Search

An excess of osteoclastogenesis significantly contributes to the development of rheumatoid arthritis (RA). Activation of the nuclear factor erythroid-2 related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS)-to-NF-κB signaling cascade are important mechanisms regulating osteoclastogenesis; however, whether Nrf2 is involved in RANKL-induced NF-κB activation is controversial. Isoquercitrin, a natural flavonoid compound, has been shown to have Nrf2-dependent antioxidant effects inprevious studies. We sought to verify whether isoquercitrin could modulate RANKL-induced NF-κB activation by activating Nrf2, thereby affecting osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin ring staining and resorption pit assay suggested that isoquercitrin significantly inhibited osteoclastogenesis and osteolytic function. Mitosox staining showed that RANKL-induced ROS generation was significantly inhibited by isoquercitrin from day 3 of the osteoclast differentiation cycle. Quantitative real-time PCR, Western blot, and immunofluorescence indicated that isoquercitrin activated the Nrf2 signaling pathway and inhibited NF-κB expression. And when we used the Nrf2-specific inhibitor ML385, the inhibition of NF-κB by isoquercitrin disappeared. Moreover, we found that Nrf2 is not uninvolved in RANKL-induced NF-κB activation and may be related to the timing of ROS regulation. When we limited isoquercitrin administration to 2 days, Nrf2 remained activated and the inhibition of NF-κB disappeared. In vivo experiments suggested that isoquercitrin attenuated RA modeling-induced bone loss. Overall, isoquercitrin-activated Nrf2 blocked the RANKL-induced ROS-to-NF-κB signaling cascade response, thereby inhibiting osteoclastogenesis and bone loss. These findings provide new ideas for the treatment of RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background/purpose: Headaches are among the most common complaints requiring medical care, and annual expenditures for this condition are estimated to be 14 billion US dollars. The International Headache Society (IHS) describes cervicogenic headache (CGH) as a secondary type of headache emanating from the cervical spine which may be referred to one or more regions of the head and/or face. Mechanical Diagnosis and Therapy (MDT) is an approach shown to be effective in the management of spinal musculoskeletal disorders; however, there is limited evidence as to its efficacy in the management of CGH. The purpose of this case series was to examine the MDT approach in the assessment, classification, and management of a sample of patients experiencing cervicogenic headache., Case Description: This study was a prospective case series. Following IRB approval, 15 patients meeting the study inclusion criteria were recruited from a hospital-based outpatient physical therapy clinic. All subjects received a physical therapy examination by a Diploma trained MDT clinician which included but was not limited to patient self-report forms and the testing of repeated end range movements. The Numerical Pain Rating Scale (NPRS), Neck Disability Index (NDI), Headache Disability Index (HDI), Yellow Flag Risk Form (YFRF), Cervical Flexion Rotation Test (CFRT), and the Craniocervical Flexion Test (CCFT) were administered at the initial visit, 5th visit, and 10th visit or discharge, whichever occurred first. The NPRS, NDI, and HDI were re-administered at a 3 month follow up. Following the initial examination, patients were classified into the MDT categories of derangement, dysfunction, postural, or 'other' and then received intervention based on directional preference., Outcomes: Fifteen subjects (mean age, 45.9 years; F = 11, M  = 4; symptom duration, 44.3 months; average visits, 8.8) received an examination and intervention and completed follow-up outcome measures. Based on MDT classification criteria, all 15 subjects in this case series were classified as derangements. A non-parametric Friedman test of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation differences among repeated measures was conducted on all outcome measures revealing statistically significant improvements in NPRS ( p  < .01), NDI( p  < .01), and HDI ( p  < .01) scores at visit 10 and 3 month follow up. The mean change scores exceeded the minimal clinical important difference (MCID) for NPRS (4.2), NDI (7.6), and HDI (28.5). CCFT scores improved significantly from the initial examination to visit 5 ( p  < .01) and YFRF scores improved significantly between visits 5 and 10 ( p  < .01)., Discussion/conclusion: The diagnosis of CGH is difficult to determine based on pathoanatomical assessment. This case series suggests that the patient's response to repeated end range movements may indicate a directional preference for manual procedures and exercises which may be used in management of musculoskeletal conditions such as CGH.

Background: Lower extremity salvage in the setting of severe trauma requires the consideration of multiple surgical specialties and treatment algorithms. We hypothesized that time to first ambulation, ambulation without an assistive device, chronic osteomyelitis, and delayed amputation were not affected by the time to soft tissue coverage in Gustilo IIIB and IIIC fractures at our institution., Methods: We evaluated all patients treated for open tibia fractures at our institution from 2007 to 2017. Patients requiring any form of soft tissue coverage to the lower extremity during their initial hospitalization and who had at least 30 days of follow-up from time of hospital discharge were included. Univariable and multivariable analysis was performed for all variables and outcomes of interest., Results: Of 575 patients included, 89 required soft tissue coverage. On multivariable analysis, the time to soft tissue coverage, length of negative pressure wound therapy treatment, and number of wound washouts were not found to be associated with development of chronic osteomyelitis, decreased 90-day return to any ambulation, decreased 180-day return to ambulation without assistive device, or delayed amputation., Conclusions: Time to soft tissue coverage in open tibia fractures did not affect time to first ambulation, ambulation without an assistive device, chronic osteomyelitis, or delayed amputation in this cohort. It remains difficult to definitively prove that time to soft tissue coverage meaningfully impacts lower extremity outcomes., Competing Interests: Disclosures: The authors disclosed no conflicts of interest., (© 2022, HMP Global. All rights reserved. Reproduction in whole or in part prohibited. Content may not be reproduced in any form without written permission. Rights, Permission, Reprint, and Translation information is available at www.hmpglobal.com.)

