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Background: Hand form and function play a vital role in daily living, and even minor trauma can significantly impair quality of life. There is a current paucity of data regarding hand burn patient and injury characteristics, particularly in urban areas in the United States. As the field of hand surgery expands, a demographic understanding of patients with severe injury potentially requiring surgical management is imperative. The aim of this study was to define the epidemiological characteristics of burn injuries involving the hand that were admitted to a large New York City burn center., Methods: A retrospective review of the electronic health record was conducted to identify all patients admitted to our burn center with burn injury involving the hand from August 2020 to December 2023. Patient demographics, injury etiology and characteristics, and hospital course details were recorded and analyzed., Results: We identified 96 admitted patients with 140 hand burn injuries, with a patient median age of 38 years. Female patients presented to the hospital significantly later after initial injury than male patients and were more likely to suffer from flame-related injury. The median length of stay for initial admission was 17.5 days, with longer length of stay associated with hypertension comorbidity. Patients experiencing homelessness demonstrated higher rates of psychiatric disorder, substance use, and current smoking. Length of follow-up was positively correlated with estimated household income. Compared to the general city population, the patient cohort was made up of a lower percentage of "White alone" and "Asian alone" race categories and higher percentage of persons experiencing homelessness., Conclusions: We report the clinical and social characteristics of burn patients with hand involvement admitted to a large urban burn center. Hand burn injuries have distinct risk factors and morbidity implications, and consideration for higher-risk groups is imperative for optimal prevention, acute management, and long-term support., Competing Interests: Conflicts of interest and sources of funding: A.J. is a consultant for Integra LifeSciences Corporation. All other authors have no conflicts of interest. The authors received no financial support for this article's research, authorship, and publication., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Authors have speculated that vascularized composite allotransplantation (VCA) recipients may require greater maintenance immunosuppression than solid organ transplant (SOT) recipients due to the higher antigenicity of skin. However, detailed comparisons of VCA and SOT immunosuppression regimens have been limited., Methods: Hand and face VCA recipient immunosuppression data were collected through a systematic literature review. Kidney recipient data were obtained through a retrospective chart review of the authors' institution. Prednisone and mycophenolate mofetil (MMF) doses were compared between VCA and kidney recipients at predefined follow-up intervals (<1, 1-5, and >5 y). Tacrolimus target trough levels (TTTL) were compared at follow-up intervals of 1-5 and >5 y, and stratified into our institution's kidney transplant risk-based target ranges (4-6 ng/mL, 6-8 ng/mL) or higher (>8 ng/mL)., Results: Immunosuppression data were available for 57 VCA and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. VCA recipient mean MMF dose was significantly greater at <1-y (1.71 ± 0.58 versus 1.16 ± 0.55 gm/d; P = 0.01). For VCA recipients, there was a significant difference (P = 0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/mL, 6-8 ng/mL, and >8 ng/mL) between 1 and 5 y (24.0%, 20.0%, 56.0%, respectively) and >5 y (28.6%, 42.9%, 28.6%)., Conclusions: At longer follow-up, VCA and kidney recipients receive comparable MMF/prednisone doses, and most VCA recipients are treated with TTTL similar to kidney recipients. Further research may improve our understanding of VCA's complex risk/benefit ratio, and enhance informed consent., (Copyright © 2020. Published by Elsevier Inc.)

Background: Gender-affirming surgery is becoming increasingly more common. Procedures including chest masculinization, breast augmentation, vaginoplasty, metoidioplasty, and phalloplasty routinely generate discarded tissue. The incidence of finding an occult malignancy or premalignant lesion in specimens from gender-affirming surgery is unknown. The authors therefore conducted a retrospective review of all transgender patients at their institution who underwent gender-affirming surgery to determine the incidence of precancerous and malignant lesions found incidentally., Methods: A retrospective review of transgender patients who underwent gender-affirming surgery at the authors' institution between 2017 and 2018 performed by a single plastic surgeon and a single reconstructive urologic surgeon was conducted. Only transgender patients who underwent gender-affirming surgery that led to routine pathologic review of discarded tissue (mastectomy, vaginoplasty, vaginectomy as part of phalloplasty) were included. Charts were reviewed and patient demographics, duration of hormonal therapy, medical comorbidities, genetic risk factors for cancer, medications (including steroids or other immunosuppressants), pathology reports, and cancer management were recorded., Results: Between 2017 and 2018, 295 transgender patients underwent gender-affirming surgery that generated discarded tissue sent for pathologic evaluation. During this period, 193 bilateral mastectomies, 94 vaginoplasties with orchiectomies, and eight vaginectomies were performed; 6.4 percent of all patients had an atypical lesion found on routine pathologic evaluation., Conclusions: Gender-affirming surgery is increasingly more common given the increase in access to care. The authors' review of routine pathologic specimens generated from gender-affirming surgery yielded a 6.4 percent rate of finding atypical lesions requiring further evaluation. The authors advocate that all specimens be sent for pathologic evaluation., (Copyright © 2020 by the American Society of Plastic Surgeons.)

