Long-term outcomes analysis of flap-based perineal reconstruction.

BACKGROUND: High-risk patients undergoing abdominoperineal resection and pelvic exenteration may benefit from immediate flap reconstruction. However, there is currently no consensus on the ideal flap choice or patient for whom this is necessary. This study aimed to evaluate the long-term outcomes of using pedicled gracilis flaps for pelvic reconstruction and to analyze predictors of postoperative complications. METHODS: This was a retrospective review of a single reconstructive surgeon's cases between January 2012 and June 2021 identifying patients who underwent perineal reconstruction secondary to oncologic resection. Preoperative and outcome variables were collected and analyzed to determine the risk of developing minor and major wound complications. RESULTS: A total of 101 patients were included in the study with most patients (n = 88) undergoing unilateral gracilis flap reconstruction after oncologic resection. The mean follow-up period was 75 months. Of 101 patients, 8 (7.9%) developed early major complications, and an additional 13 (12.9%) developed late major complications. Minor complications developed in 33 patients (32.7%) with most cases being minor wound breakdown requiring local wound care. Most patients (n = 92, 91.1%) did not develop donor site complications. Anal cancer was significantly associated with early major complications, whereas younger age and elevated body mass index were significant predictors of developing minor wound complications. CONCLUSIONS: This study builds on our previous work that demonstrated the long-term success rate of gracilis flap reconstruction after large pelvic oncologic resections. A few patients developed donor site complications, and perineal complications were usually easily managed with local wound care, thus making the gracilis flap an attractive alternative to abdominal-based flaps.

Therapeutic Options for Migraines in the Microsurgical Patient: A Scoping Review.

BACKGROUND: There exists an increasing array of treatments proposed to prevent, alleviate, and abort symptoms of a migraine; however, for patients who undergo reconstructive microsurgery, caution must be taken to preserve vascular integrity. This study is the first-to-date scoping review of vascular and bleeding risk of current migraine therapies, with the purpose of identifying potential therapeutic agents for postoperative migraine management appropriate for microsurgical patients. METHODS: Currently available migraine therapeutics were compiled from UpToDate and the American Academy of Family Physicians. A PubMed literature review was performed for each therapeutic's effect on bleeding or vascular involvement. Data were compiled into tables of abortive, symptom-controlling and prophylactic, and non-pharmacologic treatments. Expert microsurgeons reviewed the data to provide recommendations for optimized patient care. RESULTS: Triptans and other ergot derivatives demonstrated strong evidence of vasoconstriction and were greatly advised against for immediate post-microsurgical use. Novel pharmaceutical therapies like Lasmiditan and CGRP antagonists have no literature indicating potential for vasoconstriction or hematoma and remain an investigational option for abortive medical treatment. For symptom control, acetaminophen appears the safest option, with clinical judgment and further research needed for use of NSAIDs. Alternative treatment techniques may include migraine prophylaxis with botulinum toxin injection or nutraceutical treatment via magnesium supplementation or Coenzyme Q10 administration, minimizing the need for additional medication in the postoperative setting. CONCLUSIONS: Patients undergoing reconstructive microsurgery have a unique medical profile limiting the therapeutic options available to treat migraines. This review provides preliminary evidence to be considered as a guide for prescribing therapeutics for migraine in the postoperative setting.

Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction in the Setting of Cryolipolysis.

The deep inferior epigastric artery perforator (DIEP) flap is a safe and reliable autologous breast reconstruction option for patients undergoing surgical treatment for breast cancer. Success of the procedure relies on adequate flap perfusion from perforators that travel within the subcutaneous layer of the abdominal wall. Patients who have undergone invasive abdominal wall procedures such as suction-assisted liposuction may therefore be at increased risk of postoperative complications such as flap loss and fat necrosis. In recent years, noninvasive fat-reduction techniques such as cryolipolysis have grown immensely in popularity. However, there are no data regarding outcomes for patients who have undergone DIEP flap breast reconstruction after having previously undergone abdominal cryolipolysis. The current case demonstrates that free flap breast reconstruction can be performed safely in this patient population, and that adjunct imaging modalities may improve clinical decision-making.

