Gynecomastia Surgery Patient Education: An Information Quality Assessment of YouTube Videos.

BACKGROUND: YouTube is a platform for many topics, including plastic surgery. Previous studies have shown poor educational value in YouTube videos of plastic surgery procedures. The purpose of this study was to evaluate the quality and accuracy of YouTube videos concerning gynecomastia surgery (GS). METHODS: The phrases "gynecomastia surgery" (GS) and "man boobs surgery" (MB) were queried on YouTube. The first 50 videos for each search term were examined. The videos were rated using our novel Gynecomastia Surgery Specific Score to measure gynecomastia-specific information, the Patient Education Materials Assessment Tool (PEMAT) to measure understandability and actionability, and the Global Quality Scale to measure general quality. RESULTS: The most common upload source was a board-certified plastic surgeon (35%), and content category was surgery techniques and consultations (51%). Average scores for the Global Quality Scale (x̄ = 2.25), Gynecomastia Surgery Specific Score (x̄ = 3.50), and PEMAT Actionability (x̄ = 44.8%) were low, whereas PEMAT Understandability (x̄ = 77.4%) was moderate to high. There was no difference in all scoring modalities between the GS and MB groups. Internationally uploaded MB videos tended to originate from Asian countries, whereas GS videos tended to originate from non-US Western countries. Patient uploaders had higher PEMAT Actionability scores than plastic surgeon uploaders. CONCLUSIONS: The quality and amount of gynecomastia-specific information in GS videos on YouTube are low and contain few practical, take-home points for patients. However, understandability is adequate. Plastic surgeons and professional societies should strive to create high-quality medical media on platforms such as YouTube.

Selective Thumb Carpometacarpal Joint Denervation Versus Trapeziectomy and Ligament Reconstruction With Tendon Interposition for Painful Arthritis: A Prospective Study With 2 Years of Follow-Up.

PURPOSE: Thumb carpometacarpal (CMC) joint denervation is a relatively novel method for the management of osteoarthritis-associated pain by selective transection of articular nerve branches of the CMC joint. This study compared functional/patient-reported outcomes after CMC denervation with those after trapeziectomy and ligament reconstruction with tendon interposition (T + LRTI) over a 2-year follow-up period. We hypothesized that the outcomes of denervation and T + LRTI would be similar over the course of the study and at the final 2-year follow-up. METHODS: Adults with Eaton stage 2-4 disease, no evidence of CMC subluxation, and no history of thumb injury/surgery were included. Pain scores, brief Michigan Hand Questionnaire (bMHQ), Kapandji score, 2-point discrimination, and grip/key/3-point pinch strength were measured at 3-, 6-, 12-, and 24-months after surgery. On average, T + LRTI patients underwent 7 weeks of splinting, with release to full activity at 3 months; denervation patients were placed in a soft postoperative dressing for 2 weeks, with release to full activity as tolerated at 3 weeks. RESULTS: Thirty-three denervation and 20 T + LRTI patients were included. Preoperative characteristics were similar between both groups. Two denervation patients underwent secondary T + LRTI during the study period; one denervation patient underwent fat grafting to the CMC joint at an outside institution. Data prior to secondary surgeries were included in the analysis. The average tourniquet times (minutes) for denervation and T + LRTI were 43.5 ± 11.8 and 82.7 ± 14.2 minutes, respectively. For denervation and T + LRTI, the postoperative bMHQ scores were significantly higher than those at baseline at all time points. No significant differences were found between both groups for bMHQ, sensation, or strength measures. CONCLUSIONS: Carpometacarpal denervation is well tolerated, with shorter tourniquet times and faster return to full activity than T + LRTI. For the study cohort, the conversion rate to T + LRTI at 2 years was 9%. Both procedures demonstrated durable improvement in bMHQ compared with the preoperative state with similar long-term outcomes over 2 years of follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Case Report: Nyctalopia Due to Severe Liver Cirrhosis-induced Vitamin A Deficiency.

