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Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that affects 63 in every 100,000 Americans. Its etiology remains unknown, although inflammatory pathways appear...

Objective: After injury, humans and other mammals heal by forming fibrotic scar tissue with diminished function, and this healing process involves the dynamic interplay between resident cells withi...

Arteriovenous (AV) fistulas for hemodialysis can lead to cardiac volume loading and increased serum brain natriuretic peptide (BNP) levels. Whether short-term AV loop placement in patients undergoing microsurgery has an impact on cardiac biomarkers and circulating microRNAs (miRNAs), potentially indicating an increased hemodynamic risk, remains elusive. Fifteen patients underwent AV loop placement with delayed free flap anastomosis for microsurgical reconstructions of lower extremity soft-tissue defects. N-terminal pro-BNP (NT-proBNP), copeptin (CT-proAVP), and miRNA expression profiles were determined in the peripheral blood before and after AV loop placement. MiRNA expression in the blood was correlated with miRNA expression from AV loop vascular tissue. Serum NT-proBNP and copeptin levels exceeded the upper reference limit after AV loop placement, with an especially strong NT-proBNP increase in patients with preexistent cardiac diseases. A miRNA signature of 4 up-regulated (miR-3198, miR-3127-5p, miR-1305, miR-1288-3p) and 2 down-regulated miRNAs (miR30a-5p, miR-145-5p) which are related to cardiovascular physiology, showed a significant systemic deregulation in blood and venous tissue after AV loop placement. AV loop placement causes serum elevations of NT-proBNP, copeptin as well as specific circulating miRNAs, indicating a potentially increased hemodynamic risk for patients with cardiovascular comorbidities, if free flap anastomosis is delayed.

Breast cancer resulting from a genetic mutations, such as BRCA1 or BRCA2, is seen in 5 to 10 percent of patients. More widespread genetic testing has increased the number of affected women undergoing prophylactic mastectomy and oophorectomy. Recent studies have yielded mixed results regarding complication rates after combined breast and ovarian operations. The authors compared surgical outcomes of breast operations performed in combination with salpingo-oophorectomies or as separate procedures.The authors retrospectively analyzed surgical complications and length of hospital stay in 145 female patients, from which 87 had undergone combined breast surgery and salpingo-oophorectomy, and 58 had undergone these procedures separately. Multivariate logistic regression models were used to calculate odds ratios and 95 percent confidence intervals.Patients undergoing combined breast and ovarian operations experienced higher rates of overall complications (46.5 percent versus 19 percent; p0.001), infections (22.2 percent versus 8.6 percent; p0.05), and delayed wound healing (13.2 percent versus 0 percent; p0.05) related to the breast surgery, when compared with patients undergoing separate procedures. Multivariate logistic regression analysis confirmed a significant association between combined surgery and overall postoperative complications (OR, 5.87; 95 percent CI, 2.03 to 16.91; p = 0.02). Patients undergoing tissue expander-based breast reconstruction combined with ovarian surgery had significantly longer hospital stays compared to patients undergoing separate procedures (3.5 days versus 1.8 days; p0.001).The authors' data indicate that combining breast and ovarian operations is associated with a higher risk of postoperative complications related to the breast procedure and increases the duration of hospital stay in patients with tissue expander-based reconstructions. The authors' study provides valuable information for preoperative counseling of patients considering both breast and ovarian surgery.Therapeutic, III.

Background MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. While acquired changes of miRNA and mRNA profiles in cancer have been extensively studied, little is known about expression changes of circulating miRNAs and messenger RNAs (mRNA) in monogenic constitutional anomalies affecting several organ systems, like Marfan syndrome (MFS). We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy. Methods MiRNA and mRNA expression profiles were determined in blood samples from MFS patients (n = 7) and from healthy volunteer controls (n = 7) by microarray analysis. Enrichment analyses of altered mRNA expression were identified using bioinformatic tools. Results A total of 28 miRNAs and 32 mRNAs were found to be significantly altered in MFS patients compared to controls (> 2.0-fold change, adjusted P

Objective: To develop a novel approach for tissue engineering of soft-tissue flaps suitable for free microsurgical transfer, using an injectable nanofiber hydrogel composite (NHC) vascularized by an arteriovenous (AV) loop. Approach: A rat AV loop model was used for tissue engineering of vascularized soft-tissue flaps. NHC or collagen-elastin (CE) scaffolds were implanted into isolation chambers together with an AV loop and explanted after 15 days. Saphenous veins were implanted into the scaffolds as controls. Neoangiogenesis, ultrastructure, and protein expression of SYNJ2BP, EPHA2, and FOXC1 were analyzed by immunohistochemistry and compared between the groups. Rheological properties were compared between the two scaffolds and native human adipose tissue. Results: A functional neovascularization was evident in NHC flaps with its amount being comparable with CE flaps. Scanning electron microscopy revealed a strong mononuclear cell infiltration along the nanofibers in NHC flaps and a trend toward higher fiber alignment compared with CE flaps. SYNJ2BP and EPHA2 expression in endothelial cells (ECs) was lower in NHC flaps compared with CE flaps, whereas FOXC1 expression was increased in NHC flaps. Compared with the stiffer CE flaps, the NHC flaps showed similar rheological properties to native human adipose tissue. Innovation: This is the first study to demonstrate the feasibility of tissue engineering of soft-tissue flaps with similar rheological properties as human fat, suitable for microsurgical transfer using an injectable nanofiber hydrogel composite. Conclusions: The injectable NHC scaffold is suitable for tissue engineering of axially vascularized soft-tissue flaps with a solid neovascularization, strong cellular infiltration, and biomechanical properties similar to human fat. Our data indicate that SYNJ2BP, EPHA2, and FOXC1 are involved in AV loop-associated angiogenesis and that the scaffold material has an impact on protein expression in ECs.

BACKGROUND Reinforcement of the abdominal wall with synthetic mesh in autologous breast reconstruction using abdominal free tissue transfer decreases the risk of bulging and herniation. However, the impact of the plane of mesh placement on donor site complications has not yet been investigated. METHODS We performed a retrospective analysis of 312 patients who had undergone autologous breast reconstruction with muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps or deep inferior epigastric perforator (DIEP) flaps as well as polypropylene mesh implantation at the donor site. Donor site complications were compared among patients with different flap types and different mesh positions including overlay (n = 90), inlay and overlay (I-O; n = 134), and sublay (n = 88). RESULTS Abdominal hernias occurred in 2.86% of patients who had undergone MS-TRAM reconstructions and in 2.63% of patients who had undergone DIEP reconstructions. When comparing patients with different mesh positions, donor site complications occurred in 14.4% of patients with overlay mesh, 13.4% of patients with I-O mesh, and 10.2% of patients with sublay mesh (P = 0.68). Abdominal hernias occurred in 4.44% of patients with overlay mesh, 2.24% of patients with I-O mesh, and 2.27% of patients with sublay mesh (P = 0.69). Multivariable logistic regression analysis did not identify a significant association between mesh position and hernia rates as well as wound complications. CONCLUSIONS Our data indicate that the plane of synthetic mesh placement in relation to the rectus abdominis muscle does not impact the rate of postoperative donor site complications in patients undergoing breast reconstruction with MS-TRAM or DIEP flaps.

Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1., Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.

Cells and tissue within injured organs undergo a complicated healing process that still remains poorly understood. Interestingly, smaller organisms respond to injury with tissue regeneration and restoration of function, while humans and other large organisms respond to injury by forming dysfunctional, fibrotic scar tissue. Over the past few decades, allometric scaling principles have been well established to show that larger organisms experience exponentially higher tissue forces during movement and locomotion and throughout the organism's lifespan. How these evolutionary adaptations may affect tissue injury has not been thoroughly investigated in humans. We discuss how these adapations may affect healing and demonstrate that blocking the most evolutionary conserved biologic force sensor enables large organisms to heal after injury with true tissue regeneration. Future strategies to disrupt tissue force sensors may unlock the key to regenerating after injury in a wide range of organ systems.

Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known proangiogenic and immunomodulatory paracrine effects. Our laboratory has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their proangiogenic capacity

Background In elderly patients, complex soft tissue defects are increasingly observed due to the prolonged life expectancy and accompanying comorbidities. The aim of this study is to evaluate whether free tissue transfer is safe in very old patients without additional risk and complications. Methods All patients older than 65 years undergoing free tissue transfer between November 2007 and September 2016 were reviewed in a retrospective study. Two cohorts were compared regarding perioperative morbidity and postoperative outcome (cohort 1 [old patients, ages 65–79]; cohort 2 [very old patients, ages ≥ 80]). Results In total, 256 patients were included in the study (cohort 1 [n = 217]; cohort 2 [n = 39]). Overall, 262 free flaps were performed due to a second microsurgical reconstruction in six cases. No statistically significant differences between cohorts were observed regarding surgical complications, total flap losses, and mortality. Detailed evaluation of cohort 2 revealed a significant learning curve during the observation period regarding the perioperative management and procedure of soft tissue reconstruction: operation length as well as postoperative intensive care unit stay decreased significantly over time (p Conclusion Our study showed that age is not associated with an increased risk of postoperative complications. Reliable muscle free flaps, two-stage procedures, and safe vascular supply are important strategic aspects to achieve microvascular tissue transfer with high success rates in geriatric patients.

Quality of life (QOL) is an important outcome measure after ventral hernia repair (VHR). The Hernia-Related QOL Survey (HerQLes) is a specific survey tool for QOL after VHR. Studies comparing QOL in patients with biologic mesh repairs (BMRs) and synthetic mesh repairs (SMRs) are lacking.A survey based on the HerQLes was administered via e-mail to 974 patients who had undergone VHR at Stanford Medical Center. From 175 patients who were included in the study, the mean HerQLes scores and postoperative complications were compared between patients with suture repairs (SR), BMR, SMR, with and without component separation, and different types of SMR.Quality of life was lower in patients with hernias of 50 cm or greater, obesity, history of tobacco use, previous abdominal surgeries, hernia recurrences, and postoperative complications (P0.05). Patients with SR and SMR had a comparable QOL (71.58 vs 70.12, P = 0.75). In patients with Modified Ventral Hernia Working Group grade 2 hernias, a significantly lower QOL was found after BMR compared with SMR. Postoperative complications did not significantly differ between the groups. Recurrence rates were comparable between MR (10.4%) and SR (8.3%, P = 0.79), but higher in BMR (21.7%) compared with SMR (6.6%, P0.05).Previous abdominal surgeries, previous hernia repairs, tobacco use, and hernia sizes of 50 cm or greater negatively affect QOL after VHR. Our data indicate that QOL is comparable between patients with SMR and SR, however, is lower in patients with Modified Ventral Hernia Working Group grade 2 and BMR compared with SMR, raising the benefit of BMR in light of its higher cost into question.

BACKGROUND:MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD. METHODS:miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools. RESULTS:Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p

Cryopreserved human skin allografts (CHSAs) are used for the coverage of major burns when donor sites for autografts are insufficiently available and have clinically shown beneficial effects on chronic non-healing wounds. However, the biologic mechanisms behind the regenerative properties of CHSA remain elusive. Furthermore, the impact of cryopreservation on the immunogenicity of CHSA has not been thoroughly investigated and raised concerns with regard to their clinical application. To investigate the importance and fate of living cells, we compared cryopreserved CHSA with human acellular dermal matrix (ADM) grafts in which living cells had been removed by chemical processing. Both grafts were subcutaneously implanted into C57BL/6 mice and explanted after 1, 3, 7, and 28 days (n = 5 per group). A sham surgery where no graft was implanted served as a control. Transmission electron microscopy (TEM) and flow cytometry were used to characterise the ultrastructure and cells within CHSA before implantation. Immunofluorescent staining of tissue sections was used to determine the immune reaction against the implanted grafts, the rate of apoptotic cells, and vascularisation as well as collagen content of the overlaying murine dermis. Digital quantification of collagen fibre alignment on tissue sections was used to quantify the degree of fibrosis within the murine dermis. A substantial population of live human cells with intact organelles was identified in CHSA prior to implantation. Subcutaneous pockets with implanted xenografts or ADMs healed without clinically apparent rejection and with a similar cellular immune response. CHSA implantation largely preserved the cellularity of the overlying murine dermis, whereas ADM was associated with a significantly higher rate of cellular apoptosis, identified by cleaved caspase-3 staining, and a stronger dendritic cell infiltration of the murine dermis. CHSA was found to induce a local angiogenic response, leading to significantly more vascularisation of the murine dermis compared with ADM and sham surgery on day 7. By day 28, aggregate collagen-1 content within the murine dermis was greater following CHSA implantation compared with ADM. Collagen fibre alignment of the murine dermis, correlating with the degree of fibrosis, was significantly greater in the ADM group, whereas CHSA maintained the characteristic basket weave pattern of the native murine dermis. Our data indicate that CHSAs promote angiogenesis and collagen-1 production without eliciting a significant fibrotic response in a xenograft model. These findings may provide insight into the beneficial effects clinically observed after treatment of chronic wounds and burns with CHSA.

Shared decision-making is a key component of patient-centered care and has been shown to improve patient satisfaction and quality of life. Herein, we study the impact of a standardized patient education class for prospective breast reconstruction patients on clinic efficiency, access to care, and perception on shared decision-making.The number of new patient consultations per clinic, as well as average duration of the first individual clinic encounter, was compared before and after the introduction of a standardized education class given by the senior author to all new breast reconstruction patients. To evaluate patients' perception of shared decision-making, the 9-item Shared Decision-Making Questionnaire (SDM-Q9) and the Satisfaction with Information scale of the BREAST-Q Reconstruction Module were electronically distributed among the patients and compared between the two groups.Introduction of the patient education class was associated with a significant reduction in the duration of new patient encounters compared to historic controls (31.8 min vs. 53.5 min, p 0.01) along with permitting a 43% increase in new patient visits. No differences in self-perceived patient education and autonomy were seen between class participants and historic controls in the SDM-Q9 scores (p = 0.58) and BREAST-Q scores (p = 0.14).The introducing a standardized patient education class translated into a significant reduction in the duration of individual new patient encounters, thereby increasing patient access to care, while maintaining high-quality standards of self-perceived patient education and shared decision-making.

Background Success of free tissue transfer depends on standardized intraoperative flap design, microsurgical technique, and postoperative monitoring. We sought to investigate whether laser speckle imaging (LSI) is suitable for optimization of intraoperative flap design and postoperative monitoring of free flaps with skin paddles. Methods Skin perfusion was assessed with LSI in 27 free flaps after dissection at the donor site, after anastomosis at the recipient site, after inset and on postoperative days (POD) 1, 5, and 10. Skin perfusion of the whole flap (ROI [region of interest]-1) and the area over the pedicle (ROI-2) were compared between patients with and without postoperative complications (POC+ and POC − , respectively). A receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff for perfusion during LSI-guided microsurgery. Results In flaps without or only minor POC, intraoperatively measured perfusion over ROI-2 was significantly higher compared with ROI-1, whereas no significant differences were found for flaps with major POC. Perfusion of ROI-1 and 2 intraoperatively and on POD 1 was significantly lower in the POC+ compared with the POC− group (p 0.8 for identification of flaps with major POC. Conclusion LSI is an easy to use, noninvasive technique for identification of malperfused areas in free flaps, thus allowing for intraoperative decision-making on flap dimensions and postoperative monitoring. LSI therefore is a valuable tool for perfusion assessment with a high potential to become an established part of microsurgical practice.