Objective: To study the protective effects of resveratrol (RSV) on cardiac function in rats with high altitude hypobaric hypoxia and its mechanisms. Methods: Thirty-six rats were randomly divided into control group, hypobaric hypoxia group (HH) and hypobaric hypoxia + RSV group (HH+RSV) according to the random number, 12 rats in each group. Rats in the HH and HH+RSV groups were subjected to chronic long-term high altitude hypobaric hypoxia intervention for 8 weeks in a hypobaric chamber at a simulated altitude of 6 000 m for 20 h / d. The rats of HH + RSV were fed with RSV at a dose of 400 mg/(kg·d). The rats were tested once a week for body weight and twice a week for food intake. Before execution, the rats were tested by blood cell analyzer for routine blood parameters and echocardiogram for cardiac function parameters in each group. The routine blood indexes of each group were measured by blood cell analyzer, the cardiac function indexes of each group were measured by echocardiography, myocardial hypertrophy was evaluated by HE staining, myocardial tissue reactive oxygen levels were evaluated by dihydroethidium (DHE) staining. Oxidative stress was evaluated by serum and myocardial tissue total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD) and malondialdehyde (MDA) content. Results: Compared with the C group, the body mass and food intake of rats were decreased significantly ( P ＜0.05) in HH group, while compared with the C group, RSV had no significant effects on the body mass and food intake of rats in the HH+RSV group ( P ＞0.05). Compared with the C group, the levels of erythrocytes and hemoglobin of rats in the HH group were increased significantly ( P ＜0.05), while the platelet concentration was decreased significantly( P ＜0.05); compared with the HH group, the erythrocyte and hemoglobin levels were decreased significantly ( P ＜0.05) and platelet concentration was increased significantly( P ＜0.05) in rats of the HH+RSV group. Compared with the C group, the cardiac coefficient, myocardial fiber diameter and thickness were significantly increased in the HH group ( P ＜0.05); compared with the HH group, the cardiac coefficient and myocardial fiber thickness were significantly decreased in the HH+RSV group ( P ＜0.05). Echocardiographic analysis showed a significant increase in ventricular wall thickness ( P ＜0.05) and a significant decrease in ejection fraction and cardiac output ( P ＜0.05) in the HH group compared with the C group, and a significant decrease in ventricular wall thickness and a significant improvement in cardiac function ( P ＜0.05) in the HH+RSV group compared with the HH group. The results of DHE staining showed that myocardial tissue reactive oxygen levels were increased significantly in the HH group compared with the C group ( P ＜0.05); myocardial tissue reactive oxygen levels were significantly restored in the HH+RSV group compared with the HH group ( P ＜0.05). The oxidative/antioxidant results showed that the serum and myocardial T-AOC and SOD activities were decreased significantly ( P ＜0.05) and the MDA level was increased significantly ( P ＜0.05) in the HH group compared with the C group; the serum and myocardial T-AOC and SOD activities were increased significantly ( P ＜0.05) and the MDA level was decreased significantly( P ＜0.05) in the HH+RSV group compared with the HH group. Conclusion: Long-term plateau hypobaric hypoxia exposure leads to myocardial hypertrophy and reduced cardiac function in rats. Resveratrol intervention significantly improves myocardial hypertrophy and cardiac function in rats caused by altitude hypobaric hypoxia exposure, which is closely related to reducing of reactive oxygen species and improving myocardial oxidative stress levels.

Objective: A gradient stress model of PC12 cells induced by corticosterone was established to provide a basis for the evaluation and regulation of cell stress. Methods: The effect of corticosterone on cell viability was observed by measuring PC12 cell viability at different concentrations of corticosterone (0~1 000 μmol/L) after different intervention times (8~48 h) to screen the cell models for optimal intervention conditions. Key stress indicators (MDA, SOD, NADH, LDH) were measured spectrophotometrically and microscopically to evaluate the models. Results: When the concentration of corticosterone was below 200 μmol/L and the intervention time was 12 h, the cell viability was below half inactivation rate, which could reduce the confounding factors due to the decrease of cell viability in each group. Compared with the blank control group, corticosterone increased the levels of MDA, NADH and LDH,and decreased the levels of SOD in the model group in a concentration-dependent manner ( P ＜0.01), which was consistent with the construction of the gradient stress model. Conclusion: A gradient stress injury model of PC12 cells was successfully established, with intervention concentrations of 0 μmol/L, 25 μmol/L, 50 μmol/L, 100 μmol/L, 150 μmol/L and 200 μmol/L corticosterone at an intervention time of 12 h. The degree of stress injury of the cell model was increased gradually, which could be used as a basis and object for conducting cell stress injury assessment and regulation experiments.

