Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

PURPOSE: Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of PNST in cancer predisposition syndrome NF1. EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 NF1 patients and 21 healthy controls and underwent whole genome sequencing. We investigated diagnosis-specific signatures of copy number alterations (CNA) with in silico size selection as well as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end-motifs, and fragment non-negative matrix factorization (NMF) signatures. RESULTS: The novel cohort of NF1 patients validated that our previous cfDNA CNA-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. CONCLUSIONS: Novel cfDNA fragmentomic signatures distinguish atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 and provides a blueprint for de-centralizing non-invasive cancer surveillance in hereditary cancer syndromes.

Dynamic Changes of the Genital Hiatus at the Time of Prolapse Surgery: 1-Year Follow-Up Study.

IMPORTANCE: The genital hiatus (GH) has been identified as a predictor of pelvic organ prolapse. An enlarged preoperative GH is a risk factor for recurrent prolapse after surgery. OBJECTIVE: The objective of this study was to determine the changes in preoperative and postoperative GH size compared with the intraoperative resting GH at 6 weeks and 12 months after native-tissue pelvic organ prolapse surgery. STUDY DESIGN: This was a descriptive analysis of a prospective cohort study of women undergoing native-tissue prolapse repair with apical suspension. Resting GH was obtained at the start and conclusion of surgery. Measurements were obtained preoperatively, and 6 weeks and 12 months postoperatively under Valsalva maneuver. Comparisons were made using paired t tests for the following time points: (1) preoperative measurements under Valsalva maneuver to resting presurgery measurements under anesthesia, and (2) resting postsurgery measurements under anesthesia to 6 weeks and 12 months postoperatively under Valsalva maneuver. RESULTS: Sixty-seven patients were included, with a median age of 66 years and median body mass index (calculated as weight in kilograms divided by height in meters squared) of 29.1. There was no significant difference in GH when measured preoperatively to resting presurgical measurements under anesthesia (P = 0.60). For all, the median GH was 3.0 cm at the conclusion of surgery and remained at 3.0 cm at 6 weeks and 12 months postoperatively. In patients who had a concurrent posterior colporrhaphy, the median resting postsurgery GH was 3.0 cm, then decreased to 2.5 cm at 6 weeks then 3.5 cm at 12 months under Valsalva. CONCLUSIONS: Preoperative GH size under Valsalva maneuver and resting under anesthesia were comparable. For all patients undergoing native-tissue pelvic organ prolapse repair, the genital hiatus size remains the same from the intraoperative final resting measurements to the 6-week and 12-month measurements under Valsalva maneuver.

Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC.

OBJECTIVES: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. MATERIALS AND METHODS: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis. CONCLUSIONS: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.

An update on drug-drug interactions in older adults living with human immunodeficiency virus (HIV).

INTRODUCTION: People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions - such as cardiovascular disease and cancer - and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes. AREA COVERED: Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug-drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors. EXPERT OPINION: Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug-drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications.

Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease.

Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

Effects of Obesity on Urogynecologic Prolapse Surgery Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the literature on outcomes of pelvic organ prolapse (POP) surgery in patients from various body mass index (BMI) categories to determine the association between obesity and surgical outcomes. DATA SOURCES: PubMed, EMBASE, and Cochrane databases were searched from inception to April 12, 2022; ClinicalTrials.gov was searched in September 2022 (PROSPERO 2022 CRD42022326255). Randomized and nonrandomized studies of urogynecologic POP surgery outcomes were accepted in which categories of BMI or obesity were compared. METHODS OF STUDY SELECTION: In total, 9,037 abstracts were screened; 759 abstracts were identified for full-text screening, and 31 articles were accepted for inclusion and data were extracted. TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant information, intervention, comparator, and outcomes, including subjective outcomes, objective outcomes, and complications. Outcomes were compared among obesity categories (eg, BMI 30-34.9, 35-40, higher than 40), and meta-analysis was performed among different surgical approaches. Individual studies reported varying results as to whether obesity affects surgical outcomes. By meta-analysis, obesity (BMI 30 or higher) is associated with an increased odds of objective prolapse recurrence after vaginal prolapse repair (odds ratio [OR] 1.38, 95% CI, 1.14-1.67) and after prolapse repair from any surgical approach (OR 1.31, 95% CI, 1.12-1.53) and with complications such as mesh exposure after both vaginal and laparoscopic POP repair (OR 2.10, 95% CI, 1.01-4.39). CONCLUSION: Obesity is associated with increased likelihood of prolapse recurrence and mesh complications after POP repair. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022326255.

Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.

PTEN knockout using retrogradely transported AAVs transiently restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and transiently restore locomotor functions in near-complete injury models. AAVrg's were injected to deliver cre recombinase and/or a red fluorescent protein (RFP) under the human Synapsin 1 promoter (hSyn1) into the spinal cords of C57BL/6 PTENFloxΔ/Δ mice to knockout PTEN (PTEN-KO) in a severe thoracic SCI crush model at both acute and chronic time points. PTEN-KO improved locomotor abilities in both acute and chronic SCI conditions over a 9-week period. Regardless of whether treatment was initiated at the time of injury (acute), or three months after SCI (chronic), mice with limited hindlimb joint movement gained hindlimb weight support after treatment. Interestingly, functional improvements were not sustained beyond 9 weeks coincident with a loss of RFP reporter-gene expression and a near-complete loss of treatment-associated functional recovery by 6 months post-treatment. Treatment effects were also specific to severely injured mice; animals with weight support at the time of treatment lost function over a 6-month period. Retrograde tracing with Fluorogold revealed viable neurons throughout the motor cortex despite a loss of RFP expression at 9 weeks post-PTEN-KO. However, few Fluorogold labeled neurons were detected within the motor cortex at 6 months post-treatment. BDA labeling from the motor cortex revealed a dense corticospinal tract (CST) bundle in all groups except chronically treated PTEN-KO mice, indicating a potential long-term toxic effect of PTEN-KO to neurons in the motor cortex which was corroborated by a loss of ß-tubulin III labeling above the lesion within spinal cords after PTEN-KO. PTEN-KO mice had significantly more ß-tubulin III labeled axons within the lesion when treatment was delivered acutely, but not chronically post-SCI. In conclusion, we have found that using AAVrg's to knockout PTEN is an effective manipulation capable of restoring motor functions in chronic SCI and can enhance axon growth of currently unidentified axon populations when delivered acutely after injury. However, the long-term consequences of PTEN-KO on neuronal health and viability should be further explored.

Changes in Pelvic Floor Symptoms After Procedural Interventions for Uterine Leiomyomas: A Systematic Review.

OBJECTIVE: To conduct a systematic review to evaluate the effect of procedural interventions for leiomyomas on pelvic floor symptoms. DATA SOURCES: PubMed, EMBASE, and ClinicalTrials.gov were searched from inception to January 12, 2023, searching for leiomyoma procedures and pelvic floor disorders and symptoms, restricted to primary study designs in humans. METHODS OF STUDY SELECTION: Double independent screening for studies of any study design in all languages that reported pelvic floor symptoms before and after surgical (hysterectomy, myomectomy, radiofrequency volumetric thermal ablation) or radiologic (uterine artery embolization, magnetic resonance-guided focused ultrasonography, high-intensity focused ultrasonography) procedures for management of uterine leiomyomas. Data were extracted, with risk-of-bias assessment and review by a second researcher. Random effects model meta-analyses were conducted, as feasible. TABULATION, INTEGRATION, AND RESULTS: Six randomized controlled trials, one nonrandomized comparative study, and 25 single-group studies met criteria. The overall quality of the studies was moderate. Only six studies, reporting various outcomes, directly compared two procedures for leiomyomas. Across studies, leiomyoma procedures were associated with decreased symptom distress per the UDI-6 (Urinary Distress Inventory, Short Form) (summary mean change -18.7, 95% CI -25.9 to -11.5; six studies) and improved quality of life per the IIQ-7 (Incontinence Impact Questionnaire, Short Form) (summary mean change -10.7, 95% CI -15.8 to -5.6; six studies). There was a wide range of resolution of urinary symptoms after procedural interventions (7.6-100%), and this varied over time. Urinary symptoms improved in 19.0-87.5% of patients, and the definitions for improvement varied between studies. Bowel symptoms were inconsistently reported in the literature. CONCLUSION: Urinary symptoms improved after procedural interventions for uterine leiomyomas, although there is high heterogeneity among studies and few data on long-term outcomes or comparing different procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021272678.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. OBJECTIVE: We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. SETTING: Three specialized treatment centers in Sweden. METHODS: Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. RESULTS: At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). CONCLUSIONS: Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