Locoregional Flap Closure for High-risk Multilevel Spine Surgery.

BACKGROUND: Postoperative wound complications pose a challenge to patients undergoing complex spine surgery. Long-term sequelae can be devastating including decreased quality of life, meningitis, prolonged hospital stay, and need for reoperation. Among high-risk patients, postoperative wound complications have been shown to approach 40% in the literature. The aim of this study was to identify predictive factors for postoperative complications following soft-tissue reconstruction after high-risk spine surgery with the hypothesis that it would result in significantly fewer postoperative wound complications. METHODS: A retrospective review of 67 consecutive spine operations at an academic, tertiary care center was performed, evaluating outcomes with a single plastic surgeon in conjunction with the spine surgery team. Data regarding patient demographics, perioperative risk variables, flap type, location of defect, and postoperative outcomes were obtained through retrospective chart review. Complications included soft-tissue complications and a number of reoperations. A bivariate analysis was used to identify predictors of postoperative complication. These data were compared to literature-reported averages. RESULTS: A total of 67 consecutive spinal reconstructive operations were included with a mean follow-up of 11.8 months. Thirty-seven patients (55.2%) underwent immediate reconstruction at the time of the index operation, and 30 (44.8%) underwent delayed reconstruction for secondary wound healing problems following the index operation (in which plastic surgery was not involved). The majority of both immediate (95%, n = 35) and delayed (100%, n = 30) patients was defined as high risk based on literature standards. Patients in this series demonstrated a 7.5% complication rate, compared to 18.7% complication rate in the literature. We did not find a difference between major wound complications in the immediate (8.1%) or delayed (6.7%) reconstructive setting (P > 0.99). There were no specific variables identified that predicted postoperative complications. CONCLUSION: This study illustrates a postoperative complication rate of 7.5% among patients undergoing paraspinous or locoregional muscle flap closure by plastic surgery, which is significantly lower than that reported in contemporary literature for these high-risk patients.

Neurotized Free Tissue Transfer for Foot Reconstruction: A Systematic Review.

BACKGROUND: Soft tissue reconstruction of the foot represents a complex reconstructive challenge given the unique anatomical properties of the glabrous plantar skin. For large soft tissue defects and/or complex injuries, free tissue transfer is often the optimal reconstructive modality. The decision to pursue a neurotized free flap remains controversial and an area of debate. Given the trend toward increasing use of neurotized free flaps, we performed a systematic review to determine if nerve coaptation is a beneficial adjunct to free tissue transfer. METHODS: A systematic search of the English literature using PubMed and Web of Science was performed. Studies were identified between 1985 and 2018. Manuscripts were eligible if they contained original clinical outcomes research of patients who underwent free tissue transfer to the foot or heel with neurotization. RESULTS: A total of 189 studies were identified with initial screening and 19 studies were included in our analysis. A total of 175 patients underwent free flap reconstruction to the foot; of these, 107 patients had a nerve coaptation performed. Patients who underwent neurotization had improved sensory characteristics (two-point discrimination, light touch, and pain sensation), quicker return to ambulation and activities of daily living, and decreased ulcer formation compared with those who did not. Overall complications were infrequent, with ulceration being the most common. CONCLUSION: Neurotized free flaps appear to have an overall decreased rate of ulceration, improved sensory discrimination, and quicker return to ambulation/activities of daily living in comparison to nonneurotized free flaps. However, when examining free anterolateral thigh (ALT) and free medial plantar artery (MPA) fasciocutaneous flaps, durability (i.e., frequency of ulcer formation) and functionality (ambulation and return to activities of daily living) do not appear to be significantly different between neurotized and nonneurotized flaps.

Safety Profiles of Fat Processing Techniques in Autologous Fat Transfer for Breast Reconstruction.