Background: Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. It is the result of a joint effect of lower extremities vascular lesions, neuropathy, and infection, which require amputation and even threaten the life of the patient. At present, the conventional treatment for DFU includes infection control, wound care, wound reduction, reduction of foot pressure, use of dressings that are beneficial to wound surface healing, etc, but the effectiveness is not satisfactory. Recombinant human growth hormone and alginate dressing have been used in clinical, but there is lack of the relevant evidence of its effectiveness and safety, so this study evaluates the clinical effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of DFU by systematic evaluation, the purpose is to provide a theoretical basis for the treatment of diabetic foot ulcer., Methods: This study mainly retrieves the randomized controlled trial of recombinant human growth hormone combined alginate dressing in the treatment of DFU in 7 electronic databases, such as PubMed, EMbase, Cochrane Library, SinoMed, CNKI, WANGFANG database, and VIP database. All the retrieval dates of database are from the establishment of the database until May 31, 2020. At the same time, searching the related degree papers, conference papers, and other gray literature by manual. The original literature data are independently screened and extracted by 2 researchers on the basis of inclusion and exclusion criteria and literature information sheets, and cross-checked and resolved through group discussions and consultations when there are differences of the opinion. Assessing the methodological quality of inclusion in the study based on the "Bias Risk Assessment Form" of the Cochrane Collaboration Network. Using the software of RevMan 5.3.3 and STATA 13.0 for statistical analysis., Results: This study compares the main and secondary outcome indicators by systematic evaluation and it will provide strong evidence of recombinant human growth hormone combined alginate dressing in the treatment of DFU., Ethics and Dissemination: All data in this study are obtained through the web database and do not involve humans, so ethical approval is not suitable for this study., Osf Registration Number: DOI 10.17605/OSF.IO/W6P24., Conclusion: This study will give positive conclusions about the effectiveness and safety of recombinant human growth hormone combined alginate dressing in the treatment of DFU., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To develop a new congenital cleft palate model suitable for the evaluation of cleft palate surgery and other related treatments. Methods: Ten New Zealand female rabbits (aged 40 weeks, 4.5-5.0 kg) were selected. The next day after mating with male rabbits of the same strain was regarded as the day 1 of gestation (GD1). Ten pregnant rabbits were enrolled with intramuscular injection 1.0 mg dosage of dexamethasone once a day from GD13 to GD16. The caesarean section was performed to obtain the newborn rabbits on GD31 for each pregnant rabbit. Then the rates of the survival and cleft palate rabbits were calculated. The rabbits were divided into two groups according to the method of random number table (10 non-cleft palate rabbits as the control group and 10 cleft palate rabbits as the experimental group). The body weights and physiological behaviors of the rabbits were evaluated and recorded at the age of 1, 2 and 4 weeks respectively after being fed by using standardized gastric tube feeding method. At 4 weeks old, three rabbits in each group were randomly selected for the observation of local anatomy of different layers of the mouth and upper jaw. The anatomical results were photographed for comparative analysis. Results: In this experiment, 48 infants of 10 pregnant rabbits survived under the condition with a survival rate of 66% (48/73), among which the incidence of cleft palate was 60% (29/48). All the rabbits in the control group and the experimental group were able to survive for at least 1 month with stable weight gain. There was no significant difference in weight ( P >0.05) and physiological appearance between the two groups. In cleft palate group, most of fetuses showed complete cleft palate with significant differences in the anatomical structure of the upper jaw compared with the control group including the changes in the morphology of the palatal mucosa, the terminal distribution of the soft palate muscles, and the dysplasia and absence of bone structures along the mid-maxillary line. Conclusions: In this study, it was the first time to successfully establish the dexamethasone-induced congenital cleft palate model in New Zealand rabbits for cleft surgical research.

Objective: To investigate the effects of mitogen-activated protein kinases (MAPKs) inhibitors on glutathione (GSH) metabolism, and to explore the pathway related to GSH metabolism., Methods: BRL rat hepatocytes were treated by c-Jun NH2-terminal kinase (JNK),p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors:SP600125, SB203580 and PD98659, respectively, for 24 h. MTT method was used to measure hepatocytes viability. The content of GSH was determined by high performance liquid chromatography. The protein expressions of JNK and phosphorylated JNK (p-JNK) was tested by Luminex method. Activities of GSH metabolic enzymes were detected by commercial kits., Results: Hepatocytes vitality was inhibited when the concentrations of SP600125, SB203580 and PD98659 were higher than 10 μ mol/L, 20 μ mol/L, and 40 μ mol/L, respectively; SP600125 decreased the content of GSH in hepatocytes, while SB203580 and PD98659 had no effect. SP600125 reduced p-JNK protein expression, and enhanced GSH-Px activity significantly., Conclusions: JNK MAPK pathway takes part in the GSH metabolism in hepatocytes.

