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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (O2˙−) to produce high levels of ONOO−, which enhances oxidative injury and apoptosis of the irradiated cells. [ABSTRACT FROM AUTHOR]

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. 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). 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%). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 µ m, on NO release were measured with nanosensors in human umbilical vein ECs obtained from 18 donors. NO release was stimulated with calcium ionophore (1 µ m) 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. [ABSTRACT FROM AUTHOR]