BACKGROUND: Autologous fat transfer is common in breast reconstruction because of its versatility for use in contour deformities. The authors examined three different fat grafting processing techniques for complications and safety profile using their institutional database. METHODS: Retrospective review was performed of patients from a single institution who had undergone autologous fat transfer following breast reconstruction from 2012 to 2016. Individuals were separated into three cohorts according to fat harvest technique: (1) centrifugation, (2) Telfa gauze, or (3) Revolve. Complications between the groups were assessed. RESULTS: A total of 267 cases of autologous fat transfer were identified (centrifugation, n = 168; Telfa, n = 44; and Revolve, n = 55). Grafting by means of centrifugation was associated with the greatest incidence of oil cysts (12.5 percent; p = 0.034), postoperative adverse events observed in the clinic (13.7 percent; p = 0.002), and total complications (25.6 percent; p = 0.001). The use of Telfa resulted in the lowest rates of oil cyst formation (0 percent; p = 0.002) and total complications (2.3 percent; p = 0.001). Grafting by means of centrifugation was also associated with the highest frequency of repeated injections among the three techniques after initial grafting (19.6 percent; p = 0.029). In contrast, Revolve demonstrated a repeated injection rate of just 5.45 percent, significantly lower when independently compared with centrifugation (p = 0.011). Multivariate analysis demonstrated that higher total graft volume (p = 0.002) and the use of centrifugation (p = 0.002) were significant risk factors for adverse events seen in the clinic postoperatively. CONCLUSIONS: Significant differences in postoperative outcomes exist between varying fat transfer techniques. Autologous fat transfer by means of centrifugation harbored the highest rates of complication, whereas Telfa and Revolve exhibited similar safety profiles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Readability, Suitability, and Complexity of Online Resources for Lower Extremity Reconstruction.

BACKGROUND: Surgical options for lower extremity reconstruction frequently include a decision between autologous free flap reconstruction and amputation. Patients rely on health education materials for information before making treatment decisions. This study evaluates the quality of online health information for lower extremity reconstruction. METHODS: We identified the top 10 Web sites for "leg amputation" and "leg free flap reconstruction." Three validated tools were used to evaluate literacy demand of materials, including (1) the Simple Measure of Gobbledygook for readability; (2) the Peter Mosenthal and Irwin Kirsch readability formula for complexity of nonprose materials such as list, graphs, charts; and (3) the Centers for Disease Control and Prevention's Clear Communication Index (Index). Differences in mean between the 2 groups were compared using Student t test. RESULTS: Average Simple Measure of Gobbledygook reading grades approximated 12th-grade level and were similar between the 2 groups. This is above the recommended level of sixth-grade health literature. Complexity scores for nonprose materials of these groups were within recommended range and corresponded to very low complexity at a fourth- to seventh-grade level. The Centers for Disease Control and Prevention index was higher for amputation literature compared with free flap reconstruction (70% vs 54%), but the difference was not statistically significant. CONCLUSIONS: Overall, online health resources for lower extremity amputation and free flap reconstruction do not meet the standard for quality and accessible health information. Free flap reconstruction resources are scarce and complex. Patients facing decisions about extremity reconstruction may not have appropriate online health resources available to them to make informed decisions.

Donor-Site Morbidity of Vascularized Bone Flaps from the Distal Femur: A Systematic Review.

BACKGROUND: Vascularized grafts from the femur, including the medial femoral condyle and medial femoral trochlea, are increasingly being used. It is critical to understand the lower extremity complications from flap harvest. METHODS: The authors searched available literature reporting on femoral flaps using PubMed, Embase, Cochrane Database, and Web of Science. After article selection, data were collected regarding demographics, procedure details, outcomes, and complications. The authors classified outcomes as good, fair, or poor based on pain, range-of-motion, sensory changes, subjective reporting, patient-reported outcomes, and other donor-site complications, including the need for additional procedures. RESULTS: Two hundred twenty articles were identified. Forty-five met criteria for review, with data available for 283 patients. No patients had range-of-motion deficits beyond 1 year. Two percent of patients (six of 283) required additional donor-site procedures, with one report of a femur fracture after medial femoral condyle harvest. Only one study on 45 medial femoral trochlea patients presented patient-reported outcomes regarding the knee. Few objective data were presented. Twenty-eight articles presented adequate complication data for 252 patients to be rated as good, fair, or poor. Overall, 89 percent had good outcomes without donor-site complications. Of the 176 medial femoral condyle patients with outcomes reported, 92 percent had good outcomes; and 71 percent of the 48 medial femoral trochlea patients had good outcomes reported. CONCLUSIONS: Overall, the reported donor-site morbidity from medial femoral condyle and medial femoral trochlea harvest is low. Chronic knee pain and sensory changes are most frequently reported, especially in medial femoral trochlea patients.

