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PURPOSE: Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests. EXPERIMENTAL DESIGN: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n = 66) and non-malignant conditions (n = 108), and global untargeted metabolomics was performed. Using the metabolite data (n = 920), we completed a multivariate biomarker discovery analysis. RESULTS: We analyzed grade 1/2 endometrioid carcinoma (n = 53) and other endometrial cancer subtypes (n = 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (P < 0.0001), tryptophan (P < 0.0001), and glutamate (P < 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q < 0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion. CONCLUSIONS: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis.

BACKGROUND: Patients presenting for gynecologic surgery are a heterogeneous group. Preoperative quality of life may be a useful tool to guide postoperative management. OBJECTIVE: This study aimed to examine the key drivers of preoperative quality of life to improve counseling and postoperative management. STUDY DESIGN: This study analyzed preoperative survey results from 154 participants using the following surveys: National Institutes of Health Toolbox Global Health v1.2, Gastrointestinal: Gas and Bloating v1.1 13a, Gastrointestinal: Diarrhea v1.0 6a, and Sexual Function and Satisfaction Brief Profile (Female) v2.0, Perceived Stress Scale, the Vaginal Assessment Scale, and the Vulvar Assessment Scale. Survey results in the form of T-scores were compared in patients with endometrial cancer and patients with benign gynecologic conditions using the Kruskal-Wallis test. The multivariate analysis was performed using linear regression to adjust the comparisons for age, body mass index, and comorbidity. RESULTS: Of the 154 patients, preoperative diagnosis was benign in 66% (n=102) and endometrial cancer in 34% (n=52). Patients with endometrial cancer were more likely to be older, non-White, in lower income brackets, have higher body mass index, and be postmenopausal (P.05), when adjusted for age, the differences in global health quality of life between patients with benign gynecologic conditions and those with endometrial cancer became significant, because the endometrial cancer group was older than the benign group (P.05). Sexual interest was decreased in the patients with endometrial cancer both in the unadjusted and adjusted model; and vulvar complaints became significantly different between the groups when controlling for body mass index, age, and comorbidities (P

ObjectiveThe objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions.MethodsData for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0-2) or poor (mRS score 3-6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0-1 comprised grade 1, 2-3 grade 2, and 4-5 grade 3.ResultsA total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).ConclusionsThe authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

Background: Our objective was to evaluate the effect of garden-based learning on outlook and behaviors toward vegetables among primarily Latinx students. An educational strategy, garden-based learning is a teaching tool that complements other disciplines. Methods: Third- and fourth-grade students at 4 elementary schools with different garden programs completed a bingo survey and participated in class discussions to measure outlook and behaviors toward vegetables. Results: Students in schools with more garden exposure were more likely to answer "Yes" to survey questions reflecting a positive attitude and behaviors toward vegetables. In class discussions, students most often mentioned vegetables grown in the school garden as their favorite vegetables. Conclusion: For third- and fourth-grade students, the length of exposure to a school garden appears to have a positive impact on both perceptions of and desire to consume vegetables. Other studies have shown that positive outlook and behaviors toward vegetables can change vegetable consumption habits in children. Integrating garden-based learning into the school curriculum may positively influence eating behaviors over the long-term future.

Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence score was constructed using baseline self-reported data regarding body size, diet, physical activity and alcohol consumption. Multivariable logistic regression demonstrated significantly reduced odds of having three or more adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95% confidence intervals [CI]: 0.46⁻0.99) and highly adherent (OR = 0.50, 95% CI: 0.31⁻0.81) participants compared to low adherers (p-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85⁻1.59, high adherence OR = 1.23, 95% CI: 0.85⁻1.79).

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P

Selenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D). The Selenium and Celecoxib (Sel/Cel) Trial was a randomized, placebo controlled trial of selenium 200 µg daily as selenized yeast and celecoxib 400 mg once daily, alone or together, for colorectal adenoma prevention. Men and women between age 40 and 80 years were eligible following colonoscopic removal of colorectal adenomas. The primary outcome was adenoma development. Celecoxib was suspended because of cardiovascular toxicity in other trials, but accrual continued to selenium and placebo. A total of 1621 participants were randomly assigned to selenium or placebo, of whom 1374 (84.8%) were available for analysis. All statistical tests were two-sided. In the respective placebo and selenium arms of 689 and 685 participants, adenoma detection after medians of 33.6 (range = 0.0-85.1 months) and 33.0 months (range = 0.0-82.6 months) were 42.8% and 44.1% (relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.91 to 1.16, P = .68). In participants with baseline advanced adenomas, adenoma recurrence was reduced by 18% with selenium (RR = 0.82, 95% CI = 0.71 to 0.96, P = .01). In participants receiving selenium, the hazard ratio for new-onset T2D was 1.25 (95% CI = 0.74 to 2.11, P = .41), with a statistically significantly increased risk of selenium-associated T2D among older participants (RR = 2.21; 95% CI = 1.04 to 4.67, P = .03). Overall, selenium did not prevent colorectal adenomas and showed only modest benefit in patients with baseline advanced adenomas. With limited benefit and similar increases in T2D to other trials, selenium is not recommended for preventing colorectal adenomas in selenium-replete individuals.

Aim: To determine whether differences in joint and tendon stiffness as measured by ultrasound shear wave elastography are present in breast cancer patients with aromatase inhibitor-associated arthralgias compared to age-comparable healthy control women. Methods: Postmenopausal women with stage I–III breast cancer who were taking adjuvant aromatase inhibitors and complained of joint pain were enrolled (n = 6). Postmenopausal women with no history of breast cancer, hormone treatment, or joint pain served as controls (n = 7). All subjects had bilateral hands and wrists evaluated by gray-scale and power Doppler ultrasound, and shear wave elastography ultrasound. Results: Patients with AI-associated arthralgias had significantly stiffer tendons than controls in the 1st extensor compartment (long axis; p = 0.001), 4th extensor compartment (long axis; p = 0.014), 3rd metacarpophalangeal joint (p = 0.002), the pooled values of the extensor compartments, both long (p = 0.044) and short axes (p = 0.035), and the pooled values for the metacarpophalangeal joints (p = 0.002). On ultrasound, the patients (but not controls) presented with hyperemia and increased tenosynovial fluid in the flexor and extensor tendon sheaths, and the median nerves were symptomatic and bifid; however, these differences were not statistically significant. Conclusions: This is the first study to identify increased tendon stiffness as a putative physiological characteristic of aromatase inhibitor–associated arthralgias. Future studies should determine whether increased tendon stiffness is a risk factor for the development of aromatase inhibitor–associated arthralgias, or a result of aromatase inhibitor treatment.

Background: A previous phase IB/II study of nab‐paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in 25 patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) demonstrated favorable results. This phase II study was conducted to further evaluate the safety, efficacy, and impact on quality of life (QOL) of NABPLAGEM in a multi‐center setting. Methods: Participants were ≥18 years; had measurable PDAC; Karnofsky performance status of ≥70%; life expectancy ≥12 weeks;

The National Diabetes Prevention Program (DPP) promotes lifestyle changes to prevent diabetes. However, only one-third of DPP participants achieve weight loss goals, and changes in diet are limited. Continuous glucose monitoring (CGM) has shown potential to raise awareness about the effects of diet and activity on glucose among people with diabetes, yet the feasibility of including CGM in behavioral interventions for people with prediabetes has not been explored. This study assessed the feasibility of adding a brief CGM intervention to the Arizona Cooperative Extension National DPP. Extension DPP participants were invited to participate in a single CGM-based education session and subsequent 10-day CGM wear period, during which participants reflected on diet and physical activity behaviors occurring prior to and after hyperglycemic events. Following the intervention, participants completed a CGM acceptability survey and participated in a focus group reflecting on facilitators and barriers to CGM use and its utility as a behavior change tool. A priori feasibility benchmarks included opt-in participation rates ≥ 50 % , education session attendance ≥ 80 % , acceptability scores ≥ 80 % , and greater advantages than disadvantages of CGM emerging from focus groups, as analyzed using the Key Point Summary (KPS) method. Thirty-five DPP members were invited to participate; 27 (77%) consented, and 24 of 27 (89%) attended the brief CGM education session. Median survey scores indicated high acceptability of CGM (median = 5 , range = 1 – 5), with nearly all (n = 23 / 24 , 96%) participants believing that CGM should be offered as part of the DPP. In focus groups, participants described how CGM helped them make behavior changes to improve their glucose (e.g., reduced portion sizes, increased activity around eating events, and meditation). In conclusion, adding a single CGM-based education session and 10-day CGM wear to the DPP was feasible and acceptable. Future research will establish the efficacy of adding CGM to the DPP on participant health outcomes and behaviors. [ABSTRACT FROM AUTHOR]

PurposeThe association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence.MethodsPooled analyses from two randomized, controlled trials included 1,730 participants who completed the Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma removed within 6 months of study registration, and had a follow-up colonoscopy during the trial. Logistic regression modeling was employed to estimate the effect of sedentary behavior, light-intensity physical activity, and moderate-vigorous physical activity on colorectal adenoma recurrence.ResultsNo statistically significant trends were found for any activity type and odds of colorectal adenoma recurrence in the pooled population. However, males with the highest levels of sedentary time experienced 47% higher odds of adenoma recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs) for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74), 1.41 (0.99, 2.01), and 1.47 (1.03, 2.11), respectively (p(trend) = 0.03). No similar association was observed for women.ConclusionsThis study suggests that sedentary behavior is associated with a higher risk of colorectal adenoma recurrence among men, providing evidence of detrimental effects of a sedentary lifestyle early in the carcinogenesis pathway.