A Systematic Review of Epigenetics of Endometriosis.

Objective: To assess the current literature evaluating the epigenetics of endometriosis in humans. Evidence Review: A systematic review was conducted in accordance with the PRISMA guidelines within PubMed, EBSCOhost, Cochrane Library, Embase, Scopus, and Web of Science Core Collection. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing epigenetics in humans published in English up to January 15th, 2023, were included. Two reviewers independently screened studies evaluating the role of epigenetics in endometriosis. The risk of bias was assessed using Cochrane RoB 2.0 tool and the Newcastle-Ottawa scale. Extracted data were analyzed descriptively. Results: We identified 18.639 studies, of which 57 were included, comprising 1.623 patients with endometriosis and 1.243 controls. Among the 57 studies included, 50 (88%) were case-control studies, and 7 (12%) were cross-sectional. Fifty-nine percent of the studies were Asian, 25% were from America, 14% were European, and 2% were from Africa. Acetylation and methylation were the two main key histone modifications that were centered in this review. Accordingly, we classified the studies as those focusing on genome-wide methylation and those on histone acetylation. Several studies identified an association between endometriosis and hypermethylated genes, including the PGR-B, SF-1, and RASSF1A. The genes HOXA10, COX-2, IL-12B, and GATA6 were found to be hypomethylated in endometriotic tissue by several studies. In regards to histone modification, multiple studies reported that the acetylation levels of histones H3 and H4 affect multiple genes associated with endometriosis. In addition, HDAC2 was found to be elevated in endometriosis patients in two studies. Conclusion: Several studies reported a significant difference between specific genes' methylation levels in endometrial biopsies and normal tissue, which suggests that DNA methylation may play an important role in the modulation of the genotype in endometriotic tissue. Acetylation and methylation are the two key histone modifications leading to differential gene expression in endometriotic tissues. The alterations in gene expression reported by the 57 studies can have direct implications on cell cycle growth, cell cycle arrest, and apoptosis and, therefore, might play a key role in the pathogenesis of endometriosis. This review offers insight that histone modifications need further research to evaluate their role as potential biomarkers and treatment targets for endometriosis. Although several key similarities were reported, there were some disagreements among the results, which might be attributable to the heterogeneity between studies. Further research with a more robust standardization is needed to validate the epigenetic changes in endometriosis.

Open Reduction Internal Fixation vs Primary Arthrodesis for Lisfranc Fracture-Dislocations: A Cost Analysis.

Background: Lisfranc fracture-dislocation is an uncommon but serious injury that currently lacks universal consensus on optimal operative treatment. Two common fixation methods are open reduction and internal fixation (ORIF) and primary arthrodesis (PA). The objective of this study is to analyze the cost difference between ORIF and PA of Lisfranc injuries, along with the contribution of medical services to overall costs. Methods: This was a retrospective cost analysis of the MarketScan database from 2010 to 2020. MarketScan is an insurance and commercial claims database that integrates deidentified patient information. It captures person-specific clinical utilization, expenditures, and enrollment across inpatient and outpatient services. Patients undergoing primary ORIF (CPT code 28615) vs PA (28730 and 28740) for Lisfranc fracture-dislocation were identified. The primary independent variable was ORIF vs PA of Lisfranc injury. Total costs due to operative management was the primary objective. The utilization of and costs contributed by medical services was a secondary outcome. Results: From 2010 to 2020, a total of 7268 patients underwent operative management of Lisfranc injuries, with 5689 (78.3%) ORIF and 1579 (21.7%) PA. PA was independently associated with increased net and total payment and coinsurance, clinic visits, and imaging, and patients attended significantly more PT sessions. Conclusion: Using this large database that does not characterize severity or extent of injury, we found that treatment of Lisfranc fracture-dislocation with ORIF was associated with substantially lower initial episode of treatment costs compared with PA. Specific excessive cost drivers for PA were clinic visits, PT sessions, and imaging. Level of Evidence: Level III, retrospective cohort study.

The Mentee Perspective: Evaluating Mentorship of Medical Students in the Field of Orthopaedic Surgery.

INTRODUCTION: Mentorship is an invaluable facet of medical education. The purpose of this study was to analyze medical student perspectives of mentorship they received and the influence this has on their participation in the field of orthopaedic surgery. METHODS: We conducted a cross-sectional study of medical students interested in pursuing orthopaedic surgery through an 18-question survey distributed through social media and e-mail. RESULTS: Two hundred fifteen students completed this survey, with over 50% of students reporting that they have a mentor in orthopaedic surgery while 34% were actively seeking one. Most students found mentors through research opportunities (25%) and cold e-mails (20%). Common hurdles to mentorship were access (38%) and finding common time (30%). Peer mentorship had a higher mean satisfaction score in all domains, except facilitating matching, and there was a significant difference between groups (e.g., peer mentor versus program director; P < 0.001). Sex, race, and degree type were not significantly related to students' access to or their evaluation of mentors (P > 0.05 for all). CONCLUSION: Overall, this study demonstrates that medical students across the nation rely on mentorship to guide them on their path to becoming an orthopaedic surgeon.

Operative vs Nonoperative Management of Achilles Tendon Rupture: A Cost Analysis.

Background: Achilles tendon rupture (ATR) is a common injury with a growing incidence rate. Treatment is either operative or nonoperative. However, evidence is lacking on the cost comparison between these modalities. The objective of this study is to investigate the cost differences between operative and nonoperative treatment of ATR using a large national database. Methods: Patients who received treatment for an ATR were abstracted from the large national commercial insurance claims database, Marketscan Commercial Claims and Encounters Database (n = 100 825) and divided into nonoperative (n = 75 731) and operative (n = 25 094) cohorts. Demographics, location, and health care charges were compared using multivariable regression analysis. Subanalysis of costs for medical services including clinic visits, imaging studies, opioid usage, and physical therapy were conducted. Patients who underwent secondary repair were excluded. Results: Operative treatment was associated with increased net and total payments, coinsurance, copayment, deductible, coordination of benefits (COB) / savings, greater number of clinic visits, radiographs, magnetic resonance imaging (MRI) scans, and physical therapy (PT) sessions, and with higher net costs due to clinic visits, radiographs, MRIs, and PT (P < .001). Operative repair at an ambulatory surgical center was associated with a lower net and total payment, and a significantly higher deductible compared to in-hospital settings (P < .001). Both cohorts received similar numbers of opioid prescriptions during the study period. Yet, operative patients had a significantly shorter duration of opioid use. After controlling for confounders, operative repair was also independently associated with lower net costs due to opioid prescriptions. Conclusion: Compared with nonoperatively managed ATR, surgical repair is associated with greater costs partially because of greater utilization of clinic visits, imaging, and physical therapy sessions. However, surgical costs may be reduced when procedures are performed in ambulatory surgery centers vs hospital facilities. Nonoperative treatment is associated with higher prescription costs secondary to longer duration of opioid use. Level of Evidence: Level III, retrospective cohort study.

AAMC Guidance on Interviewing for the 2022-2023 Residency Application Cycle: Orthopaedic Program Director Perspectives.

In May 2022, the Association of American Medical Colleges (AAMC) published guidelines regarding interviews for the 2022-2023 residency application cycle. These guidelines recommended virtual interviews and discouraged "hybrid" interviewing. We conducted a survey of orthopaedic program directors (PDs) to understand their perspectives on these new guidelines and their plans for the upcoming cycle. Methods: A 19-question multicenter, cross-sectional research survey was emailed to 98 PDs (38.8% response rate) through Qualtrics XM. Contact information was obtained from a public national database. Results: Most orthopaedic residency programs (60.5%) were planning on conducting in-person interviews before any AAMC and hospital guidelines, and most (65.8%) will likely be conducting virtual interviews post-guidelines. PDs voiced mixed opinions about virtual interviews (39.4% in favor vs. 47.4% against). PDs were also split on whether forgoing the AAMC guidance would be irresponsible for residency programs (47.4% believe it would be irresponsible vs. 44.8% believe it would not); however, a plurality are in favor of the AAMC's guidance (42.1%). Furthermore, PDs agreed that virtual interviews have disadvantages including favoring top-tier applicants, students from home institutions, and in-person rotators, making ranking applicants and learning about a program's culture more difficult. Most PDs (84.2%) felt that hybrid interviews would disadvantage applicants who would choose the virtual option. Conclusion: AAMC guidance seems to be influencing how most orthopaedic surgery programs will conduct residency interviews for the 2022-2023 cycle. Most PDs agreed with the AAMC guidelines but voiced concerns regarding several disadvantages for all 3 proposed interview options (virtual, in-person, and hybrid). Our results indicate that the recent AAMC guidelines may have contributed to a shift in opinions among PDs but are not sufficient to create a consensus on the best practices for residency interviews. Our findings should encourage solutions focused on the deeper systemic issues within the orthopaedic application process in the post-coronavirus 2019 pandemic era.

Estimates of infertility in the United States: 1995-2019.

OBJECTIVE: To estimate the changes in infertility from 1995-2019 and determine the association of individual-level characteristics with fertility in the United States. DESIGN: Cross-sectional study. SETTING: Periodic data from 1995, 2002, 2006-2010, 2011-2013, 2013-2015, 2015-2017, and 2017-2019 cycles of the National Survey for Family Growth were used for this analysis. The National Survey for Family Growth comprises samples of the household-level population of women aged 15-44 years in the United States. PATIENT(S): Surveyed married and cohabiting women aged 15-44 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcomes were the rates of infertility across subgroups of married or cohabiting women. For secondary outcomes, we performed bivariable and multivariable logistic regression models using the pooled sample (N = 53,764) to determine the association of individual-level characteristics, including age, parity, pelvic inflammatory disease treatment, education, income, race or ethnicity, and receipt of sexual and reproductive health services, with the odds of 12-month infertility among married or cohabiting women. RESULT(S): The fluctuations in infertility over this period, with a low of 5.8% in 2006-2010 and a high of 8.1% in 2017-2019, were not found to be statistically significant. This trend was present across nearly all subgroups. The multivariable model showed that women who were older and nulliparous, had fewer years of education, had lower income, were non-Hispanic black, or were not receiving sexual and reproductive health services were more likely to be infertile. CONCLUSION(S): This study confirms that parity, age, race, and education level continue to have an association with infertility. Further, the results demonstrate that access to sexual and reproductive health services plays an important role in infertility. In contrast to previous studies, infertility in the United States is no longer on the decline, and Hispanic ethnicity did not have a significant relationship with infertility. Given the rise of sexually transmitted infections and the persistent lack of access to sexual and reproductive health services, particularly among already vulnerable groups, the connection between access to care and infertility is ripe for further investigation.