 21 percent; p < 0.0001). CONCLUSIONS:In addition to the marked intercompany variation in criteria for insurance coverage that often deviated from WPATH recommendations, there are health care insurers who categorically deny access to top gender-affirming surgery. A greater evidence base is needed to provide further support for the medical necessity criteria in current use.