SIGNIFICANCE: Vitamin A is a micronutrient critical for retinal function. Patients with a deficiency may notice a progressive decline in night vision as rod photoreceptors become unable to regenerate rhodopsin. Although uncommon in developed nations, vitamin A deficiency should be considered in symptomatic patients with chronic, severe liver disease. PURPOSE: This report presents a rare case of night blindness secondary to poor vitamin A metabolism due to severe liver cirrhosis. CASE REPORT: A 62-year-old White woman presented with progressively worsening vision in dim lighting over the past 6 to 8 months. She was asymptomatic in daylight but "blind in the dark" to the extent that she was afraid to go outside at night. She had no personal or family history of night blindness or retinal disorders. Ocular health was unremarkable with dilation. Given her medical history of severe nonalcoholic liver cirrhosis, malabsorption of vitamin A was suspected and subsequently confirmed by the very low vitamin A level in her serum analysis. The patient was sent to endocrinology for evaluation, and appropriate repletion therapy was implemented. Subjective improvement in symptoms, along with better performance on visual field testing, was noted after initiating oral vitamin A supplementation for 5 months. CONCLUSIONS: Although vitamin A deficiency is a relatively rare disorder in the United States, it should be suspected in patients with severe liver disease or other conditions causing malabsorption who experience a loss of night vision.

The Efficacy of Schwann-Like Differentiated Muscle-Derived Stem Cells in Treating Rodent Upper Extremity Peripheral Nerve Injury.

BACKGROUND: There is a pressing need to identify alternative mesenchymal stem cell sources for Schwann cell cellular replacement therapy, to improve peripheral nerve regeneration. This study assessed the efficacy of Schwann cell-like cells (induced muscle-derived stem cells) differentiated from muscle-derived stem cells (MDSCs) in augmenting nerve regeneration and improving muscle function after nerve trauma. METHODS: The Schwann cell-like nature of induced MDSCs was characterized in vitro using immunofluorescence, flow cytometry, microarray, and reverse-transcription polymerase chain reaction. In vivo, four groups (n = 5 per group) of rats with median nerve injuries were examined: group 1 animals were treated with intraneural phosphate-buffered saline after cold and crush axonotmesis (negative control); group 2 animals were no-injury controls; group 3 animals were treated with intraneural green fluorescent protein-positive MDSCs; and group 4 animals were treated with green fluorescent protein-positive induced MDSCs. All animals underwent weekly upper extremity functional testing. Rats were euthanized 5 weeks after treatment. The median nerve and extrinsic finger flexors were harvested for nerve histomorphometry, myelination, muscle weight, and atrophy analyses. RESULTS: In vitro, induced MDSCs recapitulated native Schwann cell gene expression patterns and up-regulated pathways involved in neuronal growth/signaling. In vivo, green fluorescent protein-positive induced MDSCs remained stably transformed 5 weeks after injection. Induced MDSC therapy decreased muscle atrophy after median nerve injury (p = 0.0143). Induced MDSC- and MDSC-treated animals demonstrated greater functional muscle recovery when compared to untreated controls (hand grip after induced MDSC treatment: group 1, 0.91 N; group 4, 3.38 N); p < 0.0001) at 5 weeks after treatment. This may demonstrate the potential beneficial effects of MDSC therapy, regardless of differentiation stage. CONCLUSION: Both MDSCs and induced MDSCs decrease denervation muscle atrophy and improve subsequent functional outcomes after upper extremity nerve trauma in rodents.

What Is the Impact of Postoperative Antibiotic Prophylaxis on Tissue Expander Infection Rates in Pediatric Patients?

