Evaluation of Outcomes Between the Top-down Versus the Bottom-up Approach for Retropubic Midurethral Sling.

INTRODUCTION AND HYPOTHESIS: Retropubic midurethral sling (MUS) placement is the gold standard for the treatment of stress urinary incontinence in the USA. The procedure can be approached from either a top-down or a bottom-up direction, but there is a paucity of contemporary data regarding outcomes between these approaches. The aim of this study was to provide updated clinical outcomes data. METHODS: This was a retrospective cohort study of women undergoing the retropubic MUS procedure alone or at the time of pelvic organ prolapse repair between 2010 and 2020 at a single academic medical center. The electronic medical record was used to extract demographic data, operative approach, and perioperative complications. The primary outcome was a composite incidence of any perioperative complication. RESULTS: Of the 309 patients analyzed, 140 (45.3%) underwent top-down and 169 (54.7%) underwent bottom-up retropubic MUS placement. Patients undergoing top-down MUS placement were more likely to be older (mean age 58 vs 54, p=0.02), have a history of diabetes mellitus (20% vs 8.9%, p=0.004), and have had a prior hysterectomy (27% vs 16%, p=0.02). They were less likely to have a concurrent anterior (p<0.001) or posterior repair (p<0.001). Patients undergoing the top-down procedure were less likely to experience sling exposure (p=0.02); complications in the two groups were otherwise similar. CONCLUSIONS: The top-down approach to retropubic MUS placement was associated with lower rates of mesh erosion in this population of patients. Neither approach is associated with an increased overall risk of complications or de novo overactive bladder symptoms.

Immunogenicity of PE18, PE31, and PPE26 proteins from Mycobacterium tuberculosis in humans and mice.

Introduction: The large family of PE and PPE proteins accounts for as much as 10% of the genome of Mycobacterium tuberculosis. In this study, we explored the immunogenicity of three proteins from this family, PE18, PE31, and PPE26, in humans and mice. Methods: The investigation involved analyzing the immunoreactivity of the selected proteins using sera from TB patients, IGRA-positive household contacts, and IGRA-negative BCG vaccinated healthy donors from the TB endemic country Mozambique. Antigen-recall responses were examined in PBMC from these groups, including the evaluation of cellular responses in healthy unexposed individuals. Moreover, systemic priming and intranasal boosting with each protein, combined with the Quil-A adjuvant, were conducted in mice. Results: We found that all three proteins are immunoreactive with sera from TB patients, IGRA-positive household contacts, and IGRA-negative BCG vaccinated healthy controls. Likewise, antigen-recall responses were induced in PBMC from all groups, and the proteins stimulated proliferation of peripheral blood mononuclear cells from healthy unexposed individuals. In mice, all three antigens induced IgG antibody responses in sera and predominantly IgG, rather than IgA, responses in bronchoalveolar lavage. Additionally, CD4+ and CD8+ effector memory T cell responses were observed in the spleen, with PE18 demonstrating the ability to induce tissue-resident memory T cells in the lungs. Discussion: Having demonstrated immunogenicity in both humans and mice, the protective capacity of these antigens was evaluated by challenging immunized mice with low-dose aerosol of Mycobacterium tuberculosis H37Rv. The in vitro Mycobacterial Growth Inhibition Assay (MGIA) and assessment of viable bacteria in the lung did not demonstrate any ability of the vaccination protocol to reduce bacterial growth. We therefore concluded that these three specific PE/PPE proteins, while immunogenic in both humans and mice, were unable to confer protective immunity under these conditions.