BACKGROUND The optimal time for flap anastomosis to an arteriovenous loop remains controversial. Whether perforator flaps and axially vascularized muscle or fasciocutaneous flaps lead to comparable outcomes in conjunction with arteriovenous loops has not been investigated. METHODS Medical records from 103 patients undergoing arteriovenous loop reconstruction (76 one-stage and 27 two-stage) between 2007 and 2017 were reviewed. Postoperative outcomes were compared between one- and two-stage arteriovenous loop reconstructions and different types of free flaps. RESULTS Rates of flap thrombosis, major wound complications, and flap failure did not differ significantly between one- and two-stage arteriovenous loop reconstructions (14.47 percent versus 11.11 percent, p = 1.00; 30.26 percent versus 25.93 percent, p = 0.67; and 10.53 percent versus 7.41 percent, p = 1.00). For two-stage arteriovenous loop reconstructions, the time interval between arteriovenous loop placement and flap anastomosis was a predictor for thrombotic events (OR, 1.31; p < 0.05). Anterolateral thigh flaps in conjunction with arteriovenous loops showed higher failure rates (33.33 percent) compared with all other flaps (6.59 percent) (p < 0.05) and combined latissimus dorsi and parascapular flaps (0 percent) (p < 0.05). Thrombosis rates were higher in anterolateral thigh flaps (33.33 percent) compared with all other flaps (10.99 percent; p = 0.056), and combined latissimus dorsi and parascapular flaps (0 percent; p < 0.05). CONCLUSIONS Two-stage arteriovenous loop reconstructions do not lead to increased postoperative complications compared to one-stage arteriovenous loop reconstructions and may be favorable in complicated cases because of shorter operative times. To avoid an increased thrombosis risk, flap anastomosis should not be delayed beyond 10 days in two-stage arteriovenous loop reconstructions. Anterolateral thigh flaps are less suitable for arteriovenous loop reconstructions because of higher complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

BACKGROUND Botulinum toxin treatment for forehead wrinkles has been extensively studied and found to be a safe and reproducible procedure. However, the effect on the position of the eyebrows, which relies on the dynamic positioning of the treated muscles, has received less attention and has not been studied with 3-dimensional (3D) technology. OBJECTIVES The authors sought to evaluate the changes of eyebrow position after standardized botulinum toxin treatment of glabella or glabella and frontalis muscles with 3D imaging. METHODS In a prospective study, 2 groups of adult females were treated with botulinum toxin A at the glabella only (G) or at the glabella and the frontalis muscle (F/G). The brow position was measured at 5 positions with 3D photography before injection and 2 weeks, 3 months, and 6 months after injection. Results were statistically analyzed and related to patient age. RESULTS In the F/G group, the brow descended significantly almost across the whole brow length after 2 weeks. The descent lessened after 3 months and moved medially. No clear trend was evident in the G group. There was no significant change attributed to patient age in both groups. CONCLUSIONS Botulinum toxin treatment of the glabella and frontalis muscle impacts the position and configuration of the eyebrow. The degree of change is affected by the amount of frontalis weakening rather than by treatment of the glabella. While age in general is not a reliable predictor, individual factors play the major role in how pronounced a change of the brow can be expected. LEVEL OF EVIDENCE: 2