The "Wide Awake Local Anesthesia No Tourniquet" (WALANT) technique is gaining popularity in hand surgery owing to its benefits of reduced cost, shorter hospital stay, improved safety, and the ability to perform active intraoperative examinations. The aim of this study is to analyze the cost savings and efficiency of performing A1 pulley release for treatment of trigger finger using the WALANT technique in a major city hospital procedure room (PR) as compared with the standard tourniquet, operating room (OR) approach., Methods: Patients who underwent trigger finger release between 2012 and 2017 were identified. Demographic and procedural information were obtained. Patients were followed for an average of 82 and 242 days in the PR and OR groups, respectively., Results: Thirty-nine PR and 37 OR patients were identified. Case length and turnover time were shorter in the PR group [21.4 ± 7 versus 23.5 ± 14.3 min ( P = 0.942) and 31.1 ± 11.1 and 65.3 ± 17.7 min ( P < 0.001), respectively). The cost of the instrument tray utilized was calculated as $3,304.25 in the main OR and $993.79 in the PR. Cost per minute for all personal services in the OR was calculated to be $44/min, a cost that was virtually absent in the PR. Complication rates did not differ between both groups., Conclusion: Performing A1 pulley release for treatment of trigger finger using the WALANT technique is both cost effective and time efficient compared to performing the same procedure in the main OR of a major city public hospital., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: 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: 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.

Introduction: Online resources have become a major source of medical information for the general public. To date, there has not been an assessment of patient-oriented online resources for face and upper extremity transplantation candidates and patients. The goal of this study is to perform a comprehensive assessment of these resources., Methods: Our analysis relied on 2 dimensions: comprehensiveness and readability. Comprehensiveness was evaluated using 14 predetermined variables. Readability was evaluated using 8 different readability scales through the Readability Studio Professional Edition Software (Oleander Software, Ltd, Vandalia, Ohio). Data were also collected from solid organ transplantation (SOT), specifically kidney and liver, programs for comparison., Results: Face and upper extremity transplantation programs were significantly more likely to list exclusion criteria (73.9% vs 41.2%; P = 0.02), the need for life-long immunosuppression (87.0% vs 58.8%; P = 0.02), and benefits of transplantation (91.3% vs 61.8%; P = 0.01) compared with SOT programs. The average readability level of online resources by all face and upper extremity transplantation programs exceeded the sixth grade reading level recommended by the National Institutes of Health and the American Medical Association. The average reading grade level of online resources by these programs was also significantly higher than those of SOT with both exceeding the recommended reading level (13.95 ± 1.55 vs 12.60 ± 1.65; P = 0.003)., Conclusions: Future efforts in face and upper extremity transplantation should be directed toward developing standardized, comprehensive, and intelligible resources with high-quality content and simple language.

Purpose: Penile inversion vaginoplasty is the most common procedure for genital reconstruction in transwomen. While penile inversion vaginoplasty usually provides an excellent aesthetic result, the technique may be complicated by vaginal stenosis and inadequate depth, especially in transwomen with limited penile and scrotal tissue. We describe a technique of using peritoneal flaps to augment the neovaginal apex and canal in penile inversion vaginoplasty for transwomen., Materials and Methods: Between 2017 and 2018 we identified 41 transwomen who underwent primary penile inversion and peritoneal flap vaginoplasty. Two approximately 6 cm wide by 8 cm long peritoneal flaps were raised from the anterior aspect of the rectum and the sigmoid colon, and the posterior aspect of the bladder to create the apex of the neovagina., Results: Average ± SD age of the 41 patients was 34 ± 14 years. Average procedure duration was 262 ± 35 minutes and average length of stay was 5 days. Average followup was 114 ± 79 days. At the most recent followup vaginal depth and width were measured to be 14.2 ± 0.7 and 3.6 ± 0.2 cm, respectively. The peritoneal flap added an additional 5 cm of depth beyond the length of the skin graft, forming the vaginal canal in patients with limited scrotal skin., Conclusions: Penile inversion vaginoplasty remains the gold standard for primary genital reconstruction in transwomen. Peritoneal flaps provide an alternative technique for increased neovaginal depth, creating a well vascularized apex with acceptable anticipated complications.

Background: The Gustilo classification serves as a proxy for injury severity, but recent data suggest rising complications with decreasing arterial runoff. This study aims to compare different microsurgical anastomosis options based on the number of patent vessels in the lower extremity., Methods: A single-center retrospective review of 806 lower extremity free flaps performed from 1976 to 2016 was performed. Patients with Gustilo type IIIB injuries were grouped based on the number of patent vessels in the leg (three, two, or one). Patients were compared based on the type of anastomosis performed, evaluating for perioperative complications and flap failures., Results: Perioperative complications occurred in 111 flaps (27 percent): 71 take-backs (17 percent), 45 partial losses (11 percent), and 37 complete losses (9 percent). Among patients with three-vessel runoff (61.8 percent), there was no difference in take-backs or flap loss between those with end-to-end versus end-to-side anastomoses. In 68 patients (18.7 percent) with two-vessel runoff, no difference between take-backs or flap loss was noted when comparing any anastomosis (i.e., end-to-end into an injured vessel, end-to-end into an uninjured vessel, or end-to-side into an uninjured vessel), although vein grafts were required more often in the end-to-side groups (p < 0.01). Finally, in 39 patients (10.7 percent) with single-vessel runoff, no difference was seen between end-to-end anastomosis into an injured vessel or end-to-side anastomosis into an uninjured vessel in terms of take-backs or flap loss., Conclusion: Higher rates of flap failure correlated with decreasing numbers of patent vessels in the leg, but neither type of microvascular anastomosis nor vessel selection demonstrated any impact on reconstructive outcomes., Clinical Question/level of Evidence: Therapeutic, III.

Background:  Microvascular reconstruction of the lower extremity has the highest reported complication and flap failure rates of any anatomical region. Despite widespread adoption of the mechanical anastomotic venous coupler and encouraging results in other anatomical regions, there are limited reports examining its use in the lower extremity. This study compares outcomes between coupled and hand-sewn venous anastomoses in traumatic lower extremity reconstruction., Methods:  Retrospective review of our institutional flap registry from 1979 to 2016 identified soft tissue free flaps performed for the reconstruction of Gustilo type IIIB/IIIC open tibial fractures. Patient demographics, flap characteristics, use of a venous anastomotic coupler, and perioperative outcomes were examined. Analysis was performed using chi-square and Student's t -tests., Results:  A total of 361 patients received a microvascular free flap for coverage of a Gustilo type IIIB or IIIC tibial fracture following traumatic injury. After excluding cases that lacked adequate information on coupler use, 358 free flaps were included in the study. There were 72 (20%) free flaps performed using a venous coupler and 286 (80%) performed with hand-sewn venous anastomoses. There were comparable rates of major complications (22.2 vs. 26.1%; p  = 0.522), total flap failure (6.5%, vs. 10.2%; p  = 0.362), and partial flap failure (9.7 vs. 12.2%; p  = 0.579) between venous coupler and hand-sewn anastomoses, respectively. Furthermore, use of the venous coupler was not associated with increased rates of operative take backs (22.8 vs. 23.0%; p  = 0.974). However, reconstructions performed using a venous coupler were significantly more likely to have a second venous anastomosis performed (37.5 vs. 21.3%; p  = 0.004)., Conclusion:  Complication and flap failure rates were similar between reconstructions performed with a venous coupler and those performed with hand-sewn venous anastomoses. These findings suggest that use of the venous anastomotic coupler is safe and effective in lower extremity reconstruction, with comparable outcomes to conventional sutured anastomoses., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: The dependent nature of the lower extremity predisposes to venous congestion, especially following significant trauma. The benefit of a second venous anastomosis, however, remains unclear in lower extremity trauma free flap reconstruction. This study investigated the effect of an additional venous anastomosis on flap outcomes in lower extremity trauma reconstruction., Methods: Retrospective review between 1979 and 2016 identified 361 soft tissue flaps performed for Gustilo IIIB/C coverage meeting inclusion criteria. Muscle flaps were performed in 287 cases (79.9%) and fasciocutaneous flaps in 72 cases (20.1%). Single-vein anastomosis was performed in 76% of cases and dual-vein anastmoses in 24% of cases. Patient demographics, flap characteristics, and outcomes were examined., Results: Fasciocutaneous flaps were more likely to have two veins performed (P < .001). Complications occurred in 143 flaps (39.8%): 45 take-backs (12.4%), 37 partial losses (10.3%), 31 complete losses (8.6%). Compared to single-vein flaps, two veins reduced major complications (P = .005), partial flap failures (P = .008), and any flap failure (P = .018). Multivariable regression analysis demonstrated two veins to be protective against complications (RR = 2.58, P = .009). Subset regression analysis by flap type demonstrated an even more significant reduction in complications among muscle flaps (RR = 3.92, P = .005). Additionally, a >1 mm vein size mismatch was predictive of total flap failure (RR = 3.02, P = .038)., Conclusion: Lower extremity trauma free flaps with two venous anastomoses demonstrated a fourfold reduction in complication rates compared to single-vein flaps. Additionally, venous size mismatch >1 mm was an independent predictor of total flap failure, suggesting beneficial effects of both two-vein outflow and matched vessel diameter., (© 2017 Wiley Periodicals, Inc.)

The unique anatomical characteristics of the forearm region make it especially popular as a free flap donor site for craniofacial soft-tissue reconstruction. The free ulnar forearm flap is less hirsute and allows for better concealment of donor site scar as compared with its radial counterpart. Despite these factors, the free radial forearm flap remains more popular among reconstructive surgeons. Through the presented case series, we hope to emphasize the versatile nature of the free ulnar forearm flap in addressing various craniofacial soft-tissue defects. Following institutional review board approval, a retrospective review of the senior authors' clinical experience performing microvascular free ulnar forearm flap reconstruction of craniofacial soft-tissue defects was performed. A total of 10 patients were identified through our review. Soft-tissue defect locations included lower eyelid (n = 2), tongue and floor of mouth (n = 2), lower lip (n = 2), palatopharyngeal area (n = 1), nose (n = 1), and palate (n = 1). Trauma was the most common defect etiology (n = 5), followed by malignancy (n = 4), and iatrogenic injury in 1 case. All patients demonstrated good aesthetic and functional outcomes related to vision, speech, and oral intake at follow-up when applicable. The free ulnar forearm flap is a versatile reconstructive option that can be used to address a wide spectrum of craniofacial soft-tissue defects and offers numerous advantages over its radial counterpart.

