This cohort study among patients undergoing major surgery defines the distribution of digitally measured daily step counts after major inpatient surgical procedures, assesses the accuracy of physician assessment and ordering of ambulation, and quantifies the association of digitally measured step count with postoperative length of stay in the hospital.
The risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.
Background: Low English fluency in large culturally diverse institutions may contribute to meager minority accrual. Our objective was to: 1) Assess knowledge of proper consenting procedures among the research team when consenting a low English fluency patient. 2) Assess the enrollment rate of participants in cancer therapeutic trials who identify a preferred language other than English. Methods: An anonymous web-based survey was distributed at a single institution to investigators, research staff and translator services to assess knowledge of consenting procedures. Patient enrollment data was retrieved from the clinical trials enrollment tracking system from January 2011 -October 2014 and matched to registration data indicating preferred language (N = 1521). The number and type of cancer cases from January 2011-October 2014 were retrieved from the institutional cancer registry and matched to registration data indicating preferred language. Results: Although there are many organizational in-person and web-based trainings focused on the requirements for consenting low English fluency patients, members of the research team responded correctly to only 64.8% (σ = 24.6%) of the knowledge-based portion of the survey. Of the 12,538 index cancer cases indentified, 10% preferred a language other than English. Trial enrollment rates for cancer clinical trials were similar for English (13%), Spanish (11%), and, Armenian (10%) speakers. Populations speaking Russian and Arabic had the lowest participation at 5% each. Conclusions: In order to increase enrollment into clinical trials, institutions must explore more effective training opportunities for research staff, engage interpreters and adopt recruitment and study materials in different languages.
The human fallopian tube harbors the cell-of-origin for the majority of high-grade serous 'ovarian' cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We performed single-cell transcriptomic profiling in 12 primary fallopian specimens from 8 patients, analyzing around 53,000 individual cells to map the major immune, fibroblastic and epithelial cell types present in this organ. We identified 10 epithelial sub-populations, characterized by diverse transcriptional programs including SOX17 (enriched in secretory epithelial cells), TTF3 and RFX3 (enriched in ciliated cells) and NR2F2 (enriched in early, partially differentiated secretory cells). Based on transcriptional signatures, we reconstructed a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3 high intermediate. Computational deconvolution of the cellular composition of advanced HGSCs based on epithelial subset signatures identified the 'early secretory' population as a likely precursor state for the majority of HGSCs. The signature of this rare population of cells comprised both epithelial (EPCAM, KRT) and mesenchymal (THY1, ACTA2) features, and was enriched in mesenchymal-type HGSCs (P = 6.7 x 10 -27 ), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.
Objective To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer. Methods Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3–6 and as maintenance monotherapy in cycles 7–34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival. Results An interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual. Conclusions The addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.
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