Background Limb salvage in patients with peripheral vascular disease (PVD) and soft tissue defects often requires both a restoration of blood flow to the lower extremity and soft tissue coverage. Outcomes of free tissue transfer may be affected by vein grafts, which can be used for the placement of an autologous venous bypass or an arteriovenous (AV) loop leading to different hemodynamic situations. The purpose of this study was to investigate whether free flap anastomosis to a bypass or an AV loop can be performed with comparable results. Methods We performed a matched-pair analysis of 22 patients with PVD undergoing free flap reconstructions of the lower extremity with end-to-side anastomosis to an autologous venous bypass (n = 11, 1 female and 10 male patients) or an AV loop (n = 11, 2 female and 9 male patients). Defects caused by trauma, infection, ulcer, or fasciotomy were reconstructed in each group with 5 muscle-based flaps, 3 parascapular flaps, 2 anterolateral thigh (ALT) flaps, and 1 conjoined latissimus dorsi and parascapular flap. Postoperative complications including thromboses, flap failures, wound complications, and hematomas were compared. Results Postoperative complication rates including 1 venous pedicle thrombosis (9%vs. 0%, P = 1.0), minor (18% vs. 9%, P = 1.0) and major wound complications (45% vs. 27%, P = .69) as well as hematomas (27% vs. 36%, P = 1.0) did not show relevant differences between the groups. Flap failures were absent in both groups. Conclusion In patients with PVD, autologous venous bypass grafts may be used for end-to-side anastomoses of free flaps, with postoperative outcomes being comparable to AV loop reconstructions.

Background The placement of arteriovenous loops can enable microvascular anastomoses of free flaps when recipient vessels are scarce. In animal models, elevated fluid shear stress in arteriovenous loops promotes neoangiogenesis. Anecdotal reports in patients indicate that vein grafts used in free flap reconstructions of ischemic lower extremities are able to induce capillary formation. However, flow-stimulated angiogenesis has never been systematically investigated in humans, and it is unclear whether shear stress alters proangiogenic signaling pathways within the vascular wall of human arteriovenous loops. Methods Eight patients with lower extremity soft-tissue defects underwent two-stage reconstruction with arteriovenous loop placement, and free flap anastomoses to the loops 10 to 14 days later. Micro-RNA (miRNA) and gene expression profiles were determined in tissue samples harvested from vein grafts of arteriovenous loops by microarray analysis and quantitative real-time polymerase chain reaction. Samples from untreated veins served as controls. Results A strong deregulation of miRNA and gene expression was detected in arteriovenous loops, showing an overexpression of angiopoietic cytokines, oxygenation-associated genes, vascular growth factors, and connexin-43. The authors discovered inverse correlations along with validated and bioinformatically predicted interactions between angiogenesis-regulating genes and miRNAs in arteriovenous loops. Conclusions The authors' findings demonstrate that elevated shear stress triggers proangiogenic signaling pathways in human venous tissue, indicating that arteriovenous loops may have the ability to induce neoangiogenesis in humans. The authors' data corroborate the nutrient flap hypothesis and provide a molecular background for arteriovenous loop-based tissue engineering with potential clinical applications for soft-tissue defect reconstruction.

Soft tissue sarcomas occur most commonly in the lower and upper extremities. The standard treatment is limb salvage surgery combined with radiotherapy. Postoperative radiotherapy is associated with wound complications. This systematic review aims to summarise the available evidence and review the literature of the last 10 years regarding postoperative wound complications in patients who had limb salvage surgical excision followed by direct closure vs flap coverage together with postoperative radiotherapy and to define the optimal timeframe for adjuvant radiotherapy after soft tissue sarcomas resection and flap reconstruction. A literature search was performed using PubMed. The following keywords were searched: limb salvage, limb-sparing, flaps, radiation therapy, radiation, irradiation, adjuvant radiotherapy, postoperative radiotherapy, radiation effects, wound healing, surgical wound infection, surgical wound dehiscence, wound healing, soft tissue sarcoma and neoplasms. In total, 1045 papers were retrieved. Thirty-seven articles were finally selected after screening of abstracts and applying dates and language filters and inclusion and exclusion criteria. Plastic surgery provides a vast number of reconstructive flap procedures that are directly linked to decreasing wound complications, especially with the expectant postoperative radiotherapy. This adjuvant radiotherapy is better administered in the first 3-6 weeks after reconstruction to allow timely wound healing and avoid local recurrence.

The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.Samples from 84 patients (33 tricuspid, 32 bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.Our data suggest that GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different.

Journal Article; Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue. Yes