Purpose: Free tissue transfer after lower extremity trauma is associated with notoriously high complication rates. Theoretically, the inclusion of a cutaneous paddle on muscle free flaps may improve clinical flap monitoring. The effect of skin paddle presence on muscle free flap salvage outcomes after take-back was examined., Methods: Retrospective query of our institutional free-flap registry (1979-2016) identified 362 muscle-based flaps performed for soft tissue coverage after below-knee trauma. Primary outcome measures were perioperative complications, specifically take-back indications, timing, and flap salvage rates. Univariate and multivariate regression analyses were performed where appropriate., Results: The most common flaps were latissimus dorsi (166; 45.9%), rectus abdominis (123; 34%), and gracilis (42; 11.6%) with 90 flaps (24.9%) including skin paddles. Take-backs for vascular compromise occurred in 44 flaps (12.2%), of which 39% contained a skin paddle while 61% did not. Overall salvage rate was 20.5%, with 31.8% partial failures and 47.7% total flap losses. Muscle flaps with skin paddles were more likely to return to the operating room within 48 hours postoperatively than those without (57.1% vs 18.2%, P = 0.036). After take-back, significantly more muscle flaps with skin paddles were salvaged compared with muscle flaps without paddles (35.7% vs 4.5%, P = 0.024). Similarly, more muscle-only flaps after take-back failed compared with their counterparts with skin paddles (95.5% vs 65.3%, P = 0.024)., Conclusions: Muscle flaps with a cutaneous paddle were associated with earlier return to the operating room and more successful flap salvage after take-back compared with muscle-only flaps. These findings suggest that skin paddle presence may improve clinical flap monitoring and promote recognition and treatment of microvascular compromise in lower extremity reconstruction.

Background:  Recipient vessels proximal to the zone of injury have traditionally been preferred for lower extremity reconstruction. However, more recent data have shown mixed outcomes when performing anastomoses distal to the zone of injury. We investigated the impact of recipient vessel location on free flap outcomes., Methods:  Retrospective review (1979-2016); 312 soft tissue free flaps for open tibia fractures met inclusion criteria. Flap characteristics and perioperative outcomes were examined. Systematic review identified articles evaluating anastomosis location and flap outcomes; pooled data analysis was performed., Results:  More anastomoses were performed proximal to the zone of injury (80.7%) than distal (19.3%). Distal anastomoses were not associated with increased take back rates (19.6%) compared with proximal (23.8%) anastomoses ( p  = 0.356). Regression analysis comparing proximal and distal anastomoses found no difference in partial flap failures (7.4% vs 11.9%; p  = 0.978) or total flap failures (9.3% vs 9.3%; p  = 0.815) when controlling for the presence of arterial injury, flap type, and time from injury to coverage. Systematic review yielded 11 articles with 1,245 proximal and 127 distal anastomoses for comparison. Pooled analysis ( p  = 0.58) and weighted comparative analysis ( p  = 0.39) found no difference in flap failure rates between proximal and distal groups., Conclusion:  Our results are congruent with the current lower extremity literature and demonstrate no difference in perioperative complication rates between anastomoses performed proximal or distal to the zone of injury. These findings suggest that anastomotic location choice should be based primarily on recipient vessel quality/flow and ease of access/exposure rather than orientation relative to the zone of injury., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care., Case Presentation: A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%. In August of 2015, a suitable donor was found. Complement-dependent cytotoxicity crossmatch was negative; flow cytometry crossmatch was positive to donor B cells. An induction immunosuppression strategy consisting of rabbit antithymocyte globulin, rituximab, tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone taper was designed. Total face, scalp, eyelid, ears, and skeletal subunit allotransplantation was performed without operative, immunological, or infectious complications. Maintenance immunosuppression consists of tacrolimus, MMF, and prednisone. As of posttransplant month 24, the patient has not developed acute rejection or metabolic or infectious complications., Conclusions: To our knowledge, this is the first report of targeted B cell agents used for induction immunosuppression in skin-containing vascularized composite tissue allotransplantation. A cautious approach is warranted, but early results are promising for reconstructive transplant candidates given the exceptionally high rate of acute rejection episodes, particularly in the first year, in this patient population.

Background: Considering that muscle has higher metabolic demand than fasciocutaneous tissue and can be more difficult to monitor clinically, the authors compared take-back salvage rates between fasciocutaneous and muscle free flaps for lower extremity trauma reconstruction., Methods: The authors conducted a retrospective review of 806 free flaps (1979 to 2016); 481 soft-tissue flaps performed for below-knee trauma met inclusion criteria. Primary outcome measures were perioperative complications, specifically, take-backs and flap salvage rates. Univariate and multivariate regression analysis was performed where appropriate., Results: Take-backs occurred in 71 flaps (muscle, n = 44; fasciocutaneous, n = 27) at an average of 3.7 ± 5.4 days postoperatively. Indications were venous (48 percent), arterial (31 percent), unknown (10 percent), and hematoma (10 percent). Overall outcomes were complete salvage (37 percent), partial failure (25 percent), and total failure (38 percent). Take-backs occurring within 48 hours postoperatively correlated with higher salvage rates (p = 0.022). Fasciocutaneous flaps demonstrated increased take-back rates compared with muscle flaps (p = 0.005) that more frequently occurred within 48 hours postoperatively (relative risk, 13.2; p = 0.012). Fasciocutaneous flaps were successfully salvaged more often than muscle-based flaps (p < 0.001). Multivariable regression strongly demonstrated higher risk of take-back failure for muscle flaps (relative risk, 9.42; p = 0.001), despite higher take-back rates among fasciocutaneous flaps (relative risk, 2.28; p = 0.004)., Conclusions: Compared with muscle-based flaps, fasciocutaneous flaps demonstrated earlier and more frequent take-backs for suspected vascular compromise, with higher successful take-back salvage rates. Furthermore, muscle flaps with skin paddles also demonstrated better salvage outcomes than those without. These findings may reflect a combination of lower metabolic demand and easier visual recognition of vascular compromise in fasciocutaneous tissue., Clinical Question/level of Evidence: Therapeutic, III.

Background: Left ventricular assist devices (LVADs) have become useful adjuncts in the treatment of patients with end-stage heart failure. LVAD implantation is associated with a unique set of problems; one such problem is device infection. We report our experience with flap salvage of infected and/or exposed LVAD hardware., Methods: Between 2011 and 2016, 49 patients underwent LVAD implantation at our institution. Patients were then categorized by infectious status: systemic infection not directly involving the LVAD device, hardware infection responsive to antibiotics, and exposure of LVAD hardware or device infection refractory to antibiotics requiring debridement and flap coverage., Results: Approximately 50% of device-related infections resolved with either oral or intravenous antibiotics while the other 50% necessitated debridement and coverage with healthy tissue. In total, 12 patients (24%) developed a device-related infection ranging from superficial driveline cellulitis to purulent pocket infections. Seven patients (14%) required extensive debridement and/or flap coverage., Conclusion: Early debridement and coverage of exposed hardware are crucial to successfully treating these LVAD infections., (© 2017 Wiley Periodicals, Inc.)

Objective: Driveline infection is a common complication of durable left ventricular assist device support. The majority involve the driveline exit site and can be treated with antibiotics and local wound care. Less frequently, these infections extend into deeper tissues and surgical debridement is necessary. Few studies have described the surgical strategy for treatment of deep driveline infection or have reported long-term outcomes. With a growing population of patients being implanted as destination therapy, there is an obvious need to evaluate and optimize treatment for complex driveline infections., Methods: Outcomes of patients undergoing durable left ventricular assist device implantation at a single center between 2011 and 2017 were reviewed retrospectively. Data including occurrence of driveline infection, pathogen, time to driveline infection, and treatment strategy were abstracted from the electronic medical record., Results: Driveline infection occurred in 10 (16.4%) of 61 patients at a median of 362 days (Q1 = 99, Q3 = 694) after primary left ventricular assist device implantation. Three (30.0%) of 10 driveline infections were categorized as deep and did not resolve with intravenous antibiotic therapy. In these cases, a multistage approach that included initial debridement and exteriorization of the infected driveline, followed by delayed surgical relocation of the driveline in a clean vascularized soft tissue bed, was used. Long-term device salvage was achieved in all cases., Conclusions: An aggressive surgical strategy, including debridement and formal relocation of the driveline exit site, can result in long-term device salvage after deep driveline infection. This approach is a less invasive alternative to device exchange for refractory driveline infections.

Background: Open tibia fractures are commonly stratified by the Gustilo classification, an orthopedic grading system that does not incorporate the presence of arterial injury when limb perfusion is intact. In the authors' experience, however, the presence of arterial injury appears to negatively impact microsurgical outcomes., Methods: In a retrospective review of 806 lower extremity reconstructions between 1979 and 2016, 361 soft-tissue flaps performed for Gustilo type IIIB/C coverage met inclusion criteria. Patient demographics, flap characteristics, and outcomes were analyzed., Results: Most patients suffered type IIIB [n = 332 (91.9 percent)] injuries; 29 (8.0 percent) had type IIIC injuries. Preoperative angiography [n = 243 (67.3 percent)] demonstrated arterial injury in 126 (51.8 percent); 27 arterial injuries were identified intraoperatively; and the overall incidence was 153 of 361 (42.4 percent). Complications occurred in 143 flaps (39.6 percent) and included 37 partial losses (10.2 percent) and 31 total losses (8.6 percent). Injured recipient arteries [n = 62 (17.2 percent)] had more complications (p = 0.004); specifically, increased take-backs (p = 0.009). Decreasing vessel runoff increased the risk of complications (p = 0.025), take-backs (p = 0.007), and total flap failures (p = 0.024) accordingly. Specifically, among grade IIIB injuries, controlling for age, sex, time since injury, and vein number, single-vessel runoff was associated with higher rates of complications (relative risk, 3.07; p = 0.012), take-backs (relative risk, 3.43; p = 0.013), and total flap failures (relative risk, 4.80; p = 0.010) compared with three-vessel runoff., Conclusions: Arterial injury was common among Gustilo type IIIB patients and correlated with increased reconstructive complications. Nonischemic arterial injury appears to negatively impact reconstructive outcomes and should be accounted for when considering free tissue transfer for lower extremity salvage. The authors propose a 3-2-1 modification of the Gustilo type IIIB classification to incorporate degree of arterial injury, as it appears to add prognostic value and certainly influences the reconstructive plan., Clinical Question/level of Evidence: Risk, IV.

