Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the... Show moreManipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance. Show less
Moschovas, M.C.; Chew, C.; Bhat, S.; Sandri, M.; Rogers, T.; Dell'Oglio, P.; ... ; Patel, V. 2022
Background: The Oncotype DX assay is a clinically validated 17-gene genomic assay that provides a genomic prostate score (GPS; scale 0-100) measuring the heterogeneous nature of prostate tumors.... Show moreBackground: The Oncotype DX assay is a clinically validated 17-gene genomic assay that provides a genomic prostate score (GPS; scale 0-100) measuring the heterogeneous nature of prostate tumors. The test is performed on prostate tissue collected during biopsy. There is a lack of data on the association between the GPS and tumor pathology after radical prostatectomy (RP). Objective: To investigate the association between GPS and final pathology, including extra prostatic extension (EPE), positive surgical margin (PSM), and seminal vesicle invasion (SVI). Design, setting, and participants: Data for the 749 patients who underwent Oncotype DX assay and RP at a referral prostate cancer center between 2015 and 2019 were retrospectively assessed to evaluate the association between GPS and unfavorable pathology parameters. Intervention: After a GPS genetic test, patients underwent robotic RP performed by the same surgeon. Outcome measurement and statistical analysis: Multivariable logistic regression analyses were performed to assess the association between GPS and EPE, PSM, and SVI. The models were adjusted for age, clinical stage, prostate-specific antigen (PSA) level, Gleason score, and time between the genomic assay and surgery. The median time between Oncotype DX assay and surgery was 176 d (interquartile range [IQR] 141-226). The median age was 63 yr (IQR 58-68), median GPS was 29 (IQR 21-39), and median PSA was 5.7 ng/ml (IQR 4.6-7.7). In multivariable analyses assessing the odds ratio (OR) per 20-point change in GPS, GPS was an independent predictor of EPE (OR 1.8, 95% confidence interval [CI] 1.4-2.3) and SVI (OR 2.1, 95% CI 1.3-3.4). In addition, when patients were grouped by GPS quartile, the percentage of cases with EPE and SVI increased with the GPS quartile. Conclusions: We provide evidence that the Oncotype DX GPS is significantly associated with adverse pathology after RP. Specifically, the risk of EPE and SVI increases with the GPS. Therefore, use of the Oncotype DX GPS may help clinicians to improve preoperative patient counseling and develop surgical strategies for patients with a higher chance of EPE or unfavorable pathological features. Patient summary: We studied whether the score for a prostate genetic test was associated with prostate cancer pathology findings for patients who had their prostate removed. We found that the risk of prostate cancer spread outside the gland and to the seminal vesicle increases with higher test scores. These findings may help surgeons in counseling patients on surgical options for prostate cancer. (C) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
Purpose: Prediction of potency recovery following robot-assisted radical prostatectomy (RARP) is useful for better patient counseling and postoperative treatment strategies. In this study we... Show morePurpose: Prediction of potency recovery following robot-assisted radical prostatectomy (RARP) is useful for better patient counseling and postoperative treatment strategies. In this study we propose a preoperative and postoperative nomogram to predict postoperative potency recovery following RARP.Materials and Methods: Patients from development set (6,502) were selected to develop the nomograms, and patients in validation set (2,706) were used for validation. Cox regression models were fitted on the development cohort to predict potency recovery after RARP using as prognostic factors the covariates selected. Two nomograms were drawn using the regression coefficients of the preoperative and postoperative Cox models.Results: The discrimination ability of the preoperative model was evaluated on the development cohort using the receiver operator curves estimated at 3, 6, 12 and 24 months. The AUC at these time points was 0.726, 0.734, 0.754, and 0.778, respectively. The areas under the curve of the postoperative model at 3, 6, 12 and 24 months were 0.746, 0.756 and 0.777, and 0.801, respectively. Preoperative and postoperative predictive models were validated using a separate set of 2,706 patients. The AUCs of the preoperative model at 3, 6, 12 and 24 months were 0.789, 0.772, 0.768, and 0.778, respectively. The ROC curves of the postoperative model at 3, 6, 12 and 24 months with AUCs of 0.807, 0.797, 0.793 and 0.798, respectively. Along with age and preoperative sexual function, nerve-sparing technique determines the potency outcomes justifying better AUC for postoperative model vs the preoperative model.Conclusions: The above nomograms help us to predict with good accuracy the probability of potency recovery within 3, 6, 12 and 24 months following surgery taking into consideration preoperative and postoperative factors. This is a novel tool for the care giver to predict realistic expectation of potency outcomes to the patients, while preoperative and immediate postoperative counseling. Show less
