Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia.

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gαs activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors. We performed RNAseq of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, and combined their transcriptomic profiles to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. In addition, a comprehensive profile of their secreted cytokines and other factors was performed to identify modulation of several key factors we hypothesized to be involved in FD pathogenesis. We also screened circulating cytokines in a collection of plasma samples from patients with FD, finding positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers. Overall, these data support a pro-inflammatory, pro-osteoclastic behavior of BMSCs bearing hyperactive Gαs variants, and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

Doctors of Osteopathic Medicine as Plastic Surgery Residents: Demographics, Credentials, and Pathways to Residency.

OBJECTIVE: Doctors of Osteopathic Medicine (DOs) are sparsely represented within plastic and reconstructive surgery (PRS) and recent changes including the elimination of step 1 scoring have further disadvantaged DO applicants. The demographics, degrees, and scholarly output of DO PRS trainees were compared to that of Doctors of Medicine (MDs) to identify areas of focus which could be used to increase competitiveness of DO applications. DESIGN: A cross-sectional study was created, including ACGME-accredited PRS program trainees during the 2020 to 2021 academic year. DO and MD trainee demographics and scholarly accomplishments were compared using t-test and chi-squared analysis. SETTING: Web-based publicly available information was collected for subjects. PARTICIPANTS: A total of 1092 PRS MD and DO trainees were identified. DOs made up only 2.7% (n = 30) and MDs made up 97.3% (n = 1062). RESULTS: More DOs trained in independent programs (63.3%) than integrated (36.7%) compared to MDs (88.2% v. 11.8%, p < 0.001) and more DOs trained at lower ranked PRS programs (60.0% of DOs and 18.1% of MDs trained at Q4 programs, p < 0.001). DOs had fewer publications (median, IQR: 1, [0-2]) compared to MDs (3, [1-8]), fewer citations (0, [0-6]) vs. (10, [1-56]) and lower H-index (1, [0-1]) vs. (1, [1-3]). CONCLUSION: DO candidates should consider research years in the field of PRS and optimize clinical experience opportunities to increase the competitiveness of their PRS applications. Special attention should be paid to providing networking and research opportunities to DOs who lack home institutions.

Prevention and Treatment of Burn Scar Contracture: A Practical Review.

Burn contracture affects close to one-third of all burn patients, leading to significant functional impairment and costs. Effective prevention and treatment strategies are necessary to decrease morbidity and unnecessary costs. This scoping review aimed to summarize prevention and treatment strategies used for management of burn scar contractures published in the literature since 2000. A comprehensive PubMed review was performed in October 2022 to identify methods of burn contracture prevention and treatments. Non-English, duplicate, and unavailable articles were excluded. Data were extracted including publication year, techniques, and outcomes. A total of 327 publications met criteria for inclusion. Most articles were published in 2011 (n = 22). Treatment strategies were discussed in 82.9% of studies, prevention in 16.5%, and both in 0.6%. The most common areas discussed included the upper extremity (n = 127) and neck (n = 102). Flaps were the most frequently used method (n = 208), followed by autografts (n = 89). Most preventative therapies were still in early stages of development. Burn contracture management requires a highly individualized approach with many available reconstructive techniques available. Further research is needed to improve prevention techniques and decrease morbidity and cost to patients.

Another Day, Another 82 Cents: A National Survey Assessing Gender-based Wage Differences in Board-certified Plastic Surgeons.

Background: Of 7461 actively practicing United States American Board of Plastic Surgery certified plastic surgeons, only 17% are women. In relation to this small number, gender inequities within the field have been the source of national discussions. Our study assessed the status of the gender-based wage-gap in plastic surgery and sought to identify possible causes. Methods: An anonymous 43-question survey was distributed to 2981 members of the American Society of Plastic Surgeons in 2021. Male and female responses were compared; an analysis also considering board-certification year was performed. Chi-square and Fisher exact tests were used for bivariate analysis. Continuous variables were compared with two-sample t tests and Wilcoxon rank sum tests. Results: Ten percent of contacted American Society of Plastic Surgeons members responded to our survey. Of the 288 respondents, 111 (38.5%) were women, and 177 (61.5%) were men. Men were more likely to have salaries over $400K USD per year (P < 0.0001). Earlier certification year was associated with pay greater than $400K per year (P = 0.0235) but was insignificant once stratified by gender (women: P = 0.2392, men: P = 0.7268). Earlier certification year was associated with production-based and self-determined wages (P = 0.0097), whereas later board-certification year was associated with nonnegotiable salaries (P < 0.0001). Conclusions: Women are significantly less likely to make salaries comparable to those of male plastic surgeons, related to shorter careers on average. An increase in female representation and career duration within the field is needed to improve the current wage-gap.

Current Views on the New United States Medical Licensing Examination Step 1 Pass/Fail Format: A Review of the Literature.

INTRODUCTION: Residency programs have historically used numerical Step 1 scores to screen applicants, making it a career-defining, high-stakes examination. Step 1 scores will be reported as pass/fail starting in January 2022, fundamentally reshaping the residency application review process. This review aimed to identify opinions of physicians and medical students about the new format, identify arguments in support of or against the change, and determine the implications of this change on the residency selection process. METHODS: A comprehensive PubMed review was performed in May 2021 to identify articles that discussed the new Step 1 format. Non-English and duplicate articles were excluded. Data collected from each article included publication year, specialty, subjects, and key findings. RESULTS: A total of 81 articles were included, 26 of which discussed the impact of the new format within surgical fields (32.1%). Remaining articles discussed the implications within the medical community as a whole (n = 33, 40.7%) and nonsurgical fields (n = 22, 27.2%). Studies suggest Program Directors will rely on Step 2 Clinical Knowledge (CK) scores, medical school reputation, applicant familiarity, Dean's letters, recommendation letters, and research in lieu of numerical Step 1 scores. In addition, concerns have been raised that the new format will disadvantage international, osteopathic, and minority applicants while increasing stress surrounding Step 2 CK. CONCLUSIONS: Within the medical community, there are concerns that Step 2 CK will be used to substitute Step 1 and that resident diversity will diminish due to the new Step 1 format. Holistic candidate consideration will be increasingly important.

Optic disc Edema in patients with fibrous dysplasia/McCune-Albright syndrome: Craniomorphometric analysis and peripapillary retinal nerve fiber layer data.

This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1]. Of these, 7 subjects were diagnosed with optic disc edema. OSIRIX imaging analysis software was used to collect intracranial volume and optic canal diameter for 107 patients, via 3D multiplanar reconstruction (MPR) of ≤5 mm axial CT slices. Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the RNFL for 69 patients. The data can be used to assess typical ranges for intracranial volume, optic canal area, and RNFL in the craniofacial FD/MAS population and to assess ranges concerning for optic disc edema. [1] Raborn LN, Pan KS, FitzGibbon EJ, Collins MT, Boyce AM. Optic disc edema in fibrous dysplasia/McCune-Albright syndrome: Prevalence, etiologies, and clinical implications. Bone. 2021 Feb;143:115661. doi: 10.1016/j.bone.2020.115661. Epub 2020 Sep 24. PMID: 32979536.

Overcoming the Impact of COVID-19 on Surgical Mentorship: A Scoping Review of Long-distance Mentorship in Surgery.

BACKGROUND: Mentorship in the surgical field has been increasingly recognized as a crucial component of career success. Distance mentorship models may be utilized to overcome geographic limitations, increase mentorship access, and strengthen mentoring relationships in surgery. OBJECTIVE: This review aimed to identify the scope of literature on distance mentoring in surgery, the range of its application, its effectiveness, and any gaps in the literature that should be addressed in order to enhance mentorship in the surgical field. DESIGN: A comprehensive PubMed review was performed in January 2021 on distance mentorship of students, trainees, and surgeons in the surgical field. Reviews, replies, and non-English articles were excluded. Data was extracted regarding publication year, author's country, specialty, subjects, aim of mentorship model, and efficacy. RESULTS: 134 total studies met inclusion and exclusion criteria. Most studies were published in 2020, written by authors in the United States, from general surgery, and featured an expert surgeon paired with a more junior fully trained surgeon. In all, 93.3% of studies utilized distance mentorship to enhance surgical skill through telementoring and only 4.5% were focused on mentorship to enhance careers through professional development. The remaining studies utilized distance mentorship models to increase surgical research (0.7%) and clinical knowledge (1.5%). CONCLUSION: The results of this review suggest successful implementation of distance mentoring in surgery through telementoring, but a lack of professionally aimed distance mentorship programs. Amidst COVID-19, distance mentorship is particularly important because of decreased face-to-face opportunity. Future studies in the surgical field should investigate distance mentoring as a means of increasing mentorship for professional development.

Optic disc edema in fibrous dysplasia/McCune-Albright syndrome: Prevalence, etiologies, and clinical implications.

BACKGROUND: Fibrous dysplasia (FD) is a rare disorder of expansile fibro-osseous lesions that may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). Optic disc edema is a potentially serious ophthalmologic finding that has been rarely reported in patients with FD/MAS. The purpose of this study was to investigate the prevalence and potential clinical associations of optic disc edema in a large cohort. METHODS: Clinical records were reviewed from subjects in an ongoing FD/MAS natural history study. Computed Tomography scans were evaluated for the presence of structural craniofacial abnormalities associated with optic disc edema, including Chiari I malformation and space-occupying lesions. Craniomorphometric analyses were performed to determine optic canal diameter and intracranial volume. Statistical analyses were performed to compare clinical and radiographic features between subjects with and without optic disc edema. RESULTS: Optic disc edema was diagnosed in 7/187 subjects, for a prevalence of 3.7%. All subjects with optic disc edema were diagnosed before age 18 years and had mild, non-progressive disease. Radiographic structural abnormalities, including Chiari I malformation, aneurysmal bone cysts, and arachnoid cysts, were associated with higher odds of optic disc edema (odds ratio [OR] 24.3; 95% confidence interval [CI], 4.2 to 121.4; p < 0.01) (OR 18.0; 95% CI, 3.4 to 108.2; p < 0.01). Treatment with leuprolide, a gonadotropin releasing hormone analog, was also associated with optic disc edema (OR 26.0; 95% CI 3.3 to 177.5; p < 0.05). There was no significant association of optic disc edema with other MAS endocrinopathies, medications, optic canal diameter, or intracranial volume. CONCLUSION: Optic disc edema is an uncommon but potentially serious complication of craniofacial FD, which may occur more frequently in pediatric patients and those with structural craniofacial abnormalities. The potential association of leuprolide therapy with optic disc edema in this population warrants further study.