Introduction: Plastic surgeons endure years of training yet remain poorly equipped to negotiate first employment contracts. Our aims were to evaluate typical plastic surgeon employment contracts and assess contract comprehensiveness. We sought elements that should be included to better preserve varied interests., Methods: A brief, anonymous, e-mailed survey was sent to California Society of Plastic Surgeons members and responses collected over 2 months. We collected information such as years in practice, geographic area, types of practices and number of surgeons within them, and legal standing of partnerships. We asked whether respondents sought legal assistance and specific elements were elaborated. We asked how content they were with their contracts while allowing commentary., Results: Our survey generated 113 responses. 50.0% of respondents reported being in practice for at least 20 years; 2.68% had been in practice for up to 5 years. 62.5% reported being in private practice and 27.7% reported being in academia. In-state geographic distribution of respondents accounted for 85.6%, whereas 14.4% reported practicing out-of-state.Practice size was diverse, with 41.4% of respondents having worked in a group practice of 3 or more, 27.9% in partnership, and 23.4% in solo practice. For partnerships, 29.9% had made formal legal arrangements, whereas 20.6% had made informal arrangements. 74.5% of respondents did not seek legal assistance.Malpractice coverage varied from 51.6% with claims-made, to 21.7% with tail, to 33.0% with no coverage at all. 63.9% reported having no group disability policy. 26.4% reported annual income of less than US $100,000; 49.1% reported US $101,000 to US $200,000; 17.9% reported US $201,000 to US $300,000; 6.60% reported greater than US $300,000. Using a 5-point scale, 7.69% of respondents reported being "extremely dissatisfied" with their first employment contracts (score of 1), whereas 24.0% were "perfectly happy" (5).Eighty-two respondents offered advice. Common themes included seeking legal counsel; considering eventual solo practice; planning long-term; seeking mentorship; and cautioning against third party interests., Conclusions: New plastic surgeons will find themselves employed by institutions. Seeking attorneys familiar with the profession is advisable. Lack of awareness regarding malpractice options and disability coverage are 2 areas of concern. We reveal critical contract elements that surgeons should negotiate to ensure smooth transition to practice.

Background: Plastic surgery may have traditionally been labelled as a "less essential" service at many academic medical centers in the United States. The purpose of this study is to evaluate the role of the plastic surgery team as a valuable service at an academic medical center., Methods: We performed a 10-year retrospective case review of a single plastic surgeon's case log at 2 academic medical institutions, each with an active plastic surgery training program. Plastic surgical procedures performed in combination with other services and surgical management of complications from nonplastic surgical procedures was evaluated. Plastic surgical procedures performed for all types of reconstruction as a primary service, including breast reconstruction were excluded. The role of the plastic surgery service was evaluated to identify the types of assistance provided, which primary services were involved and what the most common procedures performed were for each service., Results: The type of assistance provided by the plastic surgery service was divided into 2 common categories. The first type involved a concurrent or combined surgical case where the procedure required plastic surgery's participation. The second group included management of complications that occurred on another service, which then required assistance by the plastic surgery team. A total of thirteen primary services were identified as benefitting from involvement with plastic surgery. The most commonly performed reconstructive procedures provided for each service were identified., Conclusions: The plastic surgery team provides invaluable support to other services in a tertiary teaching hospital. Its input allows for more complex surgical procedures to be performed safely and for complications of surgery to be managed successfully. Clearly, plastic surgery plays a critical role at academic medical centers in the United States.

Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab., Case Presentation: A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB) corresponding to 95-96 percentile in lung SCC, i.e., 87.4-91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient's immune system against one or more preexisting tumor-associated antigens (TAAs). One potential TAA candidate is telomerase reverse transcriptase (TERT) in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been used to develop universal cancer vaccine targeting TERT-derived peptides., Conclusions: Nivolumab could quickly reset and sustain host immunity against preexisting TAA(s) in this chemotherapy-refractory lung SCC patient. Further mechanistic studies are needed to characterize the effective immune cells and define the HLA-restricted TAA(s) and the specific T cell receptor clones responsible for the potent antitumor effect, with the aim of developing precision immunotherapy with improved effectiveness and safety.

Background: The purpose of this study was to introduce a comprehensive approach to lower extremity free-tissue transfer and report the clinical outcome that has been achieved with this approach., Methods: The comprehensive approach developed by the author includes patient selection, flap selection, selection of the recipient vessels, flap dissection, flap preparation, microvascular anastomosis, flap inset, immediate postoperative care, intermediate postoperative care, and further follow-up care. Each part of this approach has its own special considerations. In an 8-year period, 28 consecutive lower extremity free-tissue transfers were performed in 28 patients by the author. The clinical outcomes were recorded based on the success of free-tissue transfer, any reoperations related to the revision of microvascular anastomosis, and any partial or total flap loss during an 8-year follow-up., Results: All 28 lower extremity free-tissue transfers were performed successfully. All patients were discharged home once they tolerated dangling. No reoperations were needed for revision of microvascular anastomosis. No total or partial flap loss was encountered. Overall success of free-tissue transfer to the lower extremity in this series was 100%., Conclusions: An ideal outcome of free-tissue transfer to the lower extremity can be accomplished with this comprehensive approach developed by the author. With good surgical judgment, adequate microsurgical skill, step-by-step intraoperative execution, and a protocol-driven clinical practice, the reconstructive surgeon should be able to improve his or her success for free-tissue transfer to the lower extremity.