BACKGROUND: Tissue expansion in the pediatric population can be complicated by high rates of infection and extrusion. The aim of this study was to examine the impact of postoperative antibiotic prophylaxis on infectious complications. METHODS: A retrospective study of all pediatric patients who underwent tissue expander insertion at a children's hospital over a 12-year period was performed. Predictor variables included age, sex, race, indication, anatomical location, number of expanders inserted, serial expansion, history of infection or extrusion, and postoperative antibiotics. Outcome variables included infection and extrusion. Bivariate and multivariate analyses were performed to identify factors associated with infection and/or extrusion. RESULTS: A total of 180 patients who underwent 317 operations for tissue expander insertion were included in this study. Postoperative infection and/or extrusion occurred after 73 operations (23 percent). Postoperative prophylactic antibiotics were prescribed after 232 operations (75 percent), and only perioperative (≤24 hours) antibiotics were administered in 85 cases (25 percent). There were no significant differences in the rate of infection (12.1 percent versus 8.9 percent; p = 0.46), extrusion (16.8 percent versus 17.7 percent; p = 0.88), or infection and/or extrusion (23.7 percent versus 24.1 percent; p = 0.95) between these two groups. Multivariate analysis revealed that postoperative antibiotics did not have a significant association with infection and/or extrusion (OR, 0.84; 95 percent CI, 0.44 to 1.63; p = 0.61). CONCLUSIONS: The rates of infection/extrusion were similar between pediatric patients who received only perioperative antibiotics (≤24 hours) and those who were prescribed a course of postoperative antibiotics. Based on these results, a course of postoperative prophylactic antibiotics may be unnecessary after insertion of tissue expanders in pediatric patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Case Report: Unilateral Cranial Nerve IV Palsy Secondary to Trochlear Schwannoma.

SIGNIFICANCE: Cranial nerve IV palsy is the most common cranial nerve affected in both pediatric and adult patients with vertical and/or torsional diplopia. The condition has multiple known etiologies, including schwannoma, which is rarely reported in the literature. Schwannoma should be considered when the most common etiologies have been ruled out. PURPOSE: This report documents a rare case of cranial nerve IV palsy secondary to a trochlear schwannoma. Treatment and management considerations will be discussed. CASE REPORT: A 57-year-old man presented to the clinic for evaluation of his recent-onset vertical diplopia. He was diagnosed with left cranial nerve IV palsy. MRI of the brain and orbits revealed the presence of a schwannoma along the course of his left fourth cranial nerve. It did not compress any other cranial nerves or the brainstem. The patient was referred to the neuro-ophthalmology clinic for further evaluation. He was managed conservatively with prismatic spectacle correction to relieve his diplopia. Repeat MRI of the brain and orbits was recommended every 6 months. CONCLUSIONS: Although rare, schwannoma of the fourth cranial nerve should be considered in cases of cranial nerve IV palsies without an obvious etiology. Neuroimaging of the brain and orbits is warranted in cases where more common etiologies have been ruled out or when other cranial nerves and/or the brainstem are involved.

The Impact of Policy Reform on Utilization of Popular Reconstructive Procedures.

OBJECTIVES: Medicaid beneficiaries systematically face challenges in accessing healthcare, especially with regard to specialty services like reconstructive surgery. This study evaluated the impact of 2 healthcare reform policies, Medicaid expansion and global hospital budgeting, on utilization of reconstructive surgery by Medicaid patients. METHODS: Utilization of reconstructive surgery by Medicaid patients in New Jersey (Medicaid expansion/no global budget), Maryland (Medicaid expansion/with global budgets), and Florida (no Medicaid expansion/no global budget) between 2012 and 2016 was compared using quasi-experimental, interrupted time-series modeling. Subgroup analyses by procedure type and urgency were also undertaken. RESULTS: During the study period, the likelihood of Medicaid patients using reconstructive surgery significantly increased in expansion states (Maryland: 0.3% [95% confidence interval = 0.17% to 0.42%] increase per quarter, P < 0.001; New Jersey: 0.4% [0.31% to 0.52%] increase per quarter, P = 0.004) when compared with Florida (nonexpansion state). Global budgeting did not significantly impact overall utilization of reconstructive procedures by Medicaid beneficiaries. Upon subgroup analyses, there was a greater increase in utilization of elective procedures than emergent procedures by Medicaid beneficiaries after Medicaid expansion (elective: 0.9% [0.8% to 1.3%] increase per quarter, P = 0.04; emergent/urgent: 0.2% [0.1% to 0.4%] increase per quarter, P = 0.02). In addition, Medicaid expansion had the greatest absolute effect on breast reconstruction (1.0% [95% confidence interval = 0.7% to 1.3%] increase per quarter) compared with other procedure types. CONCLUSIONS: Medicaid expansion increased access to reconstructive surgery for Medicaid beneficiaries, especially for elective procedures. Encouragingly, although cost-constrictive, global hospital budgeting did not limit longitudinal utilization of reconstructive surgery by Medicaid patients, who are traditionally at higher risk for complications/readmissions.