Avascular necrosis of the humeral head following bilateral upper extremity vascular composite allotransplantation: a case report.

Vascularised composite allotransplantation (VCA) represents an exciting and emerging field in plastic and reconstructive surgery. Despite the generally good functional and psychosocial outcomes, multiple complications can be associated with the procedure. The authors describe a case of avascular necrosis of the humeral head following successful upper extremity VCA.

Topical Vasodilators in Microsurgery: What Is the Evidence?

Background Topical vasodilators are frequently used during free tissue transfer to prevent and treat vasospasm and microvascular thrombosis. A variety of agents have been studied and are available, yet most microsurgeons select an agent based on anecdotal evidence or personal training. Our aim was to review the literature on topical vasodilators so microsurgeons can make more informed decisions about which agent to use. Methods A systemic review of the literature was performed on PubMed, EMBASE, and Google Scholar using keywords "topical vasodilator," "antispasmodic," "vasospasm," "free flaps," and "microsurgery." Studies were included if they provided a comparative quantitative assessment of topical vasodilators and were written in English. In vitro, in vivo, and clinical studies were included. Results A total of 15 studies were identified and included in our analysis. The three most common classes of topical vasodilator include local anesthetics, phosphodiesterase inhibitors, and calcium channel blockers (CCBs). Of the most commonly used topical vasodilators, CCBs (nifedipine and verapamil) were most effective followed by papaverine and lidocaine. Conclusion The most effective topical vasodilators appear to be CCBs including nifedipine, nicardipine, and verapamil. Evidence suggests that these agents are more effective than papaverine and lidocaine solutions that are commonly used. Future research should directly compare individual CCBs to assess the most effective agent. Studies to date have focused on vessels other than those used by microsurgeons, and therefore further studies specific to these vessels are warranted.

Proximal Interphalangeal Joint Fibromatosis After Pyrocarbon Implant Insertion: A Case Report.

Background: Pyrocarbon implants represent an increasingly popular method to treat proximal interphalangeal joint dysfunction. To this point, no association has been shown between pyrocarbon biomaterials and fibromatosis. We present a potentially serious and destructive complication associated with pyrocarbon arthroplasty. Methods: We demonstrate a clinical case involving pyrocarbon arthroplasty and subsequent fibromatosis development in an otherwise healthy 23-year-old female. To present this association, we illustrate the diagnostic workup involved in a rapidly expanding soft tissue mass of the hand and explain the appropriate treatment. Results: Pyrocarbon arthroplasty was associated with development of locally destructive fibromatosis confirmed by histopathological examination. Treatment involved wide resection with preservation of local structures. Conclusion: We describe the first association between fibromatosis and pyrocarbon biomaterial. Due to fibromatosis destructive effects, clinicians should be aware of potential complications associated with these materials and know how to accurately diagnose and treat these lesions.

Early Development of the Mouse Morphome.

