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PURPOSE GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time ( P < .001) for all three groups. A group by time interaction ( P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.

The primary focus of this study was to understand obesity and depressive symptoms in college women. Using non-obese women as a contrast group, obese and non-obese women were compared on body image and psychological adjustment. Additional analyses further examined the obese women by comparing obese women with high versus low depressive symptoms. A total of 51 obese and 524 non-obese college women completed an online survey. Obese women had significantly lower body image and self-esteem and higher depressive symptoms than non-obese women. Obese women with high depressive symptoms reported more eating problems and poorer body image than obese women with low depressive symptoms. Qualitative coding identified factors linked to low depressive symptoms in obese women including: more positive histories of interpersonal relationships; resisting the internalization of weight bias; and other areas of competence taking the focus off of body image experiences. Implications of these findings for intervention design are considered.

Objective: Cervical cancer is a highly preventable malignancy caused by HPV that begins with the development of precancerous lesions (high risk cervical intraepithelial neoplasia grades 2 or 3 - hrCIN). As cancer is a metabolic disease, individuals with metabolic conditions such as diabetes, high cholesterol (hcho) and high blood pressure (hbp) may be at higher risk of developing hrCIN. Given the higher prevalence among Black women, we sought to determine whether these metabolic conditions increase the risk of hrCIN differentially by race. Methods: We used data from hospital and physician billing claims for any CIN diagnosis occurring at the Virginia Commonwealth University Health System (VCUHS) from 01/01/2014 through 12/04/2021, along with respective clinical and sociodemographic characteristics at the time of diagnosis. We estimated the risk of high-grade dysplasia (CIN2+ versus CIN1) among women with various metabolic diseases, using logistic regression (LR) with a backward selection approach (removing terms with p ≥ 0.2 and adding those with p < 0.1) to identify most relevant confounding factors. Results: There were 2,761 women diagnosed with CIN 1, 2, 3, and unspecified dysplasia of the cervix uteri with respective prevalence of 30%, 45%, 11%, and 14%. The prevalence of hrCIN did not vary by race (48% versus 52% for non-Latina (nL)-whites versus nL-Blacks respectively). Of the variables included in the LR model (age, marital status, religion, preferred language, insurance status, Body Mass Index, HIV, HPV, presence of bacterial vaginosis, hypertension, cholesterol, diabetes, pulmonary conditions, arthritis, heart conditions, pregnancy status, parity, smoking, alcohol, and previous cancer diagnoses), only pregnancy status, diabetes, hypertension, cholesterol, insurance, language, pulmonary conditions, and HPV remained in the final LR model. We identified an interaction between hypertension and cholesterol (p=0.03) where the odds of a hrCIN among women with both, hypertension, and cholesterol, were more than twice compared to women with neither comorbidity (OR=2.2, 95%CI: 1.1, 4.3). Stratified by race, the elevated risk of hrCIN was only significant among nL-Black women (p=0.05, OR=2.9, 95%CI: 1.1, 8.6). Conclusions: Despite no apparent difference in the incidence of hrCIN by race in this dataset, our analysis revealed an excess risk of hrCIN that was only present for Black women with both hypertension and hypercholesterolemia. These comorbidities are both overrepresented in nL-Blacks and are associated with low grade systemic inflammation, which may promote HPV persistence and progression to hrCIN. If replicable, this association deserves further investigation to assess its biological underpinnings and potential as a point of intervention to reduce the risk of CIN progression and cervical cancer. Citation Format: Shreya R. Raman, Stephanie A. Sullivan, Robert A. Winn, Katherine Y. Tossas. "Am I at risk for cervical cancer?": Racial disparity implications of an unexpected relationship between chronic conditions and precancerous lesions [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C098.