Reconstruction of the postburn hand remains a challenge for surgeons. For cosmetic and functional requirements, the desired flap should be thin enough to ensure the flexibility of the hand. Conventional perforator flaps serve as a viable option when reconstructing the postburn hand to regain functionality. However, limitations include the discrepancy in tissue thickness and the difficulty with donor site closure. Thus, a preexpanded superthin skin perforator flap is an ideal choice for postburn hand reconstruction, with the trade-off being a longer treatment course (3-4 months), but with results that satisfy both patients and their surgeons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although clinical application of a pre-expanded perforator flap is primarily focused on face and neck reconstructions, such a flap has also been used to reconstruct defects in the trunk, extremities, or hands. With better understanding of the improved blood supply to the flap and the mechanism on the prefabrication of blood supply within the flap, the pre-expanded perforator flap will definitely play a more important role in reconstructive surgery and can be used in selected patients by many plastic surgeons worldwide with good reconstructive and cosmetic outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pre-expanded perforator flaps, a combination of tissue expansion with perforator flaps, are emerging as another landmark of plastic surgery. This flap inherits the characteristics of both perforator flaps and expanded flaps, making it a highly versatile option in reconstructive surgery. However, the definition of the pre-expanded perforator flap and the impact of pre-expansion on the superficial angio-architecture remain controversial. In this article, the authors review current concepts including the mechanism of expansion and the resultant changes in the angio-architecture. The authors also review the previous studies and classifications of pre-expanded perforator flaps., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients with severe postburn scar contractures underwent reconstruction of skin defects after scar excision with pre-expanded super-thin skin perforator flaps supplied primarily by perforators via the "bridging effect" from the branches of the adjacent arteries as 2-stage procedures. Pre-expansion is an innovative technique and may improve the anastomoses between subdermal vascular plexuses and extend the supplying area of these vessels to the flap. Such a flap becomes super thin, but with a prefabricated blood supply it can be used for reconstruction of skin defects of the face, neck, or other body part with improved functional and cosmetic outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pre-expanded perforator flaps have several advantages over their traditional counterparts owing to the thin, more pliable nature, larger size, and minimum morbidity of the donor site. Recently, plastic surgeons have begun to use pre-expanded perforator flaps to reconstruct defects of almost the entire body, including the cervicofacial region, axilla, trunk, and extremities resulting from scar, congenital melanocytic nevi, hemangiomas, and neurofibromas. Such a versatile flap is especially appropriate for face and neck resurfacing, which requires more optimal functional and cosmetic outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Because the course and territory of perforators are different in each region, careful preoperative planning to identify the proper perforators can be critical to ensure a successful dissection of a freestyle pedicled perforator flap. In this study, our first experience for preoperative perforator mapping of a freestyle pedicled perforator flap using multidetector row computed tomography (MD-CT) angiography is presented., Methods: Twelve patients were planned to undergo various soft-tissue reconstructions with freestyle pedicled perforator flaps. They were evaluated with preoperative MD-CT angiography. The OsiriX for mac software was used to process the data obtained from MD-CT angiography. The available images from MD-CT angiography were analyzed to determine where the proper perforators were located for preoperative planning of a freestyle pedicled perforator flap. Through the MD-CT angiography, the optimal perforators were mapped and a reliable flap design could be made so that the flap was elevated more safely and perfectly to cover an adjacent soft-tissue defect., Results: In all 12 patients, each flap was elevated successfully based on the perforators mapped preoperatively with MD-CT angiography. A total of 27 perforators (1-3 perforators per flap) were identified by MD-CT angiography in 12 patients and later confirmed during the flap dissection (sensitivity, 100%)., Conclusions: The MD-CT angiography can be a new but very effective imaging modality for preoperative planning of a freestyle pedicled perforator flap surgery. It allows surgeons to accurately select the most appropriate perforators with the shortest intramuscular or suprafascial course preoperatively leading to safer and easier flap dissection.

Manduca sexta, known as the tobacco hornworm or Carolina sphinx moth, is a lepidopteran insect that is used extensively as a model system for research in insect biochemistry, physiology, neurobiology, development, and immunity. One important benefit of this species as an experimental model is its extremely large size, reaching more than 10 g in the larval stage. M. sexta larvae feed on solanaceous plants and thus must tolerate a substantial challenge from plant allelochemicals, including nicotine. We report the sequence and annotation of the M. sexta genome, and a survey of gene expression in various tissues and developmental stages. The Msex&#95;1.0 genome assembly resulted in a total genome size of 419.4 Mbp. Repetitive sequences accounted for 25.8% of the assembled genome. The official gene set is comprised of 15,451 protein-coding genes, of which 2498 were manually curated. Extensive RNA-seq data from many tissues and developmental stages were used to improve gene models and for insights into gene expression patterns. Genome wide synteny analysis indicated a high level of macrosynteny in the Lepidoptera. Annotation and analyses were carried out for gene families involved in a wide spectrum of biological processes, including apoptosis, vacuole sorting, growth and development, structures of exoskeleton, egg shells, and muscle, vision, chemosensation, ion channels, signal transduction, neuropeptide signaling, neurotransmitter synthesis and transport, nicotine tolerance, lipid metabolism, and immunity. This genome sequence, annotation, and analysis provide an important new resource from a well-studied model insect species and will facilitate further biochemical and mechanistic experimental studies of many biological systems in insects., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Although more fat grafting procedures have been performed by plastic surgeons with the primary goal to restore soft tissue loss, the actual mechanism on how fat graft survives remains less completely understood. An established old theory on fat graft survival is still based on the cell survival theory proposed by Peer in the early 1950s. On the basis of his preliminary experimental study, he proposed that the mechanism of fat graft survival is based on established early blood circulation through anastomosis of the fat graft and host blood vessels. Recently, several investigators have demonstrated new concepts of the fat graft survival: One further advanced the old Peer cell survival theory and another based on new discovery and understanding of adipose-derived stem cells. This article serves as a scientific review on how fat graft survives after in vivo transplantation based on a number of well-conducted experimental studies. Both the graft survival and graft replacement theories on how fat graft survives are true based on the previously mentioned well-conducted experimental studies. Each theory may play a role in fat graft survival. It is possible that graft survival may be more dominant in some patients but the graft replacement may be more dominant in other patients.