INTRODUCTION: Analytical morphomics focuses on extracting objective and quantifiable data from clinical computed tomography (CT) scans to measure patients' frailty. Studies are currently retrospective in nature; therefore, it would be beneficial to develop animal models for well-controlled, prospective studies. The aim of this study is to develop an in vivo microCT protocol for the longitudinal acquisition of whole-body images suitable for morphomic analyses of bone. METHODS: The authors performed phantom studies on 2 microCT systems (Inveon and CT120) to study tissue radiodensity and further characterize system performance for collecting animal data. The authors also describe their design of a phantom-immobilization device using phantoms and an ovariectomized (OVX) mouse. RESULTS: The authors discovered increased consistency along the z-axis for scans acquired on the Inveon compared with CT120, and calibration by individual slice reduces variability. Objects in the field of view had more impact on measurement acquired using the CT120 compared with the Inveon. The authors also found that using the middle 80% of slices for data analysis further decreased variability, on both systems. Moreover, bone-mineral-density calibration using the QCT Pro Mini phantom improved bone-mineral-density estimates across energy spectra, which helped confirm our technique. Comparison of weekly body weights and terminal uterine mass between sham and OVX groups validated our model. DISCUSSION: The authors present a refined microCT protocol to collect reliable and objective data. This data will be used to establish a platform for research animal morphomics that can be used to test hypotheses developed from clinical human morphomics.

The Systemic Effect of Burn Injury and Trauma on Muscle and Bone Mass and Composition.

BACKGROUND: By understanding the global inflammatory effects on distant myopathies, surgeons can better guide the rehabilitative process for burn patients. The authors tested the systemic effect of burn injury on distant injured muscle and native bone using immunohistochemistry and validated a new morphometric analytic modality to reproducibly quantify muscle atrophy using computed tomographic imaging. METHODS: In vivo studies were performed on C57/BL6 mice using an Achilles tenotomy with concurrent burn injury model. Total muscle and bone (tibia and fibula) volume/density were quantified near the site of Achilles tenotomy using micro-computed tomography at 5, 7, and 9 to 12 weeks after surgery. The impact of burn injury on the inflammatory cascade [nuclear factor (NF)-κB, p-NF-κB] and the interconnected protein catabolism signaling pathway (Atrogin-1) was assessed by immunohistochemistry. RESULTS: Muscle volume and density at the site of Achilles tenotomy in burned mice were significantly diminished compared with nonburned mice at 5 weeks and 9 to 12 weeks. Similar decreases in muscle volume and density were observed when comparing tenotomy to no tenotomy. Cortical bone health remained stable in burn/tenotomy mice compared with tenotomy. Muscle atrophy was associated with up-regulation of p-NF-κB, NF-κB, and Atrogin-1 assessed by immunohistochemistry. CONCLUSIONS: Burn injury significantly decreases muscle volume and density. Increased muscle atrophy using our computed tomographic morphometric analysis correlated with a significant increase in intramuscular inflammatory markers and proteolysis enzymes. This study demonstrates a unique characterization of how burn injuries may worsen local myopathy. Moreover, it provides a novel approach for quantifying muscle atrophy over an expanded period.

Abdominal wall dynamics after component separation hernia repair.

BACKGROUND: The component separation technique (CST) is an important technique now used frequently in complex ventral hernia repair (VHR). Although this technique has demonstrated superior success rates, there is a paucity of research describing how release of the external obliques coupled with rectus myofascial advancement alters the morphology of the abdominal architecture. In this study, we apply the new concept of analytic morphomics to describe the immediate changes in morphology of the abdomen that take place after VHR by CST. METHODS: We identified 21 patients who underwent VHR by CST and received both preoperative and postoperative computed tomography scans between 2004 and 2009 in our clinical database. The surgical technique involved incisional release of the external oblique muscle lateral to the linea semilunaris with rectus abdominis myofascial advancement in all patients. Using semiautomated morphomic analysis, we measured the pre- and post-operative dimensions of the abdominal wall including the anterior-posterior distance from the anterior vertebra-to-skin and fascia along with the circumferential area of the skin and fascial compartments. Paired Student t-tests were used to compare pre- and post-operative values. RESULTS: After hernia repair, there was a decrease in the anterior vertebra-to-skin distance (16.6 cm-15.8 cm, P = 0.007). There were also decreases in total body area (968.0 cm(2)-928.6 cm(2), P = 0.017) and total body circumference (113.6 cm-111.4 cm, P = 0.016). The distance from fascia to skin decreased as well, almost to the point of statistical significance (3.3 cm-2.9 cm, P = 0.0505). Interestingly, fascia area and circumference did not decrease significantly after the operation (578.2 cm(2)-572.5 cm(2), P = 0.519, and 89.1 cm-88.6 cm, P = 0.394, respectively). CONCLUSIONS: Morphomic analysis can be used to compare and pre- and post-operative changes in patients undergoing abdominal surgery. Our study demonstrates that component separation affects the dimensions of the entire abdomen, but leaves the fascia area and circumference relatively unchanged. These changes in the abdominal wall may help explain the muscular changes observed as a result of this operation and demonstrate that this is a functional operation that restores fascial area. By better defining the effects of this procedure, we can better understand the reason for its clinical success.

Morphomic analysis as an aid for preoperative risk stratification in patients undergoing major head and neck cancer surgery.

BACKGROUND: Patients undergoing major head and neck cancer surgery (MHNCS) may develop significant postoperative complications. To minimize the risk of complications, clinicians often assess multiple measures of preoperative health in terms of medical comorbidities. One emerging method to decrease surgical complications is preoperative assessment of patient frailty measured by specific tissue characteristics. We hypothesize that morphomic characteristics of the temporalis region serve as predictive markers for the development of complications after MHNCS. METHODS: We performed a retrospective review of 69 patients with available computed tomography (CT) imaging who underwent MHNCS from 2006-2012. To measure temporalis region characteristics, we used morphomic analysis of available preoperative CT scans to map out the region. All available CT scans had been performed as part of the patient's routine work-up and were not ordered for morphomic analysis. We describe the correlation among temporalis fat pad volume (TFPV), mean zygomatic arch thickness, and incidence of postoperative complications. RESULTS: We noted significant difference in the zygomatic bone thickness and TFPV between patients who had medical complications, surgical complications, or total major complications and those who did not. Furthermore, by use of binary logistic regression, our data suggest decreased TFPV and zygomatic arch thickness are stronger predictors of developing postoperative complications than previously studies preoperative characteristics. CONCLUSIONS: We describe morphomic analysis of the temporalis region in patients undergoing MHNCS to identify patients at risk for complications. Regional anatomic morphology may serve as a marker to objectively determine a patient's overall health. Use of the temporalis region is appropriate in patients undergoing MHNCS because of the availability of preoperative scans as part of routine work up for head and/or neck cancer.

Role of anatomical region and hypoxia on angiogenic markers in adipose-derived stromal cells.

BACKGROUND: Recent research into adipose-derived stem cells (ASCs) suggests that anatomical location has a major impact on the metabolic profile and differentiation capacity of ASCs. By having a better understanding of how various ASCs respond to cellular stressors such as hypoxia, which are induced during routine surgical procedures, we can facilitate future development of cell-based therapies to improve wound healing. PATIENTS AND METHODS: Human ASCs were isolated from the superficial and deep adipose layers of four patients undergoing elective abdominoplasty. ASCs were cultured in hypoxic (1% O2, 5% CO2, and 94% N2) conditions. After 12 and 48 hours, ASCs were assessed for markers of angiogenesis by mRNA levels of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B), and hypoxia inducible factor 1 α (HIF-1α). Western blot analysis was performed to assess levels of VEGF-A, p-NF-κB, and NF-κB. In addition, in vitro analysis of angiogenesis was performed using Matrigel assay (BD Biosciences, Franklin Lakes, NJ). RESULTS: We observed significant increases in deep ASC's VEGF-A, VEGF-B, and HIF-1α mRNA expression compared with the superficial layer after 24-hour hypoxia (p < 0.05). Similar results were found when examining protein expression levels, with the deep ASCs expressing significantly larger amounts of VEGF-A and p-NF-κB (p < 0.05) compared with the superficial layer. CONCLUSION: Our results suggest that significant variations exist in the angiogenic profile of superficial and deep ASCs. We demonstrate that superficial ASCs are less prone to transcribe potent chemokines for angiogenesis, such as VEGF-A, VEGF-B, and HIF-1α and are less likely to translate VEGF-A and NF-κB. This may help with the selection of specific stem cell donor sites in future models for stem cell therapy.

Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer.

Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.

Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research.