Establishment and characterization of equine mammary organoids using a method translatable to other non-traditional model species.

Mammary organoid (MaO) models are only available for a few traditional model organisms, limiting our ability to investigate mammary gland development and cancer across mammals. This study established equine mammary organoids (EqMaOs) from cryopreserved mammary tissue, in which mammary tissue fragments were isolated and embedded into a 3D matrix to produce EqMaOs. We evaluated viability, proliferation and budding capacity of EqMaOs at different time points during culture, showing that although the number of proliferative cells decreased over time, viability was maintained and budding increased. We further characterized EqMaOs based on expression of stem cell, myoepithelial and luminal markers, and found that EqMaOs expressed these markers throughout culture and that a bilayered structure as seen in vivo was recapitulated. We used the milk-stimulating hormone prolactin to induce milk production, which was verified by the upregulation of milk proteins, most notably ß-casein. Additionally, we showed that our method is also applicable to additional non-traditional mammalian species, particularly domesticated animals such as cats, pigs and rabbits. Collectively, MaO models across species will be a useful tool for comparative developmental and cancer studies.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease.

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study.

OBJECTIVES: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study. METHODS: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0. RESULTS: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48. CONCLUSIONS: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48. TRIAL REGISTRATION NUMBER: NCT01500551.

Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score.

BACKGROUND: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)-positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. METHODS: Using the SEER Oncotype database, we estimated propensity score-weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I-II, axillary node-negative, invasive breast cancer according to race/ethnicity. RESULTS: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28-0.81), Hispanic (HR, 0.48; 95% CI, 0.25-0.94), and NHW (HR, 0.80; 95% CI, 0.65-0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28-1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20-0.67]; NHW: HR, 0.56 [95% CI, 0.44-0.74]; Pinteraction for chemotherapy * race <.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. CONCLUSIONS: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis.

BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown. METHODS: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease. RESULTS: A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups. CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).

Building Blocks of Wellness: Where Do We Start When Our Tasks Have No End?

Surgeon wellness, and the means by which it may be realized, has recently come to the forefront as awareness of burnout among orthopaedic surgeons has increased. Individual surgeons face unique challenges toward finding their own path to thrive. It is important to incorporate varying perspectives regarding potential solutions to surgeons' stresses in both work and extracurricular life. Specifically, the goal is to initiate a discussion regarding wellness by providing insight into the challenges facing surgical residents, supplemented with the perspectives of women and minorities within the field. Peer coaching plays an essential role in optimizing mental health.

Policies, Practices, and Attitudes Related to Parental Leave for Practicing Pediatric Orthopaedic Surgeons.

BACKGROUND: Parental leave impacts family engagement, bonding, stress, and happiness. Because parental leave benefits are important to all surgeons regardless of sex, understanding parental leave practices in pediatric orthopaedic surgery is critical to promote equity within the profession and supporting balance in work and family life. The aim of this study was to survey pediatric orthopaedic surgeons about their knowledge of parental leave policies, attitudes towards parental leave, and their individual experiences taking leave. METHODS: A 34-question anonymous survey was distributed to the Pediatric Orthopaedic Society of North America membership. Eligible respondents were attending pediatric orthopaedic surgeons practicing in the United States or Canada. The survey gathered information about employer parental leave policies, perceptions about and experiences with parental leave while practicing as a surgeon, and demographic information about respondents. RESULTS: A total of 77 responses were completed and used for analysis. Most respondents were men (59.7%), <50 years old (67.5%), married (90.9%), and in urban communities (75.3%). A large majority were practicing in the United States (97.4%). Most respondents were unfamiliar with employer parental leave policies (maternity: 53.3%; paternity: 67.5%; and adoption: 85.7%). Those familiar with policies reported that employers offered 7 to 12 weeks for maternity leave (45.7%) and <1 week for paternity leave (50%) and adoption leave (45.5%). Most respondents believed 7 to 12 weeks should be offered for maternity leave (66.2%), 1 to 6 weeks for paternity leave (54.6%), and 7 to 12 weeks for adoption leave (46.8%). Many respondents reported taking 1 to 6 weeks of parental leave as a surgeon (53.3%) and that their colleagues were supportive of their parental leave (40.3%). CONCLUSIONS: Most pediatric orthopaedic surgeons were unfamiliar with parental leave benefits provided by employers. Respondents who were familiar with these policies believed that more parental leave should be provided, especially for men who may feel social pressure to take less time for leave. Although respondents reported that their work environments were supportive, this study identified opportunities for improvement to support surgeons who wish to balance parental experiences with work responsibilities. LEVEL OF EVIDENCE: Level V.