PTEN knockout using retrogradely transported AAVs restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and restore locomotor functions in near-complete injury models. AAVrg's were injected to deliver cre recombinase and/or a red fluorescent protein (RFP) under the human Synapsin 1 promoter (hSyn1) into the spinal cords of C57BL/6 PTEN FloxΔ / Δ mice to knockout PTEN (PTEN-KO) in a severe thoracic SCI crush model at both acute and chronic time points. PTEN-KO improved locomotor abilities in both acute and chronic SCI conditions over a 9-week period. Regardless of whether treatment was initiated at the time of injury (acute), or three months after SCI (chronic), mice with limited hindlimb joint movement gained hindlimb weight support after treatment. Interestingly, functional improvements were not sustained beyond 9 weeks coincident with a loss of RFP reporter-gene expression and a near-complete loss of treatment-associated functional recovery by 6 months post-treatment. Treatment effects were also specific to severely injured mice; animals with weight support at the time of treatment lost function over a 6-month period. Retrograde tracing with Fluorogold revealed viable neurons throughout the motor cortex despite a loss of RFP expression at 9 weeks post-PTEN-KO. However, few Fluorogold labeled neurons were detected within the motor cortex at 6 months post-treatment. BDA labeling from the motor cortex revealed a dense corticospinal tract (CST) bundle in all groups except chronically treated PTEN-KO mice indicating a potential long-term toxic effect of PTEN-KO to neurons in the motor cortex. PTEN-KO mice had significantly more ß - tubulin III labeled axons within the lesion when treatment was delivered acutely, but not chronically post-SCI. In conclusion, we have found that using AAVrg's to knockout PTEN is an effective manipulation capable of restoring motor functions in chronic SCI and can enhance axon growth of currently unidentified axon populations when delivered acutely after injury. However, the long-term consequences of PTEN-KO may exert neurotoxic effects.

Changes in sexual function over 12 months after native-tissue vaginal pelvic organ prolapse surgery with and without hysterectomy.

Background: There is a need to determine how preoperative sexual activity, uterine preservation, and hysterectomy affect sexual function after pelvic organ prolapse surgery. Aim: (1) To determine changes in sexual function in women, stratified by preoperative sexual activity status, after native-tissue pelvic organ prolapse surgery. (2) To examine the impact of hysterectomy and uterine preservation on sexual function. (3) To determine predictors for postoperative dyspareunia. Methods: This was a planned secondary analysis of a prospective cohort study. Sexual function was evaluated preoperatively and 6 and 12 months postoperatively. Sexual function was compared between those who had a hysterectomy and those who had uterine-preserving prolapse surgery. A logistic regression analysis was performed to assess predictors for dyspareunia. Outcomes: Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire. Results: At 12 months, 59 patients underwent surgery and were followed up (hysterectomy [n = 28, 47.5%] vs no hysterectomy [n = 31, 52.5%]; sexually active [n = 26, 44.1%] vs non-sexually active [n = 33, 55.9%]). Of those who did not undergo a hysterectomy, 17 (54.8%) had a uterine-preserving procedure. At 12 months, sexually active patients had significant improvement in sexual function (mean ± SD, 0.37 ± 0.43; P = .005), while non-sexually active patients reported significant improvement in satisfaction of sex life (P = .04) and not feeling sexually inferior (P = .003) or angry (P = .03) because of prolapse. No variables were associated with dyspareunia on bivariate analysis. Clinical Implications: It did not appear that either uterine preservation or hysterectomy had any impact on sexual function. There was a 10% increase in people who were sexually active after surgery. Strengths and Limitations: The major strength of our study is the use of a condition-specific validated questionnaire intended for sexually active and non-sexually active women. We interpreted our results utilizing a validated minimal clinically important difference score to provide interpretation of our results with statistical and clinical significance. The limitation of our study is that it was a secondary analysis that was not powered for these specific outcomes. Conclusion: At 12 months, for patients who were sexually active preoperatively, there was a clinically meaningful improvement in sexual function after native-tissue pelvic organ prolapse surgery. Non-sexually active women reported improvement in satisfaction of sex life. There was no difference in the sexual function of patients undergoing uterine preservation or posthysterectomy colpopexy when compared with those with concurrent hysterectomy, though this sample size was small.