Background Lipomatous tumors of the vulva are exceedingly rare, particularly in adolescents. We describe the work-up and management of an adolescent girl who presented with a large, well-vascularized vulvar mass. Case A 14-year-old girl presented with a large vulvar mass of unclear etiology. Magnetic resonance imaging of this mass revealed an ill-defined, well-vascularized mass with fat signal characteristics suggestive of a lipomatous tumor that was concerning for malignancy. We performed complete resection of the mass, and histologic evaluation revealed a vulvar hibernoma. There have been no signs of recurrence 1 year later. Summary and Conclusion Although rare, a hibernoma of the vulvar region may present in adolescence and may be concerning for malignancy on imaging. Complete resection of these tumors is recommended for definitive diagnosis and treatment.

Key Points Question How do children and adolescents with migraine function after participating in a multicenter migraine prevention medication trial? Findings This survey study that followed up 205 participants from the Childhood and Adolescent Migraine Prevention study at 3, 6, 12, 18, 24, and 36 months found that regardless of treatment group (amitriptyline, topiramate, placebo), youth consistently maintained meaningful reductions of headache days and migraine-related disability for 3 years after completion of the trial. Less than 10% of the participants reported ongoing use of prevention medication prescribed as part of typical clinical care, with most participants reporting no medication use at most time points. Meaning These findings suggest that children and adolescents may get better and sustain positive outcomes over time without ongoing pharmacotherapy., This survey study assesses migraine prevalence and disability of participants who completed the Childhood and Adolescent Migraine Prevention trial during 3 years of follow-up., Importance Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained. Objective To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period. Design, Setting, and Participants This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021. Exposures Survey completion. Main Outcomes and Measures Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication. Results A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], −0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points. Conclusions and Relevance These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Background Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. Objectives The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. Methods Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. Results Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß+CD14+CD16+ MFI (−11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (−63, p=0.002) and CD14+CD16+ (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. Conclusions Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production., Highlights • Acute exercise increased monocyte concentrations at 0 h after exercise, with a decrease in CD14+CD16+ monocytes only at 1 h. • Exercise training decreased IL-1β and IL-6 proportions while acute exercise reduced the TLR2 and TLR4 expression. • Anti-inflammatory effect of exercise may be partly explained by reduced pro-inflammatory cytokine production by monocytes.

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (

BACKGROUND Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Objectives: High-grade squamous lesions of the cervix, (Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3), are concerning, common, and costly precancerous findings, particularly for safety net hospitals who provide healthcare regardless of finances or insurance status. Epidemiologic surveillance of these lesions is uncommon but might be useful to guide preventive interventions. We sought to estimate the prevalence of CIN 2/3 and its racial and ethnic distribution, accounting for patient’s clinical and sociodemographic characteristics. Methods: We used data from hospital and physician billing claims for any CIN diagnosis occurring at the Virginia Commonwealth University Health System (VCUHS) from 01/01/2016 through 12/31/2020, along with respective clinical and sociodemographic characteristics at the time of diagnosis. We estimated average adjusted prevalence of CIN 2/3 lesions by race and ethnicity, from average marginal effects, after selecting most relevant patient factors from a logistic regression (LR) using backward selection (removing terms with p ≥ 0.2 and adding those with p < 0.1). Results: There were 1,538 women diagnosed with CIN 1, 2, 3, and unspecified dysplasia of the cervix uteri with respective prevalence of 45%, 14%, 12%, and 30%. CIN2/3 prevalence (26%) varied by race and ethnicity: Asians (39%) > Latinas (32%) > Whites (28%) >Blacks (23%) > Other (20%). Of the variables included in the LR model (age, marital status, religion, preferred language, insurance status, Body Mass Index, HIV, HPV, presence of bacterial vaginosis, hypertension, cholesterol, diabetes, pulmonary conditions, arthritis, heart conditions, pregnancy status, parity, smoking, alcohol, and previous cancer diagnoses), only age, diabetes, pulmonary conditions, smoking, and heart disease remained in the final LR model. The estimated average adjusted prevalence of a CIN 2/3 diagnosis remained highest for Asian women (35%, 95%CI: 17-52%), followed by Latinx (28%, 95%CI: 19-37%), Whites (25%, 95%CI 22-29%), Blacks (23%, 95%CI: 20-27%), and other (18%, 95%CI: 9-26%). Conclusions: The higher CIN 2/3 prevalence estimates among Asian women relative to other races and ethnicities is unexpected, as it does not align with current distribution of cervical cancer diagnoses at VCUHS (only 3% Asian), nor with the patterns of cervical cancer incidence and mortality rates in Virginia and in the United States, where Asian women have the lowest incidence and mortality. However, it potentially suggests a higher rate of regression, a finding supported by at least one surveillance study with similar findings. Citation Format: Shreya R. Raman, Stephanie A. Sullivan, Katherine Y. Tossas. Unexpected pattern in estimated prevalence of precancerous cervical lesions at a safety net hospital in Virginia: A case for epidemiologic surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2208.