Objective: Based on our previous animal study, we applied the "bridging effect" to the neighboring axial flap through preexpansion and prefabrication of a skin perforator flap as a new method to reconstruct a large skin defect after release of severe neck burn scar contracture., Methods: Twelve patients suffering from severe post-burn cervical contractures underwent reconstruction of large skin defects after surgical release of severe scar contractures with preexpanded and prefabricated super-thin skin perforator flaps supplied primarily by a number of perforators via the "bridging effect" from the branches of the adjacent arteries as 2-stage procedures. During the first-stage operation, 2 tissue expanders were placed accordingly, and this was followed by a subsequent second-stage procedure where an expanded super-thin skin perforator flap was transposed to reconstruct a large neck skin defect. Follow-up was between 6 months and 3 years in this series., Results: All super-thin skin perforator flaps survived in this series with primary healing except one with a distal flap necrosis that was treated with a subsequent skin graft. All patients have had a good contour with improved range of motion in the neck., Conclusions: The preexpansion and prefabrication of a super-thin skin perforator flap can possibly improve the anastomoses between neighboring subdermal vascular plexuses and extend the supplying area of these vessels to the flap. This method may provide a favorable super-thin skin flap that can be used for reconstruction of large neck defects after release of post-burn cervical scar contracture as demonstrated in this case series.

Autologous fat grafting is an exciting part of plastic and reconstructive surgery. Fat serves as a filler and its role in tissue regeneration will likely play a more important role in our specialty. As we learn more about the basic science of fat grafting and the standardized techniques and instruments used for fat grafting, this procedure alone or in conjunction with invasive procedures may be able to replace many operations that we perform currently. Its minimally invasive nature will benefit greatly our cosmetic and reconstructive patients, and may even achieve better clinical outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Conduit necrosis is a rare but potentially devastating complication of oesophageal surgery and the subsequent reversal of oesophageal discontinuity can be challenging. An option for both cervical-oesophageal reconstruction and neck wound closure has been limited and less successful. We report a patient with colon conduit necrosis and cervical-oesophageal discontinuity whose cervial oesophagus was successfully reconstructed with a single-stage pedicled pectoralis major myocutaneous flap and neck wound closure., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Lower extremity reconstructions may be pursued by adhering to established algorithms primarily based on the area of injury and the extent of missing tissue and wound. Certain flaps--either local or free--have been relied on as workhorse flaps for soft-tissue reconstruction of the lower extremity. However, when these flaps are unavailable or contraindicated, alternative options can be considered for reconstruction of relatively small wounds in the lower extremity., Methods: We report 2 cases of complex lower extremity wounds that were the result of complications from orthopedic procedures after traumatic injuries. In case 1, an exposed Achilles tendon (7×3 cm) after wound infection and breakdown after orthopedic fixation was performed using a distally based peroneal brevis muscle flap with split thickness skin grafting. The same patient also had a previous free anterolateral thigh flap for the coverage of his medial tibial wound in the distal third of the leg with success. In case 2, a middle lateral leg wound (5×3 cm) with exposed tibia as a result of hematoma and wound breakdown after orthopedic debridement was reconstructed with a distally based tibialis anterior muscle flap with split thickness skin grafting., Results: Full soft tissue coverage of the defects was achieved using these distally based local muscle flaps. There was complete healing of each complex wound in the lower extremity without complications, thus a microvascular free flap reconstruction for those patients was avoided. Aesthetic appearance of the reconstructions was closely matched to the native skin. Functional status was acceptable over long-term follow-up in both patients., Conclusions: For complex lower extremity wounds, less commonly used local muscle flaps that are distally based may successfully reconstruct certain relatively small defects in the lower extremity. Knowledge of these flaps and illustration of their success allow the reconstructive surgeon to confidently add them to the reconstructive armamentarium.

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats., Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits., Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.

This article first discusses some fundamentals of cryobiology and challenges for cell and tissue cryopreservation. Then, the results of cryopreservation of adipose cells and tissues, including adipose-derived stem cells, in the last decade are reviewed. In addition, from the viewpoint of cryobiology, some desired future work in fat cryopreservation is proposed that would benefit the optimization, standardization, and better application of such techniques., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fat grafting still remains technique dependent with possible less favorable long-term results because there are no standardized techniques used by the surgeon to perform the procedure. In this article, the authors have tried to standardize the techniques for fat grafting as first proposed and popularized by Coleman. These techniques, supported by the most recent scientific studies and understandings of clinical course following autologous fat transplantation, emphasize proper fat harvesting, processing, and placement so that a predictable long-lasting result can be achieved., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history., Competing Interests: The authors have declared that no competing interests exist.

Breast reduction is a common procedure performed by plastic surgeons for functional or cosmetic improvement of the breast. However, final outcome can be less satisfactory to patients in terms of the size, shape, symmetry, scarring, or wound healing complications. However, good to excellent outcome after breast reduction can be accomplished by plastic surgeons once they have mastered their technique. The medial pedicle vertical breast reduction has been popularized recently. However, the technique is technically more complex, and the results have been less inconsistent with a learning curve. In addition, the technique has been criticized for a residual deformity in the lower pole of the breast and resulted in a high revision rate. In this article, key components for the medial pedicle vertical breast reduction including patient selection and technical refinements are discussed in details. The author describes his philosophy in patient selection, preoperative and intraoperative markings of the breast, and step-by-step surgical procedures with several technical refinements for the medical pedicle vertical breast reduction. In addition, the pearls for achieving an optimal outcome of such a breast reduction are also discussed.

Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community., (© 2014 Chen et al.; Published by Cold Spring Harbor Laboratory Press.)

Introduction: The free anterolateral thigh (ALT) flap has been used successfully for various soft tissue reconstructions. However, the drawback of this flap has been the difficulty associated with finding consistent perforators due to the variable anatomy. In this study, the value of color duplex imaging for reliably identifying the perforators of the flap was investigated., Methods: Nineteen patients of various ethnicities and sex (17 men, 2 women) were studied and were planned to undergo reconstruction with free ALT flaps. They were evaluated using color duplex in the operating room before flap elevation. This imaging was performed in less than 20 minutes by a vascular technologist under the guidance of the surgeon on both thigh donor sites., Results: All imaged major perforators were identified during flap elevation (sensitivity, 100%) and all the flaps were successfully elevated based on 1 or 2 identified perforators. There were no unexpected operative plan changes. The perforators were mapped, allowing for easy dissection secondary to the ability to evaluate the perforators for their size and location as well as potential intramuscular course. Also, the surgeons were able to select the side that was likely to give the highest probability of success., Conclusions: The color duplex scan is a useful imaging modality for planning and performing free ALT flap. It enables surgeons to improve efficiency in the operating room and overall outcomes, as well as shortens the learning curve when first performing these highly variable flaps. The close working relationship between the vascular technologist and the surgeon may be the key to its success.

Background: With growing contribution to plastic surgery by our international colleagues, one may be wondering about what US plastic surgeons have learned from them. The purpose of this study was to evaluate a single surgeon's experience to identify any specific areas of plastic surgery that one has learned substantially from our international colleagues., Methods: All plastic surgical procedures performed by a single US plastic surgeon at an academic medical center with an active plastic surgery residency training program during the past 10 years were reviewed. More frequently performed procedures by the author were identified. In each identified procedure, critical references used by the author were examined to find out whether these references were from domestic or international sources., Results: More frequently performed procedures by the author were (1) free anterolateral thigh perforator flap and free-style free flap, (2) deep inferior epigastric perforator flap breast reconstruction, (3) implant-based breast reconstruction, (4) oncoplastic breast reduction or mastopexy for breast reconstruction, (5) vertical scar breast reduction, and (6) fat grafting for correction of contour deformity after breast reconstruction. Much more innovative procedures that the author had learned after his residency were published primarily by our international colleagues., Conclusions: The author has learned substantially from our international colleagues because many new procedures may be either first described by them or they have more extensive clinical experience. It is important to fully appreciate the significance of international scientific exchange in plastic surgery and its impact on a US plastic surgeon's clinical practice.

Introduction: The free anterolateral thigh (ALT) skin perforator flap has gained enormous popularity as a free skin perforator flap. Currently being used for various reconstructions primarily in Asia, its routine application for soft-tissue reconstruction of the lower extremity remains unknown in the United States. The purpose of the present study was to review the current trend of flap selection for soft tissue reconstruction of the lower extremity., Methods: We performed a retrospective review of a single-surgeon case log between 2007 and 2011 in a tertiary academic medical center. Inclusion criteria were patients who underwent free tissue transfer for lower extremity reconstruction regardless of sex or age. Exclusion criteria were limited to patients with a body mass index greater than 35 kg/m. A total of 20 patients underwent reconstruction with a free tissue transfer for soft tissue coverage of the lower extremity wound were identified., Results: Fourteen free ALT and 6 free muscle flap reconstructions were performed over a 4-year period. Good reconstructive outcomes resulting in reliable soft tissue coverage were achieved in all patients. It was noted that more ALT flaps were used in the last 2 years and less muscle flaps (0/8 vs 6/12, P = 0.042) when compared with the years prior., Conclusions: Although technically more challenging to perform, the free ALT flap has recently been used significantly more for lower extremity reconstruction because of its minimal donor-site morbidity, reliable coverage, and improved contour. This represents a paradigm shift in flap selection that is being highlighted as surgical proficiency in flap dissection technique improves.