The fabrication of large cellular tissue-engineered constructs is currently limited by an inability to manufacture internal vasculature that can be anastomosed to the host circulatory system. Creation of synthetic tissues with microvascular networks that adequately mimic the size and density of in vivo capillaries remains one of the foremost challenges within tissue engineering, as cells must reside within 200-300 μm of vasculature for long-term survival. In our previous work, we used a sacrificial microfibre technique whereby Pluronic® F127 fibres were embedded and then sacrificed within a collagen matrix, leaving behind a patent channel, which was subsequently seeded with endothelial and smooth muscle cells, forming a neointima and neomedia. We now have extended our technique and describe two approaches to synthesize a biocompatible tissue-engineered construct with macro-inlet and -outlet vessels, bridged by a dense network of cellularized microvessels, recapitulating the hierarchical organization of an arteriole, venule and capillary bed, respectively. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation., Methods: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture-seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated., Results: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture-seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel "neovessel." In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture-seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively)., Conclusion: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.

Background: Implant-based breast reconstruction is the most common reconstructive technique in the United States. Despite its popularity, saline-based tissue expansion still has its limitations, including lengthy expansion times, large uncomfortable bolus dosing, and frequent percutaneous injections/expansion visits. Ideally, a novel technology would eliminate frequent, percutaneous saline injections and allow patients to perform expansion at home, reducing the disruptive experience of current tissue expansion., Methods: Within the past 6 years, the AeroForm tissue expander system has used remotely activated carbon dioxide release as the fill medium instead of saline, eliminating many limitations of traditional tissue expanders. In this article, the authors first review the relevant literature concerning carbon dioxide-based tissue expansion in animal and human models. The authors then analyze the similarities and differences between two groundbreaking human trials (i.e., Patient Activated Controlled Expansion and AirXpanders Patient Activated Controlled Tissue Expander) with carbon dioxide-based expanders and discuss the risks and benefits associated with this new technology., Results: At their site, the authors have enrolled 34 patients using 36 experimental devices in total, and have found significantly shorter expansion and overall reconstruction times in the patient-controlled tissue expander group., Conclusions: The authors believe that carbon dioxide-based devices may play a significant role in the future of implant-based breast reconstruction, and may be widely applicable to other areas of plastic surgery that also involve tissue expansion.

Introduction: Despite a recent rise in popularity of endovascular techniques, open bypass surgery is still required for treating many lower extremity vascular lesions. Greater saphenous vein (GSV) of adequate length and caliber for successful infrainguinal lower extremity bypass is unavailable in 15% to 45% of patients. To overcome limitations imposed by absent vein due to prior use, short vessel length, or sclerotic segments, both alternate (ie, basilic and cephalic) and GSV conduits may be "spliced" together in series via venovenostomy. Although vascular surgeons typically perform a hand-sewn venovenostomy, device-based venous coupling has been performed by plastic surgeons for many years. We therefore sought to review our experience with venous coupling for segmental lower extremity bypass graft assembly., Methods: A retrospective review was performed in all patients who underwent lower extremity revascularization using autogenous vein grafts spliced together with the Synovis (Birmingham, Alabama) anastomotic coupler at a single institution over a 5-year period., Results: The anastomotic coupler device was used on 5 patients for 7 venovenostomies. The mean age of patients was 66 years, and the mean follow-up period was 751 days. Two patients were lost to follow-up, while 2 other patients died of causes unrelated to their lower extremity bypass. The average time to perform venovenostomy was 3 minutes. Three patients developed stenosis of their composite graft at a site other than the venovenostomy, who were successfully treated with either angioplasty or bypass revision. One-year primary and primary-assisted patency rates were 50% and 75%, respectively., Conclusions: Given the known benefits of the anastomotic coupling device when used for venous anastomoses in microsurgical reconstruction, transition of this device to the vascular surgery realm represents a logical progression. Although small, our series demonstrates that the anastomotic coupler can successfully be used for the formation of spliced autogenous grafts for lower extremity revascularization in the absence of adequate GSV., (© The Author(s) 2015.)