Background and aim: Hypertension is a multifactorial condition that is among the leading causes of mortality worldwide. Regulation of blood pressure greatly depends upon the activity of the autonomic nervous system. Alterations in the autonomic nervous system can lead to hypertension. In addition to nervous system control and individual physiologic state, various genes can directly influence autonomic responses. The complexity of blood pressure control is reflected in the 20-30% of individuals resistant to traditional pharmacological treatment, this indicates the need for alternative interventions. This article provides an integrative review and discussion of the key neurophysiologic and genetic factors that contribute to blood pressure regulation, the autonomic nervous system (ANS) and manual therapy literature, and the manual therapy and blood pressure literature. Methods: To assess the effects of chiropractic on the management of hypertension we searched articles published from 1980 to 2019 in PubMed, the Index to Chiropractic Literature and CINAHL, using the keywords: chiropractic, spinal manipulation, hypertension, and blood pressure. Results: We found 38 original studies that analyzed the effect of chiropractic therapy on hypertension. Of these studies, 10 were case reports and the statistical significance of the effects of chiropractic on blood pressure was not evaluated on these articles, so we focused on the remaining 28 articles. Conclusions: The results of the review relative to chiropractic care were promising, but often contradictory, suggesting more research should be done. In consideration of the complexity of ANS blood pressure control, an evaluation of patient presenting physiologic and genetic characteristics is recommended and could provide valuable insight relative to the likelihood of patient blood pressure related responsiveness to care (www.actabiomedica.it)

Background: The Sensory-Motor Auditory Visual Education (SAVE) Program is an intervention that utilizes an accelerated multisensory integration process to facilitate neuroplasticity. This study aimed to determine if the SAVE Program might benefit individuals with residual symptoms from a prior concussion. Methods: The study consists of two 1-hour sessions per day for 5 consecutive days. Five individuals were recruited and completed a symptom questionnaire, static postural assessment, auditory detection assessment, peripheral vision assessment, and a battery of computerized cognitive tests. Results: Following the treatment program, 5 individuals showed significant (p < 0.05) improvements in various reported symptoms, significant (p < 0.05) improvements in recognizing colors further from the center of a target, and better detection of an auditory stimulus in the right ear. All tested cognitive domains improved, except for episodic memory accuracy and choice reaction time. The most notable improvements were in planning latency (29.94%), planning accuracy (19%), and working memory accuracy (34.30%). The results of the balance assessment were mixed. Conclusion: The results suggested that the SAVE Program may be a beneficial treatment of residual symptoms from a prior concussion. However, the intrinsic caveats of a case series require more rigorous research.

The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61–70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway.

This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3+) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.

OBJECTIVE Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen. MATERIALS AND METHODS A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis. RESULTS Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01). CONCLUSIONS Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.

Objectives The purpose of this study was to measure faculty performance of simulated spinal manipulation on a mannequin to help identify teaching standards. Methods We measured 3-dimensional transmitted loads using a force plate mounted in the table. Thrusts were delivered through a compliant, jointed mannequin by faculty members along predefined “listings” as taught in lumbopelvic technique courses. Results Eleven chiropractic faculty members participated, delivering 9 thrusts at 3 loads (light, moderate, and heavy) along 9 different prone and side-posture listings, totaling 81 thrusts per participant. Single-hand Gonstead-style thrusts had variability in magnitude across participants and loads: light thrusts averaged 365 N (95% confidence interval [CI] 327-402), moderate thrusts 454 N (421-487), and heavy thrusts 682 N (623-740). All faculty members could easily distinguish the loads within their performances, but there was some crossover of load levels between participants. Thrust rates averaged 3.55 N/ms (95% CI 3.29-3.82). The dominant vector of prone thrusts was in the z direction (vertically downward), but side-to-side and inferior-to-superior vector components occurred. Conclusion Faculty member performance of simulated spinal manipulation indicated that they are able to control the thrust magnitude and rate as well as direction. In this sample, there was significant variability in peak loads between participants, which needs to be considered in student learning standards. These findings may be useful in translating the understanding of force characteristics to the technique teaching lab.

Adequate nutrition is essential for growth in children with cystic fibrosis (CF). The new CF Foundation Clinical Practice Guidelines bring attention to monitoring macronutrient intake as well as total energy.Dietary intake of 75 preschool children with CF and pancreatic insufficiency was examined and compared to the Clinical Practice Guidelines. Regression analyses examined relationships between macronutrient intake and growth.Approximately 45% of children met the 110% minimum recommended dietary allowance (RDA) recommendation. Children consumed 35.3% (6.1) of total daily energy intake from fat, 12.7% (1.7) from protein, and 52.0% (6.1) from carbohydrates. Percent energy from protein was associated with height growth.Many preschoolers with CF are not meeting nutrition benchmarks for total energy and fat. To optimize nutrition early, dietary monitoring with frequent individualized feedback is needed. Optimizing intake of macronutrients that promote growth, especially fat and protein, should be a primary clinical target.

Study Objective To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature. Design Retrospective cohort study and review of literature (Canadian Task Force classification II-2). Setting Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill. Patients All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015. Interventions RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma. Measurements and Main Results Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement. Conclusion RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery.

// Li Sun 1, 3, * , Yajie Yin 1, 2, 3, * , Leslie H. Clark 3 , Wenchuan Sun 3 , Stephanie A. Sullivan 3 , Arthur-Quan Tran 3 , Jianjun Han 4 , Lu Zhang 1 , Hui Guo 1 , Esther Madugu 3 , Tommy Pan 3 , Amanda L. Jackson 5 , Joshua Kilgore 6 , Hannah M. Jones 3 , Timothy P. Gilliam 3 , Chunxiao Zhou 3, 7 and Victoria L. Bae-Jump 3, 7 1 Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China 2 School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China 3 Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 4 Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China 5 Division of Gynecologic Oncology, University of Cincinnati, Cincinnati, OH, USA 6 Houston Methodist Gynecologic Oncology Associates, Houston, TX, USA 7 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA * These authors have contributed equally to this work Correspondence to: Victoria L. Bae-Jump, email: victoria_baejump@med.unc.edu Chunxiao Zhou, email: czhou@med.unc.edu Keywords: glycolysis, glutaminolysis, ovarian cancer, AMPK/mTOR Received: April 19, 2017 Accepted: June 04, 2017 Published: June 29, 2017 ABSTRACT Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer.

Importance Endometrial cancer (EMCA) is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. Lymph node metastasis is the most significant prognostic factor in EMCA. Sentinel lymph node (SLN) mapping has become a well-accepted procedure in surgical oncology and may strike a balance between the risks and benefits of lymphadenectomy. Objective The aim of this study was to review the current literature regarding the history, techniques, and clinical application of SLN mapping in EMCA. Evidence acquisition Evidence was obtained through systematic literature review through PubMed and ClinicalTrials.gov. Conclusions Sentinel lymph node biopsy for EMCA is an accepted approach to the staging of this cancer; however, a consensus approach to the SLN biopsy technique and pathologic assessment is needed. Surgeons newly adopting the technique should proceed with caution and care to monitor outcomes.

Objective: To assess the force profiles of high-velocity low-amplitude thrusts delivered to a mannequin on a force platform by novice students given only verbal instructions. Methods: Student volunteers untrained in adjusting delivered a series of adjustments to a mannequin on a force platform. Participants performed 3 light, 3 normal, and 3 heavy thrusts on 5 listings specifying contact point, hand, and direction. Force profiles were analyzed for speed and amplitude, consistency, and force discrimination. Two recording sessions occurred 10 weeks apart. Results: Sixteen participants (11 females, 5 male) completed the study. Peak forces ranged from 880 to 202 N for heavy thrusts and 322- to 66 N for light thrusts. Thrust rate was from 8.1 to 1.8 Newtons per millisecond. Average coefficients of variability (CV = STD/mean) at each load level (initial/final) were heavy: 17%/15%; normal: 16%/15%; and light: 20%/20%, with 0 as ideal. A force ratio measured students' abilities to distinguish thrust magnitude. The heavy/normal ratio (initial/final) was 1.35/1.39, and the light/normal ratio was 0.70/0.67. Conclusions: At this point, without force feedback being used in the classroom, novice students can produce thrusts that look like those of their teachers and of experienced practitioners, but they may not produce similar speed and force values. They are consistent within and between sessions and can discriminate between light and heavy loads. A natural next step in our educational research will be to measure adjustment factors on more experienced cohorts of students with and without the presence of force-feedback training apparatus.

Significance Uterine carcinosarcoma (UCS) is an aggressive endometrial cancer variant distinguished from endometrial adenocarcinoma (EC) by admixed malignant epithelial and mesenchymal components (carcinoma and sarcoma). The molecular events underlying UCS are enigmatic, as cancer gene mutations are generally shared among UCS/EC. We take advantage of genetic approaches in mice to show that inactivation of Fbxw7 and Pten results in UCS through spontaneous acquisition of mutations in a third gene (Tp53), arguing for strong biological selection and synergism in UCS. We used this UCS model including tumor-derived cell lines to show that Fbxw7 loss drives epithelial–mesenchymal transition, explaining Fbxw7’s role in UCS. This model system argues that simultaneous genetic defects in 3 distinct pathways (Fbxw7, Pten/PI3K, Tp53) converge in UCS genesis., Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as Tp53 and Pten. However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor Fbxw7 in endometrial cancer through defined genetic model systems. Inactivation of Fbxw7 and Pten resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired Trp53 mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial–mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

Highlights • Uterine serous carcinoma is a high-risk endometrial cancer; adjuvant treatment in stage IA disease is controversial. • Patients with stage IA polyp-confined disease are inconsistently managed. • The impact of adjuvant treatment on recurrence outcomes for polyp-confined stage IA disease is unclear., Uterine serous carcinoma is a rare, high-risk histological subtype of endometrial cancer, and use of adjuvant treatment in early stage IA disease is inconsistent, especially when the tumor is confined entirely within an endometrial polyp. We herein present a case of extrauterine recurrence in a 67-year-old female with polyp-confined, stage IA uterine serous endometrial cancer. She underwent comprehensive surgical staging with the pathology returning a 5 cm uterine serous carcinoma confined completely to a 7 cm polyp with negative margins, negative myometrial and lymphovascular space invasion, and twenty-nine negative para-aortic and pelvic lymph nodes. She went on to complete six cycles of adjuvant carboplatin and paclitaxel. She presented with a new pleural effusion approximately 20 months after receiving definitive treatment, and a diagnosis of recurrent, metastatic uterine serous carcinoma was confirmed through cytology. A review of the literature suggests practice patterns involving adjuvant treatment for polyp-confined stage IA uterine serous carcinoma are highly variable. Prospective studies clarifying the utility of adjuvant treatment for polyp-confined disease in comprehensively staged patients, especially pertaining to the impact this pathology has on recurrence risk, are needed for these patients.

Objective To evaluate awareness and acceptability of population-based BRCA testing among an unselected population of women presenting for annual gynecologic health assessment, with secondary objective to determine if a racial disparity exists in acceptability and awareness of this screening strategy. Methods Women presenting for routine gynecologic care in an outpatient setting of a single academic institution were anonymously surveyed. Survey collected age, self-identified race and ethnicity, education level, personal and family history of breast and/or ovarian cancer (BOC), awareness and interest, and willingness to pay out of pocket for testing. Responses were compared with bivariate and multivariate analysis. Results Interest in testing was expressed in 150 of 301 (45.1%) of participants. Women with a family history of BOC were more likely to be interested in testing than those without (OR = 1.9 (1.0–3.6)). Interest in testing was associated willingness to pay (OR = 3.3 (1.7–6.4)). Higher education level was associated with awareness of testing (OR = 9.9 (2.0–49.7)). Interest in testing was similar between racial groups, but awareness and willingness to pay for testing were higher among White women. Multivariate analysis with adjustment for education level confirmed that Black and Hispanic women were less likely to have awareness of genetic testing compared to White women and non-Hispanic Women, respectively (OR = 0.11 (0.05–0.3); OR = 0.10 (0.01–0.8)). Conclusions Interest in genetic testing among women in the general population is high. Despite interest, awareness of BRCA is poor among Black and Hispanic women even when adjusting for education level.

Importance Women in low- and middle-income countries (LMICs) are responsible for the stability of their families. Child survival is directly linked to the health and well-being of their mother. Cancer is the leading cause of morbidity and mortality worldwide, and the incidence and mortality for women from cancer are projected to increase over the coming decades. Gynecologic cancer outcomes are improved when women are cared for by a gynecologic oncologist; however, there are limited specialized providers in LMICs. Increasing interest and involvement from specialists in the United States will improve partnerships abroad and the care of women worldwide. Objective To summarize the importance of global gynecologic oncology care and the current data for US trainees in obstetrics and gynecology to participate in clinical and capacity-building opportunities. Evidence acquisition We performed a PubMed literature search for articles pertaining to the topic of global health education in obstetrics and gynecology and gynecologic oncology specifically. Results Many obstetric and gynecologic residency programs offer international opportunities, but these are less than those in other specialties and are more frequently focused in obstetrics. Many gynecologic oncology fellowship programs offer international experiences for fellows; however, the time and resources required are limited. Several US and international programs are ongoing to improve capacity building for gynecologic oncology in LMICs with local trainees. Conclusions and relevance Training and care in gynecologic oncology care worldwide are improving through efforts at multiple levels. Continued efforts are needed to improve US trainee international education and experience.

Highlights • TP53 mutations are common in serous endometrial tumors. • Endometrial tumors with micro and macrometastasis are more likely than tumors with ITC only to have LVSI. • No patient with ITC only disease had a recurrence in the study time frame., Objectives Lymph node (LN) metastasis and genomic profiles are important prognostic factors in endometrial cancer (EMCA). However, the prognostic significance of low volume metastasis found in sentinel lymph nodes (SLN) is unknown. We sought to determine if genomic mutations were associated with metastatic volume. Methods Surgically staged women with EC who were enrolled in both a SLN clinical trial and tumor sequencing protocol were eligible. Relevant targets were enriched by a custom designed Agilent SureSelect hybrid capture enrichment library using standard protocols. Three specific gene mutations were evaluated, TP53, PTEN and PIK3CA in the primary tumor of patients with LN negative, LN positive and ITC disease. Results 42 patients were eligible; of these, 7 (16.7%) had ITC only and 7 (16.7%) had micrometastatic or macrometastatic (LN positive) disease. No differences were seen in TP53, PIK3CA or PTEN between groups. All ITC patients with TP53 mutations were of non-endometrioid histology (2/7). Deeper myometrial invasion and lymph vascular space invasion were more likely to occur in the LN positive group (p

Objective The purpose of this investigation was to examine treatment adherence to medication and lifestyle recommendations among pediatric migraine patients using electronic monitoring systems. Background Nonadherence to medical treatment is a significant public health concern, and can result in poorer treatment outcomes, decreased cost-effectiveness of medical care, and increased morbidity. No studies have systematically examined adherence to medication and lifestyle recommendations in adolescents with migraine outside of a clinical trial. Methods Participants included 56 adolescents ages 11-17 who were presenting for clinical care. All were diagnosed with migraine with or without aura or chronic migraine and had at least 4 headache days per month. Medication adherence was objectively measured using electronic monitoring systems (Medication Event Monitoring Systems technology) and daily, prospective self-report via personal electronic devices. Adherence to lifestyle recommendations of regular exercise, eating, and fluid intake were also assessed using daily self-report on personal electronic devices. Results Electronic monitoring indicates that adolescents adhere to their medication 75% of the time, which was significantly higher than self-reported rates of medication adherence (64%). Use of electronic monitoring of medication detected rates of adherence that were significantly higher for participants taking once daily medication (85%) versus participants taking twice daily medication (59%). Average reported adherence to lifestyle recommendations of consistent noncaffeinated fluid intake (M = 5 cups per day) was below recommended levels of a minimum of 8 cups per day. Participants on average also reported skipping 1 meal per week despite recommendations of consistently eating three meals per day. Conclusions Results suggest that intervention focused on adherence to preventive treatments (such as medication) and lifestyle recommendations may provide more optimal outcomes for children and adolescents with migraine and their families. Once daily dosing of medication may be preferred to twice daily medication for increased medication adherence among children and adolescents.

Highlights • Spontaneous bladder ruptures have only been reported intraperitoneally, and years after the cessation of therapy. • Extraperitoneal bladder rupture can occur with radiation therapy in treatment of cervical cancer. • Improved reporting of toxicity is needed to identify types of genitourinary toxicity seen with modern chemoradiation., The standard of care for locally advanced cervical cancer is pelvic radiotherapy with sensitizing cisplatin, and intracavitary brachytherapy. This standard of care treatment paradigm has best survival outcomes, however is associated with genitourinary toxicities. Spontaneous bladder rupture (SBR) is a rare complication of chemoradiation that has only been reported in literature as an intraperitoneal rupture occurring years after the cessation of treatment. We herein present a novel case of extraperitoneal SBR in a 27-year-old female with FIGO Stage IIIC cervical cancer and no prior surgical history who was undergoing chemoradiation with sensitizing cisplatin. During her final planned brachytherapy treatment upon instilling the bladder under ultrasound guidance, an anterior midline extraperitoneal rupture was noted. She was managed conservatively for several weeks and during this time was ultimately able to complete her external beam therapy and last cycle of cisplatin. After approximately ten weeks of conservative management, imaging demonstrated complete resolution of the rupture. A review of the literature suggests this complication tends to occur as an intraperitoneal rupture years after the cessation of therapy. Late genitourinary complications and types of complications are rarely reported in clinical trials, so it is difficult to determine the true incidence of rare complications and identify patients that may be at risk.

2067 Background: A patient’s understanding of surgery is often limited, especially in the setting of complex oncologic procedures. A recent review found that interventions such as the use of written materials, videos, and websites, improve patients’ knowledge of the procedure and their satisfaction with decision making. We sought to determine if a video-based approach in patients undergoing robotic endometrial cancer staging improves satisfaction with perioperative counseling. Secondary objectives were physician satisfaction, patient comprehension, and visit length. Methods: From 2018-2019, patients were randomized to standard physician education or multimedia-based education, which included watching two novel animated videos followed by focused physician counseling. Basic demographic information was collected. Patient satisfaction was assessed using the Client Satisfaction Questionnaire-8 (CSQ-8, a validated satisfaction survey, scored 8-32) and a global satisfaction score (10-point scale). Physician satisfaction was assessed using a global satisfaction score. Comprehension was assessed with a 9 question survey at 3 time points. Descriptive statistics were used to compare groups. Results: Of 76 patients randomized, the majority were Caucasian (68%), 50-70 years old (70%), and had at least some college education (75%). Most patients had undergone prior surgery (83%) and one fourth had a prior cancer diagnosis. Demographic variables and surgical history were similar between groups. The video patients reported higher satisfaction on the CSQ-8 (31.57 ± 1.02 vs 30.62 ± 2.09, p < 0.05) and global satisfaction score (9.95 ± 0.23 vs 9.74 ± 0.55, p < 0.05). There was no difference in comprehension scores between groups at either the initial or postoperative visit. At the time of surgery, comprehension scores were higher in the standard education group compared to the video group (p < 0.01). There was no difference in physician satisfaction between groups. Among the video group, there was improvement in physician satisfaction between the first and second half of patients enrolled (p < 0.05). There was no difference in visit length. Conclusions: While multimedia education improved patient satisfaction in the preoperative setting, this was not clinically significant. Provider satisfaction improved over time with the use of a video aid. Multimedia education may be implemented in perioperative counseling based on provider preference and consideration should be made for further study of satisfaction after the initial implementation period. Clinical trial information: NCT03899441.

Uterine serous carcinoma (USC) represents an aggressive histologic subtype of endometrial cancer. It is associated with a poor prognosis, and improved therapies for women battling USCs are greatly needed. ONC201 is an orally bioavailable, first-in-class small molecule that induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) independent of p53. ONC201 has demonstrated anti-tumorigenic activity in pre-clinical models of solid tumors through induction of apoptosis and inactivation of the AKT/MAPK pathways. Recent phase I and II clinical trials have shown that ONC201 is well tolerated and may have single agent activity in high grade glioma patients among others. We sought to determine the effects of ONC201 on cell proliferation in USC and identify the mechanisms by which ONC201 inhibits cell growth in this disease. ONC201 inhibited cell proliferation in a dose-dependent manner in ARK1, ARK2 and SPEC-2 cell lines. The anti-proliferative activity of ONC201 in ARK1 and SPEC-2 cells was associated with induction apoptosis independent of p53 via both a TRAIL mediated apoptotic pathway and a mitochondrial apoptosis pathway. Treatment with ONC201 resulted in significant reduction in adhesion and invasion as well as inhibition of the AKT and MAPK pathways. In addition, ONC201 markedly potentiated the anti-tumorigenic effects of paclitaxel in USC cells. Our results suggest that ONC201 has significant anti-proliferative and anti-metastatic effects in USC cells through both induction of apoptosis and inhibition of the AKT and MAPK pathways. ONC201 and paclitaxel are a promising therapeutic combination in USC cells. Thus, ONC201 should be evaluated as a single agent and as a therapeutic partner with paclitaxel in future clinical trials of USC.

Objective:We describe a change in teaching method from extended face-to-face instruction to a blended classroom environment in a research methods course and compare student scores following a change in assessment from mid-term examination to weekly quizzes.Methods:The course traditionally had been taught using a weekly 2-hour lecture for each academic term. A change in teaching methods was designed to include 20 minutes of lecture followed by 30 minutes of topic-specific in-class group discussions. The students then continued group work for an additional hour at an alternative location of their choice, such as the library, café, student study areas, or at home. Student homework/reading assignments were given as topics for weekly group discussions. In addition, the midterm examinations were replaced with weekly quizzes. Using t-test and analysis of variance, scores for four student cohorts in two successive academic terms were compared using identical multiple-choice questions from the midterms and quizzes for two topics. Student verbal feedback was elicited at the end of each term.Results:Quiz scores showed significant improvement over midterm scores for the more challenging statistics multiple-choice questions (t[371] = −2.21, p = .03, d = 0.23) with no significant improvement in multiple-choice questions about the safety of human subjects (t[374] = −.401, p = .69, d = 0.04). Student verbal feedback indicated higher satisfaction with the blended classroom and experiential learning style.Conclusion:Assessment using quizzes in an early and often format, instead of a midterm examination, was associated with higher scores on identical questions. Students preferred the blended classroom environment with experiential learning exercises and weekly quizzes.