Intention matters: Success rate of bilateral salpingo-oophorectomy at the time of vaginal hysterectomy for pelvic organ prolapse.

OBJECTIVE: The objective of this study was to determine the incidence of successful bilateral salpingo-oophorectomy at the time of vaginal hysterectomy for pelvic organ prolapse and to evaluate associated factors and success rate over time. STUDY DESIGN: This was a retrospective chart review of all women who underwent vaginal hysterectomy for pelvic organ prolapse who were consented for bilateral salpingo-oophorectomy "if possible" and "including extraordinary measures" between 2014 and 2019 at a tertiary medical center. Baseline demographic data along with prolapse stage, operative findings, operative time, and complications were recorded. Univariate analysis using the Pearson's chi-square test, the student's t-test or Mann Whitney U test when appropriate and multivariable logistic regression was performed to determine predictors of successful vaginal bilateral salpingo-oophorectomy. RESULTS: A total of 453 eligible patients were included. 420 patients (92.7 %) were consented for bilateral salpingo-oophorectomy "if possible" and 33 patients (7.3 %) were consented for "including extraordinary measures". The success rate of vaginal bilateral salpingo-oophorectomy in all patients was 57.9 % (n = 262). Of the patients consented for extraordinary measures, the success rate was 93.9 % (n = 31), compared to a success rate of 55 % (n = 231) in the "if possible" group. A concurrent posterior repair was found to have higher odds of successful bilateral salpingo-oophorectomy (adjOR 1.75 [95 % CI = 1.17-2.61]). Successful bilateral salpingo-oophorectomy extended operative time by 14 min (154 min vs 140 min, p < 0.001). Compared to patients in the unsuccessful group, the successful group had a higher proportion of the following indications: a family history of ovarian cancer, personal breast cancer history or patient request for definitive removal. CONCLUSION: When the pre-operative intention to perform bilateral salpingo-oophorectomy at the time of vaginal hysterectomy for pelvic organ prolapse is high, the success rate is nearly 40% higher when compared to an opportunistic procedure. This suggests that success is closely linked to the surgeon's determination to complete this procedure vaginally.

Antioxidant enzymes that target hydrogen peroxide are conserved across the animal kingdom, from sponges to mammals.

Oxygen is the sustenance of aerobic life and yet is highly toxic. In early life, antioxidants functioned solely to defend against toxic effects of reactive oxygen species (ROS). Later, as aerobic metabolisms evolved, ROS became essential for signalling. Thus, antioxidants are multifunctional and must detoxify, but also permit ROS signalling for vital cellular processes. Here we conduct metazoan-wide genomic assessments of three enzymatic antioxidant families that target the predominant ROS signaller, hydrogen peroxide: namely, monofunctional catalases (CAT), peroxiredoxins (PRX), and glutathione peroxidases (GPX). We reveal that the two most evolutionary ancient families, CAT and PRX, exhibit metazoan-wide conservation. In the basal animal lineage, sponges (phylum Porifera), we find all three antioxidant families, but with GPX least abundant. Poriferan CATs are distinct from bilaterian CATs, but the evolutionary divergence is small. Amongst PRXs, subfamily PRX6 is the most conserved, whilst subfamily AhpC-PRX1 is the largest; PRX4 is the only core member conserved from sponges to mammals and may represent the ancestral animal AhpC-PRX1. Conversely, for GPX, the most recent family to arise, only the cysteine-dependent subfamily GPX7 is conserved across metazoans, and common across Porifera. Our analyses illustrate that the fundamental functions of antioxidants have resulted in gene conservation throughout the animal kingdom.

Revision sacrocolpopexy: tips and tricks for optimal outcomes.

INTRODUCTION AND HYPOTHESIS: The aim of this video is to highlight important considerations and techniques for revision sacrocolpopexy in women with symptomatic recurrence of pelvic organ prolapse after sacrocolpopexy. METHODS: In this video, we show five patients who presented with recurrent symptomatic pelvic organ prolapse after prior sacrocolpopexy. We demonstrate techniques for robotic-assisted laparoscopic sacrocolpopexy revision including surgical dissection, revision of existing mesh, and/or addition of new mesh. CONCLUSIONS: Overall, revision sacrocolpopexy requires an individualized approach. These surgeries are often challenging because of adhesions and altered anatomy from the prior sacrocolpopexy. The reviewed considerations and techniques can be useful for ensuring a safe and effective outcome.

Who Places High Value on the Uterus? A Cross-sectional Survey Study Evaluating Predictors for Uterine Preservation.

STUDY OBJECTIVE: To determine predictors for placing high value on the uterus in patients who no longer desire fertility. The secondary objective was to identify reasons for placing high value on the uterus. DESIGN: Cross-sectional survey study. SETTING: Three hospitals within a large healthcare system in the United States. PATIENTS: New patients ≥45 years old seeking care for benign gynecologic conditions, including abnormal uterine bleeding, uterine myomas, pelvic organ prolapse, endometriosis, or pelvic pain. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the summative score of the validated Value of Uterus (VALUS) instrument for measuring value placed on the uterus and the validated visual analog scale with the question "how important is it to you to keep your uterus when you have a gynecologic condition?" A total of 163 surveys were returned for analysis (79.2%). Using the VALUS cutoff, 64 patients (45.7%) were considered to have low value for their uterus (VALUS score <14), whereas 76 patients (54.3%) were considered to have high value for their uterus (VALUS score ≥14). The adjusted odds of placing high value for the uterus was 5.06 times higher among those who wanted to be sexually active in the future than those who do not desire to be sexually active (95% confidence interval, 1.55-16.52, p = .01). Patients who are sexually active have 3.94 higher adjusted odds of placing high value on the uterus than those who are not sexually active and do not desire to be (95% confidence interval, 1.36-11.43; p = .01). Race, religion, and personal history of cancer were not statistically significant. CONCLUSION: Patients who highly value the uterus were highly motivated by the desire to be sexually active. Nonwhite race, religion, and personal history of cancer were not predictors for placing high value on uterine preservation.

The Concerns and Experiences of Patients With Lumbar Spinal Stenosis Regarding Prehabilitation and Recovery After Spine Surgery: A Qualitative Study.

Objectives: To improve our understanding of patients' perspectives regarding: (1) the decision-making and prehabilitation before lumbar spinal stenosis (LSS) surgery and (2) their postoperative experiences. Design: Qualitative research with semi-structured interviews. Setting: General community. Participants: Individuals who received (N=10) and who did not receive (N=15) prehabilitation before LSS surgery were recruited at the 6-month postoperative follow-up (8 females; average age: 67.7±6.7 years) by purposive sampling. Additionally, 1 participant invited her daughter to accompany her in an interview. Interventions: Not applicable. Main Outcome Measures: Concerns and experiences of patients with LSS regarding prehabilitation and recovery after spine surgery. Results: Thematic analysis was conducted to identify 4 themes inductively: (1) sources of information about LSS surgery; (2) factors affecting the surgical decision-making; (3) attitudes toward prehabilitation; and (4) postoperative recovery. All participants desired to have more preoperative education to inform their surgical decision-making. There were mixed opinