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Objective: To characterise the bladder microbiota of continent adult women.Design: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data.Setting: US academic medical centre.Population: Well-characterised continent adult women.Methods: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing.Main Outcome Measures: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen).Results: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively.Conclusions: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged.Tweetable Abstract: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Urogynecology patients skew older and often require intimate exams to treat non-life-threatening conditions, thus making care particularly susceptible to the effects of COVID-19. We aim to understand COVID-19 vaccination attitudes amongst urogynecology patients during the pandemic, which has adversely affected healthcare delivery, to identify measures that can be undertaken to improve care going forward., Study Design: Cross-sectional surveys of urogynecology patients were conducted in three different states (Delaware, New Jersey, and Pennsylvania) between March and August 2021. Demographics, vaccination status, and COVID-19 attitudes were analyzed. Chi-square tests investigated group differences between vaccine-hesitant and unhesitant subjects., Results: Out of 158 surveys, eighty-three percent of respondents were vaccinated or planning to get vaccinated. Older age and regular flu vaccination predicted COVID-19 vaccination. Ninety-three percent of subjects were comfortable attending in-person visits. However, vaccine-hesitant individuals were less comfortable attending in-person and were significantly less likely to be comforted by clinic interventions, such as masking. Hesitant and unhesitant groups trusted doctors or medical professionals most for their source of COVID-19 information., Conclusions: Urogynecology patients mirror the general older population's COVID-19 vaccination attitudes, with distinct differences between hesitant and unhesitant groups. Vaccine-hesitant subjects appear less comfortable coming to in-person visits and less comforted by possible interventions, posing a difficult obstacle for clinics to overcome. High levels of patient trust suggest healthcare providers can play a crucial role in encouraging COVID-19 vaccination and combating misinformation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsThe primary author, Sean Spector, received assistance from Jessica Meehan (a non-affiliated research assistant) in manuscript preparation and writing. This assistance was in exchange for financial compensation from Sean Spector to Jessica Meehan., (© 2024 The Authors.)

In the development of therapeutic compounds that bind cell surface molecules, it is critical to demonstrate the extent to which the drug engages its target. For cell-associated targets, flow cytometry is well-suited to monitor drug-to-target engagement through receptor occupancy assays (ROA). The technology allows for the identification of specific cell subsets within heterogeneous populations and the detection of nonabundant cellular antigens. There are numerous challenges in the design, development, and implementation of robust ROA. Among the most difficult challenges are situations where there is receptor modulation or when the target-antigen is expressed at low levels. When the therapeutic molecules are bi-specific and bind multiple targets, these challenges are increased. This manuscript discusses the challenges and proposes best practices for designing, optimizing, and validating ROA., (© 2020 International Clinical Cytometry Society.)

Background: Prior to the advent of Oncotype DX 21-gene recurrence score (oDX) assay, the National Comprehensive Cancer Network (NCCN) guideline supported omission of adjuvant chemotherapy in patients with ≤ 1 cm (T1b) hormone receptor-positive (HR +), human epidermal growth factor receptor 2 (HER2-) node tumors. However, around 30% of these patients would have an oDX recurrence score that warrants consideration of adjuvant chemotherapy. To clarify the potential benefit of oDX in these patients, we performed a retrospective analysis comparing clinical outcomes of women with T1a or T1b, N0 HR + HER2- according to performance of oDX., Patients and Methods: After receiving institutional review board (IRB) approval, an institutional database was queried to identify patients with HR + HER2- ≤ T1bN0 tumors (n = 2307) diagnosed between 2009 and 2018. Patients were further stratified by recurrence score (RS) defined as low (< 18), intermediate (18-30), or high (> 30). Log-rank, Kaplan-Meier, and inverse probability of treatment weighting (IPW) analyses were used to compare disease-free survival (DFS) and overall survival (OS) across groups., Results: Performance of oDX (n = 1149, 49.8%) was associated with larger tumors, younger age, and White race. On univariate analysis, performance of oDX was associated with improved OS (P < 0.01). On multivariate IPW analysis, performance of oDX lengthened DFS by an average of 16.5 months, while OS was similar between groups (P < 0.01 and P = 0.73). The improved DFS was mainly driven by those with tumors ≥ T1b., Conclusions: Overall, outcomes were excellent regardless of oDX testing. Performance of oDX testing was associated with improved DFS in patients with tumors ≥ T1b. Our results support routine use of oDX testing in patients with tumors ≥ T1b.

Objective: To characterise the bladder microbiota of continent adult women., Design: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data., Setting: US academic medical centre., Population: Well-characterised continent adult women., Methods: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing., Main Outcome Measures: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen)., Results: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively., Conclusions: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged., Tweetable Abstract: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Purpose: The success of checkpoint blockade has led to a significant increase in the development of a broad range of immunomodulatory molecules for the treatment of cancer, including agonists against T-cell costimulatory receptors, such as OX40. Unlike checkpoint blockade, where complete and sustained receptor saturation may be required for maximal activity, the optimal dosing regimen and receptor occupancy for agonist agents is less well understood and requires further study., Experimental Design: We integrated both preclinical and clinical biomarker data sets centered on dose, exposure, receptor occupancy, receptor engagement, and downstream pharmacodynamic changes to model the optimal dose and schedule for the OX40 agonist antibody BMS-986178 alone and in combination with checkpoint blockade., Results: Administration of the ligand-blocking anti-mouse surrogate antibody OX40.23 or BMS-986178 as monotherapy or in combination with checkpoint blockade led to increased peripheral CD4 + and CD8 + T-cell activation in tumor-bearing mice and patients with solid tumors, respectively. OX40 receptor occupancy between 20% and 50% both in vitro and in vivo was associated with maximal enhancement of T-cell effector function by anti-OX40 treatment, whereas a receptor occupancy > 40% led to a profound loss in OX40 receptor expression, with clear implications for availability for repeat dosing., Conclusions: Our results highlight the value of an integrated translational approach applied during early clinical development to aggregate preclinical and clinical data in an effort to define the optimal dose and schedule for T-cell agonists in the clinic., (©2019 American Association for Cancer Research.)