Detection of High-Risk Sessile Serrated Lesions: Multitarget Stool DNA Versus CT Colonography.

BACKGROUND. The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Sessile serrated lesions (SSLs) that are large (≥ 10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of noninvasive screening tests for detection of high-risk SSLs is unclear. OBJECTIVE. The aim of this study was to compare noninvasive screening detection of high-risk SSLs between the multitarget stool DNA (mt-sDNA) test and CT colonography (CTC). METHODS. This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age, 60.0 years) who underwent CRC screening at a single center by mt-sDNA from 2014 to 2019 (n = 3987) or by CTC from 2009 to 2019 (n = 3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. RESULTS. The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p = .23) and 6.5% (260/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA versus 14.4% (66/457; p < .001) and 25.9% (63/243; p < .001) for CTC at the 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; p < .001) and 1.6% (63/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. CONCLUSION. CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. CLINICAL IMPACT. The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.

Chemoprevention of Colorectal Cancer.

Although colorectal cancer (CRC) screening has reduced the incidence of and mortality from CRC, chemoprevention strategies have the potential to further reduce CRC incidence and mortality. Chemoprevention agents might be used for average-risk as well as high-risk groups, and to prevent CRC recurrence after therapy. CRC chemoprevention agents that have been studied include aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, statins, agents that target metabolic pathways, and vitamins and minerals. We review the prospect of chemoprevention of CRC, results from preclinical and human studies, challenges, and future directions.

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. RESULTS: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. CONCLUSION: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279.

Using Statewide Electronic Health Record and Influenza Vaccination Data to Plan and Prioritize COVID-19 Vaccine Outreach and Communications in Wisconsin Communities.

The University of Wisconsin Neighborhood Health Partnerships Program used electronic health record and influenza vaccination data to estimate COVID-19 relative mortality risk and potential barriers to vaccination in Wisconsin ZIP Code Tabulation Areas. Data visualization revealed four groupings to use in planning and prioritizing vaccine outreach and communication based on ZIP Code Tabulation Area characteristics. The program provided data, visualization, and guidance to health systems, health departments, nonprofits, and others to support planning targeted outreach approaches to increase COVID-19 vaccination uptake. (Am J Public Health. 2021;111(12):2111-2114. https://doi.org/10.2105/AJPH.2021.306524).

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening.

BackgroundMultitarget stool DNA (mt-sDNA) screening has increased rapidly since simultaneous approval by the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services in 2014, whereas CT colonography screening remains underused and is not covered by Centers for Medicare and Medicaid Services.PurposeTo report postapproval clinical experience with mt-sDNA screening for colorectal cancer (CRC) and compare results with CT colonography screening at the same center.Materials and MethodsIn this retrospective cohort study, asymptomatic adults underwent clinical mt-sDNA screening during a 5-year interval (2014-2019). Electronic medical records were searched to verify test results and document subsequent optical colonoscopy and histopathologic findings. A similar analysis was performed for CT colonography screening during a 15-year interval (2004-2019), with consideration of thresholds for positivity of both 6-mm and 10-mm polyp sizes. χ2 or two-sample t tests were used for group comparisons.ResultsA total of 3987 asymptomatic adult patients (mean age, 64 years ± 9 [standard deviation]; 2567 women) underwent mt-sDNA screening and 9656 patients (mean age, 57 years ± 8; 5200 women) underwent CT colonography. Test-positive rates for mt-sDNA and for 6-mm- and 10-mm-threshold CT colonography were 15.2%, 16.4%, and 6.7%, respectively. Optical colonoscopy follow-up rates for positive results of mt-sDNA and 6-mm- and 10-mm-threshold CT colonography were 13.1%, 12.3%, and 5.9%, respectively. Positive predictive values (PPVs) for any neoplasm 6 mm or greater, advanced neoplasia, and CRC for mt-sDNA were 54.2%, 22.7%, and 1.9% respectively; for 6-mm-threshold CT colonography, PPVs were 76.8%, 44.3%, and 2.7%; for 10-mm-threshold CT colonography, PPVs were 84.5%, 75.2%, and 5.2%, respectively (P < .001 for mt-sDNA vs CT colonography for all except 6-mm CRC at CT colonography). For mt-sDNA versus 6-mm-threshold CT colonography, overall detection rates for advanced neoplasia were 2.7% and 5.0%, respectively (P < .001); corresponding detection rates for CRC were 0.23% and 0.31%, respectively (P = .43).ConclusionThe detection rates of advanced neoplasia at CT colonography screening were greater than those of multitarget stool DNA. Detection rates were similar for colorectal cancer.© RSNA, 2020See also the editorial by Yee in this issue.

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age to initiate screening in average risk individuals and follow-up for low-risk adenomas.

Does the Proportion of Women in Orthopaedic Leadership Roles Reflect the Gender Composition of Specialty Societies?

BACKGROUND: Increasing the number of women in surgical subspecialties has been challenging, especially in orthopaedics, in which the percentage of women has remained relatively the same for the past several decades. Certain subspecialties, such as pediatric orthopaedics, have a greater proportion of women than other orthopaedic subspecialties do. Women in leadership roles in a specialty society (for example, on the board of directors) may serve as role models and help attract women to our specialty, leading to increased diversity. As the proportion of women in a specialty society increases, the leadership (board of directors) of the society might reflect the gender composition of that society's membership. It is not known whether gender diversity in orthopaedic societies is reflected in their leadership. QUESTION/PURPOSES: (1) Does the percentage of women members in a specialty society correlate with the percentage of women on its board of directors? (2) Does having a junior position on an orthopaedics subspecialty society's board of directors correlate with an increased percentage of women on its board of directors? METHODS: We queried the executive directors of each of the 23 societies of the Board of Specialty Societies of the American Academy of Orthopaedic Surgeons to obtain the number and percentage of women members in each society, the number of women on each society's board of directors, the criteria for becoming a board member, and the presence or absence of junior board members. All 23 societies responded. We supplemented the data by reviewing these societies' bylaws. Society bylaws were studied to determine if the presence of a junior board member affected the percentage of women on its board of directors. We correlated the percentage of women in each society with the percentage of women on that society's board of directors and compared this across the studied societies. RESULTS: We found a strong correlation between the percentage of women in a society and the percentage of women on the society's board of directors (r = .2333; p = .0495). The subspecialty society with the highest percentage of women (26%), the Pediatric Orthopaedic Society of North America, did not have the highest percentage of women on its board of directors (three of 20 members were women, 15%). The subspecialty society with the highest percentage of women on its board of directors, the Orthopaedic Research Society (seven of 16 members, 44%), did not have the highest percentage of women (25%). There was no correlation between presence of a junior board member and increased percentage of women in an orthopaedic society, nor was there a correlation between the presence of a junior board member and percentage of women on the board of directors in a society. CONCLUSIONS: There is a correlation between the number of women members in an orthopaedic specialty society and the number of women on its board of directors. The correlation is not explained by the presence of a junior member position, which may be inspiring to younger women. Although a correlation exists, we could not predictably match societies with the highest percentage of women members to those with the highest percentage of women on their boards of directors, and vice versa. This study reveals the current percentage of women in orthopaedic specialty societies and the percentage of women in leadership positions. This is the first step towards diversity of gender in orthopaedics. LEVEL OF EVIDENCE: Level III, prognostic study.

Wellness and Drivers of Burnout.

INTRODUCTION: Promoting physician wellness in the current environment of increasing burnout presents a great challenge to the Pediatric Orthopaedic Society and its members. Pediatric Orthopaedic Society of North America (POSNA) has been a leader in recognizing this problem and organizing to combat it. The increasing rates of job dissatisfaction, burnout, depression, and suicide demand comprehensive and focused action to identify and address the drivers of burnout. Continuing to ignore this problem endangers our organization, our members, our families, and our patients. METHODS: A review of relevant literature and the work of the POSNA wellness committee was completed. RESULTS: Addressing the epidemic of burnout requires a sustained effort to address intrinsic factors such as health, performance, and resilience as well as external factors that affect practice efficiency and environment. DISCUSSION AND CONCLUSIONS: The goal of this effort is restoration of joy to the practitioners in medicine and more compassionate care for the patients who seek it.

Pediatric Orthopaedists Are Not Immune: Characterizing Self-reported Burnout Rates Among POSNA Members.

BACKGROUND: There are no published data characterizing burnout rates for pediatric orthopaedic surgeons. The primary purpose of this study was to identify the rates of self-reported personal and team burnout among members of the Pediatric Orthopaedic Society of North America (POSNA). A secondary aim was to determine whether specific demographic variables were more likely to be associated with self-reported burnout. METHODS: During its 2018 annual meeting, the POSNA Wellness Taskforce launched a web-based survey in which members were asked to respond to 2 previously validated questions related to personal and team burnout. The survey was distributed by a closed POSNA membership e-mail list and responses were analyzed anonymously. Descriptive statistics were calculated. Pearson χ testing was used to analyze differences in burnout rates as a function of age and sex. RESULTS: A total of 615 POSNA members completed the survey, a 47% response rate. Overall, 38% reported personal burnout and 46% reported team burnout. Women were more likely to report both personal (P<0.001) and team burnouts (P<0.005). Members aged 40 to 59 years were more likely to report personal burnout, irrespective of sex (P<0.001). Members aged 50 to 59 years were more likely than those in other age groups to report team burnout (P<0.001). There was no significant association found between the presence of burnout and either race, ethnicity, LGBTQ status, or educational background. CONCLUSIONS: As a group, pediatric orthopaedists report moderately high rates of both personal and team member burnout. Individual-specific factors such as age and sex may play an important role in determining one's risk for experiencing burnout. Recognizing that burnout affects a significant minority of POSNA members is a crucial first step. LEVEL OF EVIDENCE: Level III.

Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.

Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

Clear liquid diet before bowel preparation predicts successful chromoendoscopy in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Chromoendoscopy (CE) has been shown to generate both a superior diagnostic yield and dysplasia detection rate than conventional white-light endoscopy and requires a high-quality bowel preparation. The aim of this study was to identify predictors of the ability to perform CE in patients with inflammatory bowel disease (IBD). METHODS: We performed an observational study of patients with IBD undergoing colorectal cancer surveillance examinations with CE. Same-day colonoscopy surveys were used to collect patient and procedural variables. Multivariate logistic regression was used to establish odds ratios of successful completion of CE. RESULTS: Eighty-eight patients with IBD were enrolled. We found that patients who did not follow a clear liquid diet before colonoscopy had much lower odds of being able to undergo CE (odds ratio, 0.106; 95% confidence interval, 0.013-0.845; P < .034). Further, we found that previously identified risk factors (older age, history of diabetes mellitus, the timing and split dosing of preparation solution, and procedure time (AM or PM), chronic narcotic use, and history of constipation) for inadequate bowel preparation were not associated with the ability to perform CE. CONCLUSIONS: Following a clear liquid diet the entire day before the procedure was highly predictive of the ability to perform CE. However, established risk factors for inadequate bowel preparation did not inhibit the ability to perform CE in our population. Endoscopists performing CE should consider recommending that patients follow a clear liquid diet the entire day before their examination.