Pediatric Tissue Expansion: Predictors of Premature Expander Removal in a Single Surgeon's Experience with 472 Expanders.

BACKGROUND: Tissue expansion is used for soft-tissue reconstruction in pediatric patients. The expansion process can be complicated by infection and extrusion, leading to premature expander removal. The aim of this study was to identify risk factors associated with premature expander removal caused by infection or extrusion in pediatric patients. METHODS: A retrospective study of pediatric patients who underwent tissue expansion performed by the senior author (R.J.R.) over a 12-year period was performed. Predictor variables included age, sex, race, indication, anatomical location, number of expanders, serial expansion, and expander size. Bivariate and multivariate analyses were performed to identify risk factors for premature expander removal. RESULTS: A total of 139 patients with 472 expanders were included in this study. Complications occurred with 78 expanders (16.5 percent). Premature expander removal caused by infection or exposure occurred with 51 expanders (10.8 percent). In terms of location, the highest rates of premature removal occurred in the lower extremity (20.0 percent) and scalp (16.3 percent). Multivariate analysis identified younger age (0 to 6 years compared with 13 to 17 years; OR, 3.98; 95 percent CI, 1.13 to 14.08; p = 0.03), greater number of expanders (OR, 1.45; 95 percent CI, 1.03 to 2.03; p = 0.03), and lower extremity location (OR, 4.27; 95 percent CI, 1.45 to 12.53; p = 0.008) were associated with an increased odds of premature expander removal. CONCLUSIONS: Expander removal occurred in approximately 10 percent of tissue expanders. Odds of premature removal is increased with younger age, greater number of expanders, and lower extremity location. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Poly(ε-Caprolactone) Nanofiber Wrap Improves Nerve Regeneration and Functional Outcomes after Delayed Nerve Repair.

BACKGROUND: The purpose of this study was to assess the efficacy of biodegradable, electrospun poly(ε-caprolactone) nanofiber nerve conduits in improving nerve regeneration. METHODS: The authors used a rat forelimb chronic denervation model to assess the effects of poly(ε-caprolactone) conduits on improving nerve regeneration and upper extremity function. Three groups of rats were examined: (1) negative-control animals (n = 5), which underwent 8 weeks of median nerve chronic denervation injury followed by repair with no conduit; (2) experimental animals (n = 5), which underwent 8 weeks of median nerve chronic denervation followed by repair and poly(ε-caprolactone) nerve conduit wrapping of the nerve coaptation site; and (3) positive-control animals (n = 5), which were naive controls. All animals underwent compound muscle action potential and functional testing. At 14 weeks after repair, the median nerve and flexor muscles were harvested for histologic analysis. RESULTS: Histomorphometric analysis of regenerating median nerves demonstrated augmented axonal regeneration in experimental versus negative control animals (total axon count, 1769 ± 672 versus 1072 ± 123.80; p = 0.0468). With regard to functional recovery, experimental and negative-control animals (1.67 ± 0.04 versus 0.97 ± 0.39; p = 0.036) had regained 34.9 percent and 25.4 percent, respectively, of baseline hand grip strength at 14 weeks after repair. Lastly, less collagen deposition at the nerve coaptation site of experimental animals was found when compared to control animals (p < 0.05). CONCLUSION: Biodegradable, poly(ε-caprolactone) nanofiber nerve conduits can improve nerve regeneration and subsequent physiologic extremity function in the setting of delayed nerve repair by decreasing the scar burden at nerve coaptation sites.

Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury.

This study investigates the efficacy of systemic growth hormone (GH) therapy in ameliorating the deleterious effects of chronic denervation (CD) injury on nerve regeneration and resulting motor function. Using a forelimb CD model, 4 groups of Lewis rats were examined (n = 8 per group): Group-1 (negative control) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer; Group-2 (experimental) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer and highly purified lyophilized pituitary porcine GH treatment (0.6 mg/day); Group-3 (positive control) immediate ulnar-to-median nerve transfer without CD; Group-4 (baseline) naïve controls. All animals underwent weekly grip strength testing and were sacrificed 14 weeks following nerve transfer for histomorphometric analysis of median nerve regeneration, flexor digitorum superficialis atrophy, and neuromuscular junction reinnervation. In comparison to untreated controls, GH-treated animals demonstrated enhanced median nerve regeneration as measured by axon density (p < 0.005), axon diameter (p < 0.0001), and myelin thickness (p < 0.0001); improved muscle re-innervation (27.9% vs 38.0% NMJs re-innervated; p < 0.02); reduced muscle atrophy (1146 ± 93.19 µm2 vs 865.2 ± 48.33 µm2; p < 0.02); and greater recovery of motor function (grip strength: p < 0.001). These findings support the hypothesis that GH-therapy enhances axonal regeneration and maintains chronically-denervated muscle to thereby promote motor re-innervation and functional recovery.

Mary Edwards Walker (1832-1919): Approach to limb salvage therapy.

Mary Edwards Walker (1832-1919) was the first female surgeon in the United States. Her upbringing and unique medical training led her to practice medicine in a way that was revolutionary for the time. During the Civil War, her approach to wound care rivaled the current standard of care. During an era that predated antiseptic surgical technique, she prioritized cleanliness and hygiene. She opposed amputation for its surgical risks and decreased postoperative quality of life. She believed that many wounds, when appropriately attended to, would heal without amputation. She advocated for patients who she believed did not require amputations and counseled them on their rights to refuse surgical care.

Selective Thumb Carpometacarpal Joint Denervation for Painful Arthritis: Clinical Outcomes and Cadaveric Study.

PURPOSE: To determine the innervation pattern to the thumb carpometacarpal (CMC) joint and assess the safety and efficacy of selective joint denervation for the treatment of pain and impairment associated with thumb CMC arthritis. METHODS: Cadaveric dissections were performed in 10 fresh upper extremities to better define the innervation patterns to the CMC joint and guide the surgical approach for CMC joint denervation. Histologic confirmation of candidate nerves was performed with hematoxylin and eosin staining. Results from a series of 12 patients with symptomatic thumb CMC arthritis who underwent selective denervation were retrospectively evaluated to determine the safety and efficacy of this treatment approach. Differences in preoperative and postoperative measurements of grip and key-pinch strength as well as subjective reporting of symptoms were compared. RESULTS: Nerve branches to the thumb CMC joint were found to arise from the lateral antebrachial cutaneous nerve (10 of 10 specimens), the palmar cutaneous branch of the median nerve (7 of 10 specimens), and the radial sensory nerve (4 of 10 specimens). With an average follow-up time of 15 months, 11 of 12 patients (92%) reported complete or near-complete relief of pain. Average improvements in grip and lateral key-pinch strength were 4.1 ± 3.0 kg (18% ± 12% from baseline) and 1.7 ± 0.5 kg (37% ± 11% from baseline), respectively. One patient experienced the onset of new pain consistent with a neuroma that resolved with steroid injection. All patients were released to light activity at 1 week after surgery, and all activity restrictions were lifted by 6 weeks after surgery. CONCLUSIONS: Selective denervation of the CMC joint is an effective approach to treat pain and alleviate impairment associated with CMC arthritis. The procedure is well tolerated, with faster recovery as compared with trapeziectomy. Branches arising from the lateral antebrachial cutaneous nerve, palmar cutaneous branch of the median nerve, and radial sensory nerve can be identified and resected with a single-incision Wagner approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Muscle-Derived Stem Cell-Enriched Scaffolds Are Capable of Enhanced Healing of a Murine Volumetric Muscle Loss Defect.

BACKGROUND: Volumetric muscle loss secondary to traumatic or surgical causes can lead to functional and aesthetic impairments. The authors hypothesize that an implantable muscle-derived stem cell-enriched collagen scaffold could significantly augment muscle regeneration in a murine model of volumetric muscle loss. METHODS: Murine muscle-derived stem cells were isolated using a modified preplating technique and seeded onto type 1 collagen scaffolds to create the muscle-derived stem cell-enriched collagen scaffolds. Murine rectus femoris defects of 5 mm were created and randomized to one of three conditions (n = 6 per group): untreated controls, collagen scaffold only, and muscle-derived stem cell-enriched collagen scaffolds. In vivo muscle healing was quantified using micro-computed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks. RESULTS: In vivo experiments demonstrated significantly greater quadriceps cross-sectional area in the muscle-derived stem cell-enriched collagen scaffold group compared with controls on micro-computed tomography (0.74 ± 0.21 versus 0.55 ± 0.06 versus 0.49 ± 0.04 ratio of experimental to naive quadriceps cross-sectional area; p < 0.05). Muscle explants of the muscle-derived stem cell-enriched collagen scaffold group demonstrated significantly higher cellular density compared with controls (1185 ± 360 versus 359 ± 62 versus 197 ± 68 nuclei/high-power field; p < 0.01). Immunofluorescence for laminin and myosin heavy chain confirmed formation of organized muscle fibers within the defect of the muscle-derived stem cell-enriched collagen scaffold group only. However, appreciable confocal colocalization of myosin heavy chain with green fluorescent protein expression was low. CONCLUSIONS: The results of this study indicate that muscle-derived stem cell-enriched scaffolds significantly improved skeletal muscle regeneration in a murine muscle defect model. Based on the low fluorescent colocalization, host progenitor cells appear to contribute significantly to intradefect myogenesis, suggesting that deployment of a viable muscle-derived stem cell-enriched scaffold stimulates a regenerative mitogen response in native tissues.

Desensitization and Prevention of Antibody-Mediated Rejection in Vascularized Composite Allotransplantation by Syngeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection. Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent antibody-mediated rejection in VCA. METHODS: Skin transplants from Dark Agouti to Lewis rats were performed for sensitization. Orthotopic hind limb transplants from Dark Agouti donors were performed to sensitized and nonsensitized recipients, and the animals were treated with either daily tacrolimus or no immunosuppression. A desensitization protocol consisting of total body irradiation, fludarabine, and syngeneic HSCT was applied to sensitized animals. Graft rejection was monitored by clinical assessment and histological analysis. Serum levels of donor-specific antibodies (DSA IgG) were measured using flow cytometry. RESULTS: Sensitized recipients exhibited accelerated rejection by 5.5 ± 1.2 days without immunosuppression and 10.2 ± 3.6 days with daily tacrolimus compared with 8.7 ± 1.2 days and longer than 30 days in nonsensitized recipients, respectively. Serum levels of DSA IgG were markedly elevated (37.3 ± 3.34-fold from baseline) in sensitized recipients after VCA and correlated with histologic evidence of rejection and C4d deposition. Desensitization significantly reduced DSA compared with sensitized controls (2.6 ± 0.5-fold vs 6.0 ± 1.2-fold, P < 0.01) and along with daily tacrolimus led to improved VCA survival longer than 30 days without evidence of C4d deposition (n = 6). CONCLUSIONS: In summary, sensitization leads to accelerated rejection of VCA, and syngeneic HSCT combined with conventional immunosuppression effectively reduces DSA and improves allograft survival in sensitized rats.

Trends, Frequency, and Nature of Surgeon-Reported Conflicts of Interest in Plastic Surgery.

BACKGROUND: The purpose of this study was to identify types and trends in industry sponsorship of plastic surgery research since the establishment of conflict-of-interest reporting policies in plastic surgery. METHODS: The authors analyzed the frequency and types of self-reported conflicts of interest in the plastic surgery literature since the adoption of reporting policies in 2007. All original articles that met the authors' inclusion criteria and were published in the following three journals from 2008 to 2013 were included: Annals of Plastic Surgery, Plastic and Reconstructive Surgery, and Journal of Plastic, Reconstructive & Aesthetic Surgery. A multivariate regression analysis was performed to determine what study-specific variables were associated with conflict-of-interest disclosures. RESULTS: A total of 3722 articles were analyzed. The incidence of conflicts of interest increased from 14 percent in 2008 to 24 percent in 2009. However, thereafter, the incidence of conflicts of interest decreased steadily from 21 percent in 2010 to 9 percent in 2013. Furthermore, the authors' analysis revealed that from 2008 to 2013, industry decreased direct research support but steadily increased the rate of consultantships (p < 0.001). A multivariate regression analysis revealed that, after adjusting for potential confounders, self-reported conflicts of interest have decreased since 2008 (p = 0.03) and the prevalence of conflicts of interest differs by plastic surgery subspecialty (p < 0.0001), country of origin (p < 0.0001), and journal of publication (p = 0.05). CONCLUSIONS: If self-reporting of conflicts of interest is assumed to be accurate, the number of surgeon-reported conflicts of interest in plastic surgery declined overall. Although the absolute number of consultantships did not change, the rate of consultantships rather than direct research support increased over this period.

Vascular Endothelial Growth Factor Induction of Muscle-Derived Stem Cells Enhances Vascular Phenotype While Preserving Myogenic Potential.

BACKGROUND: Previous work by our group and other laboratories have revealed that muscle-derived stem cells (MDSCs) may contain both myogenic and endothelial progenitors, making MDSCs a promising option for skeletal muscle regeneration. The purpose of this study was to investigate the impact of vascular endothelial growth factor (VEGF) induction on the vascular and myogenic potential of MDSCs. METHODS: Muscle-derived stem cells were isolated from 4- to 8-week-old C57BL/6J mice using a preplate technique and recombinant human VEGFa was used as the induction agent. Cellular proliferation and migration were assessed using serial imaging and wound healing assays, respectively. Myosin heavy chain staining was performed to assess MDSC myotube formation. Vascular potential of MDSCs was measured by expression of CD31 and in vitro capillary tube formation. RESULTS: Vascular endothelial growth factor stimulation led to a dose-dependent increase in MDSC proliferation (P < 0.05) and migration kinetics (P < 0.01). Control MDSCs had low levels of baseline expression of CD31, which was significantly upregulated by VEGF stimulation. Similarly, MDSCs demonstrated a basal capability for capillary tube formation, which was significantly increased after VEGF induction as evidenced by increased branches (5.91 ± 0.58 vs 9.23 ± 0.67, P < 0.01) and total tube length (11.73 ± 0.97 vs 18.62 ± 1.57 mm, P < 0.01). Additionally, the myogenic potential of MDSCs as measured by fusion index remained unchanged with increasing concentration of VEGF up to 250 ng/mL (P = 0.77). CONCLUSIONS: Vascular endothelial growth factor induction enhances MDSC proliferation, migration, and endothelial phenotypes without negatively impacting myogenic potential. These results suggest that VEGF stimulation may improve vascularization of MDSC-based strategies for skeletal muscle regeneration.

Immune-Modulating Therapy for Rheumatologic Disease: Implications for Patients with Diabetes.

Immune modulators used to treat rheumatologic disease have diverse endocrine effects in patients with diabetes. Providers should be aware of these effects given that diabetes and rheumatologic disease overlap in prevalence and cardiovascular morbidity. In patients with type 1 diabetes, clinical trials have demonstrated that immune modulators used early in the disease can improve pancreatic function, though their efficacy in adults with longstanding autoimmune diabetes is unknown. In patients with type 2 diabetes, hydroxychloroquine is an effective antihyperglycemic and may be preferred for rheumatologic use in patients with difficult glycemic control. In patients without diabetes, hydroxychloroquine and tumor necrosis factor (TNF) inhibitors have been found to decrease diabetes incidence in observational studies. Additionally, dapsone and sulfasalazine alter erythrocyte survival resulting in inaccurate HbA1c values. These multifaceted effects of immune modulators create a need for coordinated care between providers treating patients with diabetes to individualize medication selection and prevent hypoglycemic events. More research is needed to determine the long-term outcomes of immune modulators in patients with diabetes.

Histone modifications influence mediator interactions with chromatin.

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator-histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization.