Prolonged second stage effect on pelvic floor dysfunction: a follow up survey to a randomized controlled trial.

BACKGROUND: Pelvic floor dysfunction is a group of disorders that can significantly impact quality of life due to persistent urinary and anal incontinence. Data evaluating the effect of prolonged second stage of labor and postpartum pelvic floor dysfunction is heterogenous and limited. OBJECTIVE: To evaluate whether extending the length of labor in nulliparous women with prolonged second stage affects the presence of self-reported pelvic floor dysfunction after a randomized controlled trial of prolonged second stage. STUDY DESIGN: We conducted a planned follow up survey to our randomized controlled trial of prolonged second stage of labor using the Pelvic Floor Distress Inventory-20 (PFDI-20). The primary outcome was the PFDI-20 summary score. Secondary outcomes included urinary and fecal incontinence, prolapse, and patient satisfaction. Women surveyed were nulliparous patients with epidural anesthesia, previously enrolled in a randomized controlled trial that assigned them to extended labor, at least 1 additional hour in the second stage if they were undelivered after three hours, or to usual labor, defined as expedited delivery after three hours in the second stage. Women were surveyed at 12 - 36 months postpartum. RESULTS: Thirty-four of the seventy-eight women responded to the survey (43.6%). 17 women (50.0%) were from the extended labor group and 17 from the usual labor group (50.0%). Maternal demographic data were not significantly different between groups. The PFDI-20 summary score was 13.8 ± 23.3 in the extended labor group and 13.1 ± 20.9 in the usual labor group (p = 0.9). The Pelvic Organ Prolapse Distress Inventory-6 was 1.2 ± 2.9 in the extended labor group and 2.7 ± 6.4 in the usual labor group (p = 0.4). The Colorectal-Anal Distress Inventory-8 was 0.8 ± 2.8 in the extended labor group and 2.1 ± 4.0 in the usual labor group (p = 0.6). The Urinary Distress Inventory-6 was 11.8 ± 21.1 in the extended labor group and 8.3 ± 14.5 in the usual labor group (p = 0.6). Maternal and neonatal outcomes, as well as patient satisfaction, were not statistically significantly different between groups. CONCLUSION: Extending the length of labor in nulliparas with singleton gestations, epidural anesthesia, and prolonged second stage did not have an impact on PFDI-20 scores at 12-36 months postpartum. However, our study was underpowered to detect small, but potentially clinically important, differences. CLINICAL TRIAL NUMBER: NCT02101515 (Study Registration Date March 28, 2014) https://clinicaltrials.gov/ct2/show/NCT02101515.

Clinical Characteristics and Histologic Features of Hysterectomy Specimens From Transmasculine Individuals.

OBJECTIVE: To describe the clinical characteristics of transmasculine individuals who underwent hysterectomy and characterize surgical pathology findings. METHODS: Under an institutional review board-approved protocol, transmasculine individuals who were undergoing hysterectomy and bilateral salpingectomy or bilateral salpingo-oophorectomy were retrospectively identified from a single institution. Past medical, surgical, obstetric, and gynecologic history were collected, including prior testosterone use, cervical cancer screening status, and preoperative pelvic imaging. Surgical pathologic findings of the endometrium, ovaries, and cervix were collected. RESULTS: A total of 72 individuals were included. The median age was 30 years (range 19-51). The majority of patients had private insurance (n=53, 74%) and were on testosterone at time of the preoperative visit (n=63, 88%). Forty-two patients (58%) reported anxiety, depression, or bipolar disorder, and 34 patients (47%) were taking an antidepressant or mood stabilizer. Of the 68 patients eligible for cervical cancer screening, 33 (49%) were up to date before their surgical consultation visits. Pelvic pain was the leading indication for surgery (n=65, 90%), and 29 patients (40%) had multiple listed indications for surgery. Surgical pathology results included cervical intraepithelial neoplasia 2-3 in three patients (4%), endometrial or cervical atrophy in 13 patients (18%), and ovarian or paratubal cysts in 16 patients (22%). CONCLUSION: This study describes the distinct clinical characteristics and surgical pathology findings that health care professionals should consider when caring for this unique patient population, including a relatively high rate of mental health conditions, pelvic pain as the leading indication for surgery, and the presence of endometrial or cervical atrophy and ovarian or paratubal cysts on surgical pathology.

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.

The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however, the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3(+) NK cells. Further analysis showed that KIR2DL1(+) NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3(+) NK cells. KIR2DL1-3(+) NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-γ and TNF-α production. These results identify a novel relationship between HLA-C and KIR2DL(+) NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection.

Tumor necrosis factor α is associated with viral control and early disease progression in patients with HIV type 1 infection.

Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins with early disease progression. High plasma tumor necrosis factor α (TNF-α) levels (≥8.5 pg/mL) were significantly associated with an increased viral load set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3) and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T-cell count of <500 cells/mm(3) in the group with high TNF-α levels was driven by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF-α appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression.