Sacrospinous Hysteropexy Versus Prolapse Hysterectomy with Apical Fixation: A Retrospective Comparison over an 18 Year Period.

BACKGROUND: Pelvic organ prolapse (POP) is a common health problem, with a high lifetime risk for prolapse surgery. Uterine-preserving procedures such as vaginal sacrospinous hysteropexy (SSH) have become an increasingly utilized surgical option for the primary treatment of POP. We wanted to evaluate peri- and postoperative outcome parameters of SSH as an alternative to vaginal hysterectomy with apical fixation. METHODS: A retrospective cohort study was conducted (2003-2021). All patients who underwent primary SSH (study group) for symptomatic POP were matched 1:1 by age and BMI with patients who underwent primary prolapse hysterectomy with apical fixation (control group). RESULTS: A total of 192 patients were included with 96 patients in the each of the SSH and hysterectomy groups. There were no statistically significant differences in baseline characteristics. The SSH group show a significantly shorter mean surgery time (p < 0.001), significantly fewer hospitalization days (p < 0.001), and significantly less intraoperative blood loss (p = 0.033) in comparison to the control group. Neither group had any intraoperative complication, or an intraoperative conversion to other surgical management options. No statistically significant difference was found in postoperative complications as categorized by the Clavien-Dindo classification or in postoperative urogynecological issues (UTI, de-novo, incontinence, residual urine, voiding disorders). Through log regression, none of the confounding factors such as age, BMI, or preoperative POP-Q stage could be identified as independent risk factors for the occurrence of postoperative complications. CONCLUSIONS: Our results confirm that a uterus-preserving technique has many benefits and, thus, should be considered as an additional intermediate step in a long-term treatment plan of pelvic organ prolapse.

The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.

Staphylococcus aureus is an important human pathogen that can cause long-lasting persistent infections. The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response. So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host. Here, we used an experimental mouse model to investigate the host response to persistent S. aureus infection. Our results demonstrated that T cells, which are critical for controlling S. aureus infection, gradually lost their ability to respond to antigenic stimulation and entered a state of anergy with the progression of infection towards persistence. The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype. The presence of these anergic antigen-specific T cells may contribute to the failure of the host immune response to promote sterilizing immunity during persistent S. aureus infection and also offers new possibilities for novel immunotherapeutic approaches.

Staphylococcus aureus evades the extracellular antimicrobial activity of mast cells by promoting its own uptake.

In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5ß1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived and persisted by increasing the cell wall thickness and by gaining access into the mast cell cytosol. The expression of α-hemolysin was essential for staphylococci intracellular persistence. By hiding within the long-life mast cells, staphylococci not only avoid clearance but also establish an infection reservoir that could contribute to chronic carriage.

A glycoprotein M-deleted equid herpesvirus 4 is severely impaired in virus egress and cell-to-cell spread.

To analyse the function of the equid herpesvirus 4 (EHV-4) glycoprotein M homologue (gM), two different mutated viruses (E4DeltagM-GFP and E4DeltagM-w) were generated. Both gM-negative EHV-4-mutants were characterized on complementing and on non-complementing cells and compared with E4RgM, a virus where gM-expression had been repaired. It was demonstrated in virus growth kinetics that deleting gM had a more dramatic influence on EHV-4 replication than expected. Extracellular infectivity was detected 9-12 h later than in EHV-4-infected Vero cells and titres were reduced up to 2000-fold. In addition, mean maximal diameters of plaques were less than 20 % of diameters of wild-type plaques. These results are in contrast to most other alphaherpesviruses, including the closely related equid herpesvirus type 1, where deletion of gM only marginally influences the ability of viruses to replicate in cell culture. Nevertheless, analysis of infected cells by electron microscopy did not reveal a specific defect for deleting gM. It was concluded that EHV-4 gM is important for more than one step in virus replication in cell culture, influencing both efficient virus egress and cell-to-cell spread.