Glacial changes in sea level modulated millennial-scale variability of Southeast Asian autumn monsoon rainfall.

Most paleoclimate studies of Mainland Southeast Asia hydroclimate focus on the summer monsoon, with few studies investigating rainfall in other seasons. Here, we present a multiproxy stalagmite record (45,000 to 4,000 years) from central Vietnam, a region that receives most of its annual rainfall in autumn (September-November). We find evidence of a prolonged dry period spanning the last glacial maximum that is punctuated by an abrupt shift to wetter conditions during the deglaciation at ~14 ka. Paired with climate model simulations, we show that sea-level change drives autumn monsoon rainfall variability on glacial-orbital timescales. Consistent with the dry signal in the stalagmite record, climate model simulations reveal that lower glacial sea level exposes land in the Gulf of Tonkin and along the South China Shelf, reducing convection and moisture delivery to central Vietnam. When sea level rises and these landmasses flood at ~14 ka, moisture delivery to central Vietnam increases, causing an abrupt shift from dry to wet conditions. On millennial timescales, we find signatures of well-known Heinrich Stadials (HS) (dry conditions) and Dansgaard-Oeschger Events (wet conditions). Model simulations show that during the dry HS, changes in sea surface temperature related to meltwater forcing cause the formation of an anomalous anticyclone in the Western Pacific, which advects dry air across central Vietnam, decreasing autumn rainfall. Notably, sea level modulates the magnitude of millennial-scale dry and wet phases by muting dry events and enhancing wet events during periods of low sea level, highlighting the importance of this mechanism to autumn monsoon variability.

Caprini assessment utilization and impact on patient safety in gynecologic surgery.

PURPOSE: Postoperative venous thromboembolism (VTE) can potentially be associated with significant morbidity, mortality, and healthcare costs. The aim of this study was to determine the utilization of Caprini guideline indicated VTE in elective gynecologic surgery patients and its impact on postoperative VTE and bleeding complications. METHODS: This was a retrospective cohort study of elective gynecologic surgical procedures performed between January 1, 2016, and May 31, 2021. Two study cohorts were generated: (1) those who received and (2) those who did not receive VTE prophylaxis based on Caprini score risk stratification. Outcome measures were then compared between the study cohorts and included the development of a VTE up to 90-days postoperatively. Secondary outcome measures included postoperative bleeding events. RESULTS: A total of 5471 patients met inclusion criteria and the incidence of VTE up to 90 days postoperatively was 1.04%. Overall, 29.6% of gynecologic surgery patients received Caprini score-based guideline VTE prophylaxis. 39.2% of patients that met high-risk VTE criteria (Caprini > 5) received appropriate Caprini score-based prophylaxis. In multivariate regression analysis, the American Society of Anesthesiologists (ASA) score (OR 2.37, CI 1.27-4.45, p < 0.0001) and Caprini score (OR 1.13, CI 1.03-1.24, p = 0.008) predicted postoperatively VTE occurrence. Increasing Charlson comorbidity score (OR 1.39, CI 1.31-1.47, P < 0.001) ASA score (OR 1.36, CI 1.19-1.55, P < 0.001) and Caprini score (OR 1.10, CI 1.08-1.13, P < 0.001) were associated with increased odds of receiving appropriate inpatient VTE prophylaxis. CONCLUSION: While the overall incidence of VTE was low in this cohort, enhanced adherence to risk-based practice guidelines may provide more patient benefit than harm to postoperative gynecologic patients.

A New Carvotacetone Derivative from the Aerial Part of Sphaeranthus africanus.

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''R,3''R-dihydroxy-2''-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''R-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC50 values ranging from 128.9-274.3 µM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.

New Halogenated Flavonoids from Adenosma bracteosum and Vitex negundo and Their α-Glucosidase Inhibition.

Adenosma bracteosum and Vitex negundo are natural sources of methoxylated flavonoids. Little is known about the α-glucosidase inhibition of multi-methoxylated flavonoid derivatives. Eighteen natural flavonoids were isolated from A. bracteosum and V. negundo. Seven halogenated derivatives were synthesized. Their chemical structures were elucidated by extensive NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. All compounds were evaluated for their α-glucosidase inhibition. Most compounds showed good activity with IC50 values ranging from 16.7 to 421.8 µM. 6,8-Dibromocatechin was the most active compound with an IC50 value of 16.7 µM. A molecular docking study was conducted, indicating that those compounds are potent α-glucosidase inhibitors.

Surgical Science-Simbionix Robotic Hysterectomy Simulator: Validating a New Tool.

STUDY OBJECTIVE: To gather validity evidence for and determine acceptability of Surgical Science-Simbionix Hysterectomy Modules for the DaVinci Xi console simulation system (software; 3D Systems by Simbionix [now Surgical Science-Simbionix], Littleton, CO, and hardware; Intuitive Surgical, Inc., Sunnyvale, CA) and evaluate performance benchmarks between novice and experienced or expert surgeons. DESIGN: Prospective education study (Messick validity framework). SETTING: Multicenter, academic medical institutions. PARTICIPANTS: Residents, fellows, and faculty in obstetrics and gynecology were invited to participate at 3 institutions. Participants were categorized by experience level: fewer than 10 hysterectomies (novice), 10 to 50 hysterectomies (experienced), and more than 50 hysterectomies (expert). A total of 10 novice, 10 experienced, and 14 expert surgeons were included. INTERVENTIONS: Participants completed 4 simulator modules (ureter identification, bladder flap development, colpotomy, complete hysterectomy) and a qualitative survey. Simulator recordings were reviewed in duplicate by educators in minimally invasive gynecologic surgery using the Modified Global Evaluative Assessment of Robotic Skills (GEARS) rating scale. MEASUREMENTS AND MAIN RESULTS: Most participants felt that the simulator realistically simulated robotic hysterectomy (64.7%) and that feedback provided by the simulator was as or more helpful than feedback from previous simulators (88.2%) but less helpful than feedback provided in the operating room (73.5%). Participants felt that this simulator would be helpful for teaching junior residents. Simulator-generated metrics correlated with GEARS performance for the bladder flap and ureter identification modules in multiple domains including total movements and total time for completion. GEARS performance for the bladder flap module correlated with experience level (novice vs experienced/expert) in the domains of interest and total score but did not consistently correlate for the other procedural modules. Performance benchmarks were evaluated for the bladder flap module for each GEARS domain and total score. CONCLUSION: The modules were well received by participants of all experience levels. Individual simulation modules appear to better discriminate between novice and experienced/expert users than overall simulator performance. Based on these data and participant feedback, the use of individual modules in early residency education may be helpful for providing feedback and may ultimately serve as 1 component of determining readiness to perform robotic hysterectomy.

α-Glucosidase Inhibitory Cycloartanes from the Vietnamese Combretum quadrangulare.

Leaves of Combretum quadrangulare Kurz showed potent α-glucosidase inhibition. Two new cycloartane-type triterpenes, combretic acids D and E were isolated from the bioactive fraction. The chemical structures were determined using NMR and MS methods. Combretic acid D represents for the first cycloartane having a dihydrofuran ring in the side chain. Combretic acids D and E showed significant α-glucosidase inhibition, with IC50 values of 13.9 and 30.7 µM, respectively. Combretic acid D was determined to be a non-competitive type in the kinetic study. The docking study in combination with dynamic simulations of this compound provided the molecular understanding of α-glucosidase inhibition.

Cycloartane-type triterpenoids from the whole plants of Macrosolen bidoupensis.

One new cycloartane-type triterpenoid, named macrobidoupoic acid A (as an C-24 epimeric mixture, 4a, 4 b), together with three known ones (1-3), were clarified by different chromatography from the M. bidoupensis whole plants. Triterpenoids (1, 3 & 4) were detected for the first time from the Macrosolen genus. Chemical structures of them were illuminated using HR-ESI-MS, and NMR (1 D & 2 D) assessments. The cytotoxic properties of triterpenoids (3 & 4) were examined against two human cancer cell lines (A549, and RD) by MTT assay. As results shown, triterpenoids (3 & 4) possessed moderate cytotoxic activity against A549 and RD cancer cells (IC50 ranged from 5.44 to 39.52 µM).

Correcting the Fundamentals of Laparoscopic Surgery "Illusion of Validity" in Laparoscopic Vaginal Cuff Suturing.

STUDY OBJECTIVE: The "illusion of validity" is a cognitive bias in which the ability to interpret and predict surgical performance accurately is overestimated. To address this bias, we assessed participants comparing fundamentals of laparoscopic surgery (FLS) and non-FLS tasks with cadaveric vaginal cuff suturing to determine the most representative simulation task for laparoscopic vaginal cuff suturing. DESIGN: Validity (Messick framework) study comparing FLS and non-FLS tasks with cadaveric vaginal cuff suturing. SETTING: Simulation center cadaver laboratory. PARTICIPANTS: Obstetrics and gynecology residents (n = 21), minimally invasive gynecologic surgery fellows (n = 3), gynecologic surgical subspecialists (n = 4), general obstetrician/gynecologists (n = 10). INTERVENTIONS: Tasks included a simulated vaginal cuff (ipsilateral port placement), needle passage through a metal eyelet loop (contralateral and ipsilateral), and intracorporeal knot tying (contralateral and ipsilateral). Simulation task times were compared with the placement of the first cadaveric vaginal cuff suture time, as well as the in-person and blinded Global Operative Assessment of Laparoscopic Skills (GOALS) score ("relations to other variables" validity evidence). Statistical analyses included Spearman's test of correlation (continuous and ordinal variables) or Wilcoxon rank sum test (categoric variables). MEASUREMENTS AND MAIN RESULTS: There was a stronger association with cadaver cuff suturing time for simulated vaginal cuff suturing time (r = 0.73, p <.001) compared with FLS intracorporeal contralateral suturing time (r = 0.54, p <.001). Additional measures associated with cadaveric performance included subspecialty training (median: 82 vs 185 seconds, p = .002), number of total laparoscopic hysterectomies (r = -0.53, p <.001), number of laparoscopic cuff closures (r = -0.61, p <.001), number of simulated laparoscopic suturing experiences (r = -0.51, p <.001), and eyelet contralateral time (r = 0.52, p <.001). Strong agreement between the in-person and blinded GOALS (intraclass correlation coefficient = 0.80) supports response process evidence. Correlations of cadaver cuff time with in-person (Spearman's r = -0.84, p <.001) and blinded GOALS (r = -0.76, p <.001) supports relations to other variables evidence CONCLUSION: The weaker correlation between FLS suturing and cadaver cuff suturing compared with a simulated vaginal cuff model may lead to an "illusion of validity" for assessment in gynecology. Since gynecology specific validity evidence has not been well established for FLS, we recommend prioritizing the use of a simulated vaginal cuff suturing assessment in addition to FLS.

Factors Associated with Burnout and Frustration among Minimally Invasive Gynecologic Surgery Fellows.

STUDY OBJECTIVE: Determine the prevalence of burnout and frustration among participants currently completing a fellowship in minimally invasive gynecologic surgery (FMIGS). DESIGN: Cross-sectional survey. SETTING: An anonymous survey was distributed to fellows in November 2018. PARTICIPANTS: Current FMIGS fellows. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 57 of 83 (67.7%) FMIGS participants in American Association of Gynecologic Laparoscopists-accredited programs completed a survey regarding fellowship characteristics and experiences. Overall, 40 participants (70.2%) indicated that they were satisfied with their fellowship program experience. There were 33 participants (57.9%) who reported burnout, and 38 participants (66.7%) had experienced anxiety, depression, or extreme fatigue during the last month. Of those who reported burnout, 26 (76.5%) reported that they did not receive support from their fellowship program. Participants who experienced burnout were more likely to be in their second year (p = .003), spent less time per week doing scholarly activities (p = .048), and were less satisfied with their fellowship experience (p <.001). Participants who experienced anxiety, depression, or extreme fatigue had more cofellows in their program (p = .031), worked on average more hours per week (p = .020), and were more often required to practice obstetrics in their fellowship (p = .022). CONCLUSION: Burnout symptoms are common among physicians across multiple specialties. Our findings suggest that this issue is prevalent among FMIGS participants. In addition, there is a lack of access to emotional and psychologic support programs for fellows experiencing burnout. We hope that this study will prompt attention to this important topic by both individual programs and American Association of Gynecologic Laparoscopists as a society to increase awareness and access to resources and promote wellness for fellows.

Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam.

Bioactive-guided phytochemical investigation of Euphorbia antiquorum L. growing in Vietnam led to the isolation of five ent-atisanes, one seco-ent-atisane, and one lathyrane (ingol-type). The structures were elucidated as ent-1α,3α,16ß,17-tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylate (2), ent-atisane-3-oxo-16ß,17-acetonide (3), ent-3α-acetoxy-16ß,17-dihydroxyatisane (4), ent-16ß,17-dihydroxyatisane-3-one (5), calliterpenone (6), and ingol 12-acetate (7). Their chemical structures were unambiguously determined by analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry, as well as by comparison with literature data. Among them, 1 is a new compound while 2 is an ethylated artifact of ent-3,4-seco-4,16ß,17-trihydroxyatisane-3-carboxylic acid, a new compound. Isolates were evaluated for alpha-glucosidase inhibition. Compound 3 showed the most significant inhibitory activity against alpha-glucosidase with an IC50 value of 69.62 µM. Further study on mechanism underlying yeast alpha-glucosidase inhibition indicated that 3 could retard the enzyme function by noncompetitive.

Hyperthermic intraperitoneal chemotherapy for treating ovarian cancer.

ABSTRACT: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used for decades as a treatment for disseminated abdominal malignancies, including pseudomyxoma peritonei and peritoneal mesothelioma. HIPEC had been used to treat recurrent ovarian cancer only when curative options were lacking, but new data indicate that it may be suitable as a primary treatment for patients with late-stage epithelial ovarian cancer, increasing the recurrence-free time interval and improving quality of life. However, treatment can be challenging because of patient trauma from surgery, combined with the toxicity and high temperature of the chemotherapeutic agents. This article reviews HIPEC and its targeted intraoperative and postoperative management.

Survival outcomes in patients with cervical cancer treated with open versus robotic radical hysterectomy: Our surgical pathology interrogation.

OBJECTIVE: To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. METHODS: In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. RESULTS: A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40-4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76-5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). CONCLUSION: Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

Comparing survival outcomes between surgical and radiographic lymph node assessment in locally advanced cervical cancer: A propensity score-matched analysis.

OBJECTIVE: To investigate progression-free survival (PFS) and overall survival (OS) between women who underwent surgical versus radiographic assessment of pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN) prior to chemoradiation therapy for cervical cancer. METHODS: In this retrospective cohort analysis, patients with stage IB2 - IIIB squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who completed concurrent chemoradiation therapy (CCRT) between 2000 and 2017 from the Mayo Clinic Cancer Registry were identified. A 1:2 propensity score matching between surgical and imaging groups was performed and PFS and OS were compared between groups. RESULTS: 148 patients were identified and after propensity score matching, 35 from the surgical group and 70 from the imaging group were included in the analysis. There were no statistical differences in baseline characteristics between the 2 groups. The median follow-up time was 41 months (range 7-218) for the surgical group and 51.5 months (range 7-198) for the imaging group. Five-year PFS was 62.6% for the surgical group and 72.4% in imaging group (HR 1.11, 95% CI 0.54-2.30, p = 0.77). Five-year OS was 70.2% for the surgical group and 70.5% for the imaging group (HR 1.02, 95% CI 0.46-2.29, p = 0.96). FIGO stage, PALN metastasis, and parametrial involvement were found to be poor prognosticators for PFS and OS in univariate analysis. Only PALN metastasis significantly predicted unfavorable PFS (HR 2.76, 95% CI 1.23-6.18, p = 0.01) and OS (HR 3.46, 95% CI 1.40-8.55, p = 0.01) in multivariate analysis. There were no differences in locoregional recurrence and distant metastasis between the two groups (p = 0.33 and 0.59 respectively). CONCLUSION: Patients with cervical cancer who underwent radiographic assessment of PLN and PALN had comparable survival outcomes to surgical assessment.

Tumor-free margins and local recurrence in squamous cell carcinoma of the vulva.

OBJECTIVE: To investigate the relation of pathologic tumor-free margins and local recurrence in patients who underwent primary surgery for vulvar squamous cell carcinoma. METHODS: In this retrospective analysis, patients with stage I-III vulvar squamous cell carcinoma who underwent primary surgery between 2000 and 2018 were identified from the Mayo Clinic Cancer Registry. RESULTS: A total of 335 patients were included and divided into three groups according to tumor-free margins: group 1 (<3 mm, n = 32); group 2 (≥3 to <8 mm, n = 151); group 3 (≥8 mm, n = 152). The median follow-up time was 73 months (range 2-240). A total of 78 (23.3%) patients developed local recurrence. With the inverse propensity score weighing method adjusting baseline characters, margins <8 mm had inferior local control (HR 1.98, 95% CI 1.13-3.41). The 5-year local disease-free survival (DFS) was 48.2%, 81.5% and 84.6% for group 1, 2 and 3 respectively (p < 0.001). There were no differences in groin lymph nodes relapse (p = 0.850), distant metastases (p = 0.253), or disease-specific survival (DSS) (p = 0.289) among the three groups. Margins <8 mm, midline involvement, multifocal disease, precancerous lesions on margins and depth of invasion >1 mm were found to be poor prognosticators for local DFS in univariate analysis. Multifocal disease was the strongest predictor for local recurrence in multivariate analysis (HR 4.32, 95% CI 2.67-6.99). CONCLUSION: Patients undergoing primary surgery for vulvar squamous cell carcinoma with tumor free-margins <8 mm have a higher local recurrence rate.

Management and outcomes of primary vaginal Cancer.

OBJECTIVE: To analyze clinical characteristics and survival of patients with primary vaginal cancer. METHODS: Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. RESULTS: A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1-240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p < 0.001). Advanced stage, tumor size >4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p < 0.001). CONCLUSION: Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

Nervisides I-J: Unconventional Side-Chain-Bearing Cycloartane Glycosides from Nervilia concolor.

Two new cycloartane glycosides, nervisides I-J, were isolated from Nervilia concolor whole plants. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data. These cycloartanes comprised a stereogenic center at C-24, the R configuration of which was assigned based on DFT-NMR calculations and the subsequent DP4 probability score. These compounds were tested for cytotoxicity against K562 and MCF-7 tumor cell lines, revealing mild cytotoxic activity.

Use of the Limbs and Things Hysterectomy Model to Describe the Process for Establishing Validity.

STUDY OBJECTIVE: To demonstrate the process for establishing or refuting validity for the Limbs and Things hysterectomy model. DESIGN: Prospective study using Kane's framework for establishing validity (Canadian Task Force classification: II-2). SETTING: Total laparoscopic hysterectomy (TLH) assessments completed in the operating room (OR) and simulation at 3 academic medical centers. PARTICIPANTS: Obstetrics and gynecology residents (n = 26 postgraduate years 3-4), a gynecologic oncology fellow (postgraduate year 5), and a gynecology oncology attending. INTERVENTIONS: Participants were rated with the myTIPreport feedback application by nonblinded faculty in the OR after TLH. In-person, simulation-based assessments were provided by 2 faculty members blinded to experience level using myTIPreport and Global Operative Assessment of Laparoscopic Skills (GOALS). Videos of simulated TLHs were rated by 2 minimally invasive gynecology fellows. MEASUREMENTS AND MAIN RESULTS: OR scores for TLH steps were significantly higher than simulation assessments (p < .001) with "competent" marked more frequently in the OR. Number of robotic + conventional TLHs performed as primary surgeon was not significantly correlated with OR myTIPreport rating (Spearman r = .30, p = .14) but was significantly correlated with myTIPreport and GOALS in-person simulation ratings (Spearman r = .39-.58, p = .001-.04). Agreement between in-person simulation rater 1 and 2 myTIPreport assessments was 71.4% (weighted κ, .68; 95% confidence interval, .45-.90), and intraclass correlation for the GOALS overall assessment was .71 (95% confidence interval, .46-.85), indicating substantial agreement. Blinded video reviews showed similar agreement (73.1%) between raters but less correlation with experience (Spearman r = .32-.42, p = .11-.03) than in-person reviews. Using area under the receiver operating characteristic curve, mean score for the individual components of GOALS that best differentiated myTIPreport noncompetent and competent levels of performance was 4.3. Feedback acceptability and model realism were rated highly. CONCLUSION: The scoring and generalization validity inferences for Limbs and Things and myTIPreport are supported when global assessments of performance are evaluated but not for individual components of the assessment instruments.

Internet Use by Gynecologic Oncology Patients and Its Relationship with Anxiety.

This study describes the use of the Internet for health information research by patients attending a gynecologic oncology practice and examines the association between its use and anxiety. A self-administered survey assessed patients' demographic information and Internet use. The Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI) were administered concurrently. Of 212 patients who consented to the study, 98 (46%) had an appointment because of a cancer diagnosis. Of 199 respondents, 91 (46%) reported searching the Internet for information about their condition. Internet searching was unassociated with race/ethnicity and positively associated with education level, annual household income, and married/partnered civil status. Only 16% of the patients reported that a health-care provider recommended use of the Internet for research. Comparing patients who used the Internet for research with those who did not, the STAI state and trait anxiety scores were similar. The HADS anxiety subscale score was higher for those who used the Internet versus those who did not, which suggests heightened anxiety. Internet use for research is common in gynecologic oncology patients, and its use is associated with increased anxiety. Physicians can use this medium to educate patients about their disease, build trust, and alleviate fear.

Phase 2 trial of everolimus and letrozole in relapsed estrogen receptor-positive high-grade ovarian cancers.

OBJECTIVES: We report the results of a phase 2 clinical trial of the combination of everolimus and letrozole in patients with relapsed estrogen receptor-positive high-grade ovarian cancer. The trial's primary endpoint was the proportion of patients alive and progression-free after 12weeks of therapy with the combination of everolimus and letrozole. A 12-week PFS of 45% or greater was considered a positive result. The feasibility of generating patient-derived xenograft (PDX) models from biopsy specimens was also evaluated. METHODS: Eligibility criteria included relapsed estrogen receptor-positive ovarian, fallopian tube or primary peritoneal carcinomas with measurable disease, not previously treated with everolimus or AIs. Both platinum-resistant and sensitive tumors were included. Xenografts were created from image-guided tumor biopsies at baseline. Patients received oral everolimus 10mg daily and letrozole 2.5mg daily. RESULTS: Twenty patients were enrolled, 19 were evaluable. Nine out of 19 were alive, progression-free, and still on treatment at the 12week evaluation time-point (12-week PFS of 47%) with a median PFS of 3.9months (95% CI: 2.8-11.0). The median overall survival was 13.0months. Twelve patients (63%) experienced at least one grade 3 or worse adverse events. PDX tumor engraftment was feasible in the majority of patients (9 out of 17, 52.9%). CONCLUSIONS: The combination of everolimus and letrozole is associated with a promising 47% 12-week PFS rate in patients with ER-positive relapsed high-grade ovarian cancer with acceptable toxicity. PDX tumor models can be generated from biopsies of ovarian tumors.