Introduction: Major facial trauma injuries often require complex repair. Traditionally, the reconstruction of such injuries has primarily utilized only free tissue transfer. However, the advent of newer, contemporary procedures may lead to potential reconstructive improvement through the use of complementary procedures after free flap reconstruction., Methods: An 18-year-old male patient suffered a major left facial degloving injury resulting in soft-tissue defect with exposed zygoma, and parietal bone. Multiple operations were undertaken in a staged manner for reconstruction. A state-of-the-art free anterolateral thigh (ALT) perforator flap and Medpor implant reconstruction of the midface were initially performed, followed by flap debulking, lateral canthopexy, midface lift with redo canthopexy, scalp tissue expansion for hairline reconstruction, and epidermal skin grafting for optimal skin color matching., Results: Over a follow-up period of 2 years, a good and impressive reconstructive result was achieved through the use of multiple contemporary reconstructive procedures following an excellent free ALT flap reconstruction., Conclusions: Multiple staged reconstructions are essential in producing an optimal outcome in this complex facial injury that would likely not have been produced through a 1-stage traditional free flap reconstruction. Utilizing multiple, sequential contemporary surgeries may substantially improve outcome through the enhancement and refinement of results based on possibly the best initial soft-tissue reconstruction.

Introduction: Free tissue transfer to the areas around the knee or hip can be difficult because there are limited options for reliable recipient vessels, but extended vein grafts may decrease the chance for success. The purpose of this study was to describe our experience with creating a proper recipient vessel for free flap reconstructions in these areas using the descending branch of the lateral circumflex femoral vessels in the thigh., Methods: Two patients underwent free flap reconstruction of a complex knee wound after orthopedic trauma and a complex hip wound after arthroplasty. A contralateral anterior lateral thigh perforator flap and a latissimus dorsi flap were used to close the wounds, respectively. Dissection was carried between the rectus femoris and vastus lateralis and a recipient vessel was created and placed in more desirable location adjacent to the defect for microvascular anastomoses., Results: A long 12-cm recipient vessel measuring 1.5 to 2.5 cm in diameter for both artery and vein was dissected and placed in an area adjacent to the defect for a straightforward microvascular microanastomosis. Both patients had successful free tissue reconstructions with uneventful postoperative recoveries. The flaps remained viable and the wounds healed with follow-up, revealing reliable soft tissue and good contour in the reconstructed areas., Conclusions: The descending branch of the lateral circumflex femoral vessels can be dissected out and serve as a recipient vessel after being placed adjacent to the defect for free tissue transfer to the difficult areas of the lower extremity. Creation of such a recipient vessel would avoid using vein grafts and ease free flap reconstruction to those difficult reconstructive areas.

Background: Even though fat grafting has become widely used by plastic surgeons, most surgeons choose their method of fat grafting based almost entirely on anecdotal evidence. As more and more scientific studies appear in the literature, we now may have more objective, scientific evidence to support the use of specific techniques., Methods: The author critically reviewed all studies related to fat grafting research in the last 20 years in the English literature. To better summarize the findings of the studies, the fat grafting procedure was arbitrarily divided into 4 essential parts to determine the best donor sites and how the fat grafts should be harvested, processed, and placed., Results: While most studies show no difference in the viability of fat grafts harvested from different donor sites, one study shows that more adipose-derived stem cells (ADSCs) are found within the fat grafts harvested from the lower abdomen or inner thigh. Fat grafts harvested with syringe aspiration and processed with centrifugation at 1200 g for 3 min clearly have better viability. In addition, viable adipocytes and ADSCs as well as growth factors can be concentrated within the fat grafts after proper centrifugation. The studies also reinforce the principle that fat grafts, once placed, should have a maximal amount of contact with the vascularized tissue in the recipient site for better survival., Conclusions: Most scientific studies in fat grafting research support a more rationalized technique that should be selected by surgeons for fat grafting. The technique includes proper selection of donor sites, proper harvest and process of fat grafts, and proper placement of fat grafts., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Gynecomastia is a common disorder observed in male plastic surgery patients. Treatment options may include observation, surgical excision, or liposuction techniques. Congenital herniated nipple is a more rare condition, especially in male patients. We present the case of a 12-year-old boy with bilateral gynecomastia and herniated nipple-areolar complexes., Methods: A staged repair was undertaken in this patient with grade 2 gynecomastia. The first operation was ultrasonic liposuction bilaterally, yielding 200 mL of aspirate from the left and 400 mL on the right, to correct the gynecomastia. The second procedure, performed 6 months later, was a bilateral periareolar mastopexy to repair the herniated nipple-areolar complexes., Results: The result of the first procedure was flattened and symmetrical breast tissue bilaterally, essentially a correction of the gynecomastia. The herniated nipples were still present, however. Bilateral periareolar mastopexies were then performed with resulting reduction of the herniations. There were no complications with either procedure, and a good cosmetic result was achieved., Conclusions: A staged surgical approach was successful in correcting both conditions with an excellent aesthetic result and the advantage of decreased risk for nipple complications.