Intracranial arteriovenous malformations (AVMs) are a common cause of stroke in younger patients, and often present as intracerebral hemorrhages (ICH), associated with 10 % to 30 % mortality. Patients who present with a hemorrhage from an AVM should be initially stabilized according to acute management guidelines for ICH. The characteristics of a lesion including its size, location in eloquent tissue, and high-risk features will influence risk of rupture, prognosis, as well as help guide management decisions. Given that rupture is associated with an increased risk of 6 % re-rupture in the year following the initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured lesions only, definitive treatment is encouraged after ICH stabilization. A rest period of 2 to 6 weeks after hemorrhage is recommended before definitive treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may consist of endovascular embolization, surgical resection, radiosurgery, or a combination of these three interventions based on the lesion.

Host antibacterial responses include mechanisms that kill bacteria, but also those that protect or tolerize the host to potentially damaging antibacterial effects. We determined that Chitinase 3-like-1 (Chi3l1), a conserved prototypic chitinase-like protein, is induced by Streptococcus pneumoniae and plays central roles in promoting bacterial clearance and mediating host tolerance. S. pneumoniae-infected Chi3l1 null mice exhibit exaggerated lung injury, inflammation and hemorrhage, more frequent bacterial dissemination, decreased bacterial clearance, and enhanced mortality compared to controls. Chi3l1 augments macrophage bacterial killing by inhibiting caspase-1-dependent macrophage pyroptosis and augments host tolerance by controlling inflammasome activation, ATP accumulation, expression of ATP receptor P2X7R, and production of thymic stromal lymphopoietin and type 1, type 2, and type 17 cytokines. These data demonstrate that Chi3l1 is induced during infection, where it promotes bacterial clearance while simultaneously augmenting host tolerance, and that these roles likely contributed to the retention of Chi3l1 over species and evolutionary time., (Copyright © 2012 Elsevier Inc. All rights reserved.)

What Is Already Known About This Subject: • Angiotensin II receptor blockers improve endothelial cell-dependent vasodilation in patients with hypertension through suppression of angiotensin II type 1 receptors but may have additional and differential effects on endothelial nitric oxide synthase (eNOS) function., What This Study Adds: • The key finding from this study is that angiotensin II receptor blockers (ARBs) differentially enhanced nitric oxide (NO) release in a manner influenced by certain genetic variants of eNOS. This finding provides new insights into the effects of ARBs on endothelial cell-dependent vasodilation and eNOS function that are of high importance in vascular medicine and clinical pharmacology. AIM Angiotensin II receptor blockers (ARBs) improve endothelial cell (EC)-dependent vasodilation in patients with hypertension through suppression of angiotensin II type 1 receptors but may have additional and differential effects on endothelial nitric oxide (NO) synthase (eNOS) function. To investigate this question, we tested the effects of various ARBs on NO release in ECs from multiple donors, including those with eNOS genetic variants linked to higher cardiovascular risk., Methods: The effects of ARBs (losartan, olmesartan, telmisartan, valsartan), at 1 µm, on NO release were measured with nanosensors in human umbilical vein ECs obtained from 18 donors. NO release was stimulated with calcium ionophore (1 µm) and its maximal concentration was correlated with eNOS variants. The eNOS variants were determined by a single nucleotide polymorphism in the promoter region (T-786C) and in the exon 7 (G894T), linked to changes in NO metabolism. RESULTS All of the ARBs caused an increase in NO release as compared with untreated samples (P < 0.01, n= 4-5 in all eNOS variants). However, maximal NO production was differentially influenced by eNOS genotype. Olmesartan increased maximal NO release by 30%, which was significantly greater (P < 0.01, n= 4-5 in all eNOS variants) than increases observed with other ARBs., Conclusions: The ARBs differentially enhanced NO release in ECs in a manner influenced by eNOS single nucleotide polymorphisms. These findings provide new insights into the effects of ARBs on EC-dependent vasodilation and eNOS function., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Background: Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO(-)]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied the influence of SiNP on the platelet [NO]/[ONOO(-)] balance and platelet aggregation., Methods: Nanoparticle-platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO(-) released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy., Results: Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO(-) leading to an unfavorably low [NO]/[ONOO(-)] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size., Conclusions: The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO(-)] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets.

Background: The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells., Methods: Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO(-)) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay., Results: We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO(-). The low [NO]/[ONOO(-)] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor κB activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner., Conclusion: The [NO]/[ONOO(-)] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.

Aim: Endothelial cell (EC) dysfunction contributes to insulin resistance in diabetes and is characterized by reduced nitric oxide (NO) release, increased nitroxidative stress and enhanced inflammation. The purpose of this study was to test the effect of improved postprandial glucose control on EC function in insulin-resistant rats as compared to fasting glucose (FG) changes., Methods: Obese Zucker rats were treated with 10 mg/kg/day saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, for 4 or 8 weeks and compared to lean rats. NO and peroxynitrite (ONOO(-)) release from aortic and glomerular ECs was measured ex vivo using amperometric approaches and correlated with FG, postprandial glucose, insulin, soluble CD40 (sCD40) and L-citrulline levels., Results: Saxagliptin treatment improved NO production and reduced ONOO(-) release prior to any observed changes in FG levels. In untreated obese animals, NO release from aortic and glomerular ECs decreased by 22% and 31%, respectively, while ONOO(-) release increased by 26% and 40%. Saxagliptin increased aortic and glomerular NO release by 18% and 31%, respectively, with comparable reductions in ONOO(-) levels; the NO/ONOO(-) ratio, an indicator of NO synthase coupling, increased by >40%. Improved glycemic control was further associated with a reduction in sCD40 levels by more than ten-fold (from 300 ± 206 to 22 ± 22 pg/mL, p < 0.001)., Conclusion: These findings indicate that enhanced glycemic control with DPP4 inhibition improved NO release and reduced inflammation in a manner not predicted by FG changes alone.

Elevation of nitric oxide (NO*) can either promote or inhibit ultraviolet B light (UVB)-induced apoptosis. In this study, we determined real-time concentration of NO* and peroxynitrite (ONOO(-)) and their role in regulation of membrane integrity and apoptosis. Nanosensors (diameter 300-500 nm) were used for direct in situ simultaneous measurements of NO* and ONOO(-) generated by UVB in cultured keratinocytes and mice epidermis. An exposure of keratinocytes to UVB immediately generated ONOO(-) at maximal concentration of 190 nm followed by NO(*) release with a maximal concentration of 91 nm. The kinetics of UVB-induced NO*/ONOO(-) was in contrast to cNOS agonist stimulated NO*/ONOO(-) from keratinocytes. After stimulating cNOS by calcium ionophore (CaI), NO* release from keratinocytes was followed by ONOO(-) production. The [NO*] to [ONOO(-)] ratio generated by UVB decreased below 0.5 indicating a serious imbalance between cytoprotective NO* and cytotoxic ONOO(-)-a main component of nitroxidative stress. The NO*/ONOO(-) imbalance increased membrane damage and cell apoptosis was partially reversed in the presence of free radical scavenger. The results suggest that UVB-induced and cNOS-produced NO* is rapidly scavenged by photolytically and enzymatically generated superoxide (O(2) (-)) to produce high levels of ONOO(-), which enhances oxidative injury and apoptosis of the irradiated cells.

Background: Alterations in endothelial function may contribute to increased susceptibility of black Americans to cardiovascular disease. The ability to pharmacologically reverse endothelial dysfunction in blacks was tested with nebivolol, a beta1-selective agent with vasodilating and antioxidant properties., Methods and Results: The effects of nebivolol on endothelial nitric oxide (NO), superoxide (O2-), and peroxynitrite concentration (ONOO-) release were studied in human umbilical vein endothelial cells and iliac artery endothelial cells isolated from age-matched black and white donors. Kinetics and concentrations of NO/O2-/ONOO- were measured simultaneously with nanosensors from single cells and shown to have significant interracial differences. The rate of NO release was &5 times slower in blacks than in whites (94 versus 505 nmol . L(-1).s(-1)), whereas the rates of release were faster by &2 times for O2- and &4 times for ONOO- (22.1 versus 9.4 nmol.L(-1).s(-1) for O2- and 810 versus 209 nmol.L(-1).s(-1) for ONOO-). Pretreatment with 1.0 to 5.0 micromol/L nebivolol restored NO bioavailability in endothelial cells from black donors with concurrent reductions in O2- and ONOO- release, similar to levels in the endothelium of whites. The effects of nebivolol were dose-dependent and not observed with atenolol; similar effects were observed with apocynin, an NAD(P)H oxidase inhibitor., Conclusions: Reduced endothelial NO bioavailability in American blacks is mainly due to excessive O2- and ONOO- generation by NAD(P)H and uncoupled endothelial NO synthase. Nebivolol decreased O2- and ONOO- concentrations and restored NO bioavailability in blacks to the level recorded in cells from whites, independently of beta1-selective blockade.

The production of peroxynitrite (ONOO(-)) in the endothelium decreases NO bioavailability, decreases vasorelaxation and changes vascular tone. ONOO(-) can also influence the production of prostacyclin-another vasorelaxant. We used a nanotechnological approach (nanosensors) to elucidate the release of NO, O(2)(-), and ONOO(-) in endothelium and their effect on production of prostanoids. The basal ONOO(-) concentration near the endothelium (3-5 microm) varied from 1 to 50 nmol/L and maximal calcium ionophore stimulated ONOO(-), did not exceed 900 nmol/L. The highest ONOO(-) concentrations were produced in ischemia/reperfusion atherosclerosis, diabetes, aging and vary among different racial groups (higher in Blacks than in Whites). ONOO(-) decreased PGI(2) activity with IC(50) approximately 150 nmol/L for 8 min reaction time, but has no effect of short reaction time. Prostaglandin E(1) decreased NO, O(2)(-), and ONOO(-) by limiting Ca(2+) flux into endothelium, decreased edema and vasoconstriction during ischemia/reperfusion. In endothelium (HUVEC's) of Black's the ONOO(-) concentrations were high 750+/-50 nmol/L while the lowest concentrations of vasorelaxants were 275+/-25 nmol/L of NO, 150+/-15 pb/100 microg protein of 6-keto-PGF(1)(alpha) as compared to White's (420+/-30 and 470+/- nmol/L for ONOO(-) and NO respectively and 280+/-20 pg/100 mg protein for 6-keto-PGF(1)(alpha)).