The vaginal microbiome is associated with endometrial cancer grade and histology.

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and ß diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and ß-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.

A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study.

BACKGROUND: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC). OBJECTIVE: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC. STUDY DESIGN: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate. RESULTS: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]). CONCLUSIONS: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies.

Changes in the Activity Measure for Post-Acute Care Domains in Persons With Stroke During the First Year After Discharge From Inpatient Rehabilitation.

OBJECTIVE: To describe functional changes after inpatient stroke rehabilitation using the Activity Measure for Post-Acute Care (AM-PAC), an assessment measure sensitive to change and with a low risk of ceiling effect. DESIGN: Retrospective, longitudinal cohort study. SETTING: Inpatient rehabilitation unit of an urban academic medical center. PARTICIPANTS: Among 433 patients with stroke admitted from 2012-2016, a total of 269 (62%) were included in our database and 89 of 269 patients (33.1%) discharged from inpatient stroke rehabilitation had complete data. Patients with and without complete data were very similar. The group had a mean age of 68.0±14.2 years, National Institutes of Health Stroke Score of 8.0±8.0, and rehabilitation length of stay of 14.7±7.4 days, with 84% having an ischemic stroke and 22.5% having a recurrent stroke. INTERVENTION: None. MAIN OUTCOME MEASURES: Changes in function across the first year after discharge (DC) were measured in a variety of ways. Continuous mean scores for the basic mobility (BM), daily activity (DA), and applied cognitive domains of the AM-PAC were calculated at and compared between inpatient DC and 6 (6M) and 12 months (12M) post DC. Categorical changes among individuals were classified as "improved," "unchanged," or "declined" between the 3 time points based on the minimal detectable change, (estimated) minimal clinically important difference, and a change ≥1 AM-PAC functional stage (FS). RESULTS: For the continuous analyses, the Friedman test was significant for all domains (P≤.002), with Wilcoxon signed-rank test significant for all domains from DC to 6M (all P<.001) but with no change in BM and DA between 6M and 12M (P>.60) and a decline in applied cognition (P=.002). Despite group improvements from DC to 6M, for categorical changes at an individual level 10%-20% declined and 50%-70% were unchanged. Despite insignificant group differences from 6M-12M, 15%-25% improved and 20%-30% declined in the BM and DA domains. CONCLUSIONS: Despite group gains from DC to 6M and an apparent "plateau" after 6M post stroke, there was substantial heterogeneity at an individual level. Our results underscore the need to consider individual-level outcomes when evaluating progress or outcomes in stroke rehabilitation.

Asbestos and ovarian cancer: examining the historical evidence.

Asbestos recently returned to the spotlight when Johnson & Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.

Feasibility of an Electromyography-Triggered Hand Robot for People After Chronic Stroke.

IMPORTANCE: Effective treatment of the affected hand after stroke is crucial for improved functional independence and recovery. OBJECTIVE: To determine the feasibility and clinical utility of an electromyography-triggered hand robot. DESIGN: Single-group repeated-measures design. Participants completed training 3×/wk for 6 wk. Feasibility data included participant feedback, adverse events, and compliance rates. Upper extremity outcomes were collected at baseline, discharge, and 6-wk follow-up. SETTING: Outpatient clinic. PARTICIPANTS: Twelve stroke survivors at least 6 mo poststroke living in the community. INTERVENTION: Eighteen sessions of intensive robotic hand therapy over 6 wk. Each 60-min treatment session was personalized to match the participant's ability. OUTCOMES AND MEASURES: Arm Motor Ability Test (AMAT), Stroke Impact Scale Hand subscale (SIS-H), Stroke Upper Limb Capacity Scale (SULCS), Fugl-Meyer Assessment, Box and Block Test, and dynamometer. RESULTS: All participants completed the training phase. Mild skin pinching or rubbing at dorsal proximal interphalangeal joint and proximal arm fatigue were the most common adverse events. Improvements in raw scores were achieved from baseline to discharge for all outcome measures, except the SULCS. Participants significantly improved from baseline to discharge on the AMAT and the SIS-H, and improvements were maintained at 6-wk follow-up. CONCLUSION AND RELEVANCE: Robotic hand training was feasible, safe, and well tolerated. Participants reported and demonstrated improvements in functional use of the affected arm. Thirty percent of participants achieved clinically significant improvements on the AMAT. We recommend further study of the device in a larger study using the AMAT as a primary outcome measure. WHAT THIS ARTICLE ADDS: It is feasible and safe to implement a robotic hand training protocol for people with moderate to severe arm impairment in an outpatient setting. Robotic training may provide a viable option for this group to actively participate in intensive training of the distal hand.

A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS).

OBJECTIVE: Up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. There are no effective adjuvant therapies for LMS. The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS). The primary endpoint of this study was a reduction in the recurrence rate for patients with this disease. METHODS: We performed a randomized, open-label, phase II study of letrozole (experimental arm) administered orally on a daily basis vs. observation (control) in patients with newly diagnosed early stage uLMS. Patient enrollment was to be open to any individual with newly diagnosed uLMS seen in the Gynecologic Oncology Center at M. D. Anderson Cancer Center. Hormone receptor positivity using CLIA approved lab testing was an eligibility requirement. No prior therapy was allowed. RESULTS: Nine patients were randomized. Four patients were in the experimental arm and five patients were in the observation arm. No patients had prior therapy. The median duration of protocol treatment was 43.9 months (range, 6.5-70.2). The median PFS for the experimental arm was not reached (NR) compared to 17.3 months. The percent progression free at 12 and 24 months was 100% for patients receiving letrozole compared to 80% at 12 months and 40% at 24 months for patients in the observation arm. CONCLUSIONS: While no definitive conclusions can be made due to early study closure, these early observations warrant further investigation. We desperately need an effective adjuvant therapy for women with early stage uLMS.

Association Between 2 Measures of Cognitive Instrumental Activities of Daily Living and Their Relation to the Montreal Cognitive Assessment in Persons With Stroke.

OBJECTIVES: To explore the relation between a computer adaptive functional cognitive questionnaire and a performance-based measure of cognitive instrumental activities of daily living (C-IADL) and to determine whether the Montreal Cognitive Assessment (MoCA) at admission can identify those with C-IADL difficulties at discharge. DESIGN: Prospective cohort study. SETTING: Acute inpatient rehabilitation unit of an academic medical center. PARTICIPANTS: Inpatients (N=148) with a diagnosis of stroke (mean age, 68y; median, 13d poststroke) who had mild cognitive and neurological deficits. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission cognitive status was assessed by the MoCA. C-IADL at discharge was assessed by the Executive Function Performance Test (EFPT) bill paying task and Activity Measure of Post-Acute Care (AM-PAC) Applied Cognition scale. RESULTS: Greater cognitive impairment on the MoCA was associated with more assistance on the EFPT bill paying task (ρ=-.63; P<.01) and AM-PAC Applied Cognition scale (ρ=-.43; P<.01). This relation was nonsignificant for higher MoCA scores and EFPT bill paying task scores. The AM-PAC Applied Cognition scale and the EFPT bill paying task had low agreement in classifying functional performance (Cohen's κ=.20). A receiver operating characteristic curve identified optimal MoCA cutoff scores of 20 and 21 for classifying EFPT bill paying task status and AM-PAC Applied Cognition scale status, respectively. For values above 20 and 21, sensitivity increased whereas specificity decreased for classifying functional deficits. Approximately one third of the participants demonstrated C-IADL deficits on at least 1 C-IADL measure at discharge despite having a MoCA score of ≥26 at admission. CONCLUSIONS: Questionnaire and performance-based methods of assessment appear to yield different estimates of C-IADL. Low MoCA scores (<20) are more likely to identify those with C-IADL deficits on the EFPT bill paying task. The results suggest that C-IADL should be assessed in those who have mild or no cognitive difficulties at admission.