Abdominal Mesh Colpopexy Without Promontory Fixation: 10-Year Follow-up Results of the Peritoneocolpopexy Technique.

OBJECTIVE: To restore apical vaginal prolapse support when the access to the promontory is challenging, a modified method of colpopexy may be needed. We present our 10-year results on the peritoneocolpopexy (PCP) technique without promontory fixation relying on unidirectional barbed delayed absorbable sutures (V-Loc). METHODS: Fourteen women who underwent PCP for vaginal vault prolapse between 2011 and 2014 participated in an IRB-approved prospective study (11 noninfected; 3 with infected mesh needing excision). Ten-year follow-up data including validated questionnaires (Urinary Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire-7 (IIQ-7), QoL), pelvic organ prolapse quantifications (POP-Q), complications, reoperations, and secondary prolapses were collected. Paired statistical analyses compared various timepoints and mixed model analysis assessed questionnaire and POP-Q trends over time. RESULTS: Median follow-up was 9.7years (interquartile range (IQR): 6.0-0.7) to last POP-Q and 10.4years (IQR: 9.6-11.5) to last contact. No patients were lost to follow-up. Mean baseline C point for all patients was -4.3 and -2.9; 1-year C point was -9.1 and -9.2 and -8.6 and -8.5, respectively at last visit. POP-Q findings improved between pre-PCP and 1-year post surgery and did not significantly change until the last visit. Trends in UDI-6, IIQ-7, QoL, and POP-Q findings showed no significant change in any category per year (95% confidence interval (CI), P=.2-.9). Secondary anterior compartment prolapse was noted in 3 patients with 1 requiring a repair. CONCLUSION: PCP provides durable vaginal apical support when access to the promontory is compromised. PCP can also be used to prevent secondary prolapse after an infected mesh removal.

Systematic Review of the Global Use of Validated Questionnaires in the Management of Stress Urinary Incontinence in Women.

INTRODUCTION: Our goal was to systematically review the most commonly used validated questionnaires in recent global literature on stress urinary incontinence (SUI) treatment. METHODS: PubMed, Embase, and Ovid databases were queried for manuscripts containing "female stress urinary incontinence" AND "diagnosis" AND "treatment" AND "questionnaire." Two independent reviewers screened studies for randomized controlled trials, prospective, and retrospective studies between 2018 and 2023. Exclusion criteria included male participants, non-SUI incontinence, and articles not originally written in English. The review was registered in PROSPERO [465721] and conformed to PRISMA guidelines. RESULTS: In 117 manuscripts meeting study criteria, the median of the mean ages was 52 years, with a median of 164 participants per study. Most studies originated in Europe (59/117). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was the most frequently used (52%), followed by the Patient Global Impression of Improvement (31%), the Urinary Distress Inventory 6 Short Form (25%), the Incontinence Quality of Life (20%), and the Incontinence Impact Questionnaire-Short Form (19%). These leading questionnaires were short, translated into several languages, and globally addressed important SUI-related domains, including the presence and severity of SUI, additional lower urinary tract symptoms, and the impact of SUI on quality of life, as well as changes perceived after treatment. CONCLUSIONS: This systematic review of the validated questionnaires used in contemporary SUI management literature could help guide recommendations for incorporating these favored instruments into future SUI treatment outcome documents.

Systematic Review of the Global Literature on Uncomplicated Recurrent Urinary Tract Infections in Women: Underscoring Major Heterogeneity.

OBJECTIVE: To examine the global literature database on uncomplicated recurrent urinary tract infections (rUTI), this systematic review assesses the availability of rUTI data based on geographic region and elucidates the current state of research and gaps in knowledge. METHODS: The databases PubMed, Embase, WHO Global Index Medicus, and SciELO were searched for keywords related to rUTI between 2000 and 2023. Three independent reviewers screened studies restricted to female participants age ≥18 years with uncomplicated rUTIs. Studies were excluded if they did not provide a definition for rUTI or did not cite or report an estimate for rUTI prevalence. The review was registered in PROSPERO and conformed to PRISMA guidelines. RESULTS: The search yielded 2947 studies of which 124 were ultimately included. Convenience samples were used for 91% of studies and sample sizes were 30% n <50, 29% n = 50-99, 22% n = 100-199, 36% n ≥200. Most studies were conducted in Europe (41%) or North America (39%), were prospective (52%), at tertiary centers (49%) and included all ages ≥18 (60%). The most common definition for rUTI was 2 UTI/6 m or 3 UTI/1y (62%). Regardless of study location, most studies cited prevalence estimates for rUTI derived from U.S.-based populations. CONCLUSION: This study represents the first formal investigation of the global literature base on uncomplicated rUTI. Studies on rUTIs are globally of small scale and definitions used for rUTI are heterogeneous. More studies are needed to ascertain the true prevalence of rUTI outside of North America and Europe.

Daily and Weekly Urine Variations in Bacterial Growth Susceptibility in Postmenopausal Women With no History of Urinary Tract Infection: A Pilot Study.

OBJECTIVE: To evaluate bacterial growth in the bladder as a major virulence factor during urinary tract infections (UTIs), we assessed the variability of uropathogenic bacterial growth in urine samples over multiple timepoints from 3 postmenopausal women with no history of UTI. METHODS: Following IRB approval, postmenopausal women who never had a UTI provided mid-stream urine samples 3 times daily (8 a.m., 12 p.m., and 4 p.m.), twice a week over 2 weeks, as well as dietary intake logs. Each sample was studied for pH and bacterial growth using 3 uropathogenic Escherichia coli (E.coli) strains (LRPF007, KE40, UTI89), 1 uropathogenic Enterococcus faecalis strain (HRH40), and 1 non-pathogenic E. coli strain (W3110). RESULTS: Similar mean growth yields were observed for the uropathogenic strains (mean ∆OD600 =0.1-0.13) with high variability (standard deviation [SD]= 0.12-0.28) and lower mean growth for the non-pathogenic strain (mean ∆OD600 =0.05). Urine from each individual at different collection times never had the same bacterial growth potential for any bacterial strain. There were significant associations between urine pH decrease with higher fat (P = .017), vitamin D (P = .02), magnesium (P = .049), fluid (P = .013), and ash (P = .01) intake. CONCLUSION: Major variations were observed in the bacterial growth response in the urine of the same individuals. These variations imply a requirement for a normalization procedure, eg, growth in synthetic urine, for analysis of bacterial growth in urine. There were significant associations between decreased urine pH and several nutrients found in foods that are classified as highly acidic.

Development and Evaluation of an Immunoinformatics-Based Multi-Peptide Vaccine against Acinetobacter baumannii Infection.

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens.

Characteristics of Nationwide Urinary Tract Infection (UTI) Visits by Age and Type II Diabetes Status in Women.

Background Through a national database search of office visits, we studied the contribution of two known risk factors for urinary tract infections (UTIs) in women: age and type 2 diabetes mellitus (T2DM). Methodology The National Ambulatory Medical Care Survey (NAMCS) database was queried for visits including a UTI diagnosis and a urine culture order. Data were included for all visits involving adult women for available years, 2014-2016 and 2018. Data on demographics, reason for visit, T2DM status, UTI workup, and UTI treatment were collected. Patients with Alzheimer's disease or chronic kidney disease were excluded. Descriptive statistics were displayed as weighted means with standard errors for continuous variables. The effect of age was compared based on a 65-year-old cutoff. Results One hundred sixty-seven surveyed visits were analyzed for the years 2014-2016 and 2018, representing an estimated 7.4 million visits nationwide. Women ≥65 years were more likely to be white, non-Hispanic/non-Latino, from the Midwest or West, from metropolitan areas, and on Medicare/Medicaid than their younger counterparts. T2DM and urinalysis rates did not significantly vary between the two age groups (7.7% vs. 14.6%, P = 0.3; 78% vs. 76%, P = 0.9, respectively). For urinalysis rates between patients with and without T2DM, there was no significant difference in the <65-year-old group (80% vs. 78%, P = 0.9) or the ≥65-year-old group (93% vs. 73%, P = 0.12). Antibiotic prescription rates were also similar for T2DM and non-T2DM patients (67% vs. 75%, P = 0.7). Conclusions Through a national database analysis, we reported the demographic and visit differences aged <65 years and ≥65 years who sought care for UTIs in the United States over a four-year period. T2DM rates and urinalysis did not vary between age groups, and urinalysis rates and antibiotic prescription rates did not vary between T2DM and non-T2DM groups in an age-dependent matter. More research is needed to understand the demographic makeup and risk factors of UTI patients across the nation.

Hemorrhage Occluder™ Pin to control life-threatening bleeding during the removal of an infected sacrocolpopexy mesh: A case report.

Vaginal mesh exposures and infections are recognized complications of open and laparoscopic sacrocolpopexy performed for vault prolapse. In severe cases, complete sacrocolpopexy mesh removal may be necessary. This case report presents a 72-year-old woman with previous mesh sacrocolpopexy who presented with infected mesh and recurrent vaginal bleeding despite multiple attempts at surgical transvaginal mesh excision. A life-threatening massive hemorrhage occurred intra-operatively. After several failed attempts to control bleeding, hemorrhage Occluder™ Pins were successfully placed by vascular surgery to control presacral veins. Although an exceedingly rare complication, anticipation and rapid management of life-threatening bleeding are critical to save life during complicated mesh removals.

Isotyping and quantitation of the humoral immune response to SARS-CoV-2.

Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS-CoV-2 positive plasma samples tested exhibited significant neutralization capacity using a surrogate virus neutralization assay. Of the IgG subclasses, IgG1 and IgG3 exhibited the highest viral neutralization capacity; whereas, IgG2 and IgG4 viral neutralization was not observed. Comparison of SARS-CoV-2 elicited total IgG binding to emerging variant (alpha, beta, and delta) RBDs indicated decreased binding. Furthermore, neutralization by SARS-CoV-2 convalescent plasma of delta and omicron variant RBDs was significantly decreased suggesting that neutralizing antibodies in convalescent plasma are less effective in inhibiting variants currently in circulation.

Thioredoxin-mediated alteration of protein content and cytotoxicity of Acinetobacter baumannii outer membrane vesicles.

Acinetobacter baumannii is a Gram-negative bacterium responsible for many hospital-acquired infections including ventilator-associated pneumonia and sepsis. We have previously identified A. baumannii thioredoxin A protein (TrxA) as a virulence factor with a multitude of functions including reduction of protein disulfides. TrxA plays an important role in resistance to oxidative stress facilitating host immune evasion in part by alteration of type IV pili and cell surface hydrophobicity. Other virulence factors such as outer membrane vesicles (OMV) shed by bacteria have been shown to mediate bacterial intercellular communication and modulate host immune response. To investigate whether OMVs can be modulated by TrxA, we isolated OMVs from wild type (WT) and TrxA-deficient (ΔtrxA) A. baumannii clinical isolate Ci79 and carried out a functional and proteomic comparison. Despite attenuation of ΔtrxA in a mouse challenge model, pulmonary inoculation of ΔtrxA OMVs resulted in increased lung permeability compared to WT OMVs. Furthermore, ΔtrxA OMVs induced more J774 macrophage-like cell death than WT OMVs. This ΔtrxA OMV-mediated cell death was abrogated when cells were incubated with protease-K-treated OMVs suggesting OMV proteins were responsible for cytotoxicity. We therefore compared WT and mutant OMV proteins using proteomic analysis. We observed that up-regulated and unique ΔtrxA OMV proteins consisted of many membrane bound proteins involved in small molecule transport as well as proteolytic activity. Bacterial OmpA, metalloprotease, and fimbrial protein have been shown to enhance mammalian cell apoptosis through various mechanisms. Differential packaging of these proteins in ΔtrxA OMVs may contribute to the increased cytotoxicity observed in this study.

Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth.

Acetyl-CoA is a vitally important and versatile metabolite used for many cellular processes including fatty acid synthesis, ATP production, and protein acetylation. Recent studies have shown that cancer cells upregulate acetyl-CoA synthetase 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in response to stresses such as low nutrient availability and hypoxia. Stressed cancer cells use ACSS2 as a means to exploit acetate as an alternative nutrient source. Genetic depletion of ACSS2 in tumors inhibits the growth of a wide variety of cancers. However, there are no studies on the use of an ACSS2 inhibitor to block tumor growth. In this study, we synthesized a small-molecule inhibitor that acts as a transition-state mimetic to block ACSS2 activity in vitro and in vivo. Pharmacologic inhibition of ACSS2 as a single agent impaired breast tumor growth. Collectively, our findings suggest that targeting ACSS2 may be an effective therapeutic approach for the treatment of patients with breast cancer. SIGNIFICANCE: These findings suggest that targeting acetate metabolism through ACSS2 inhibitors has the potential to safely and effectively treat a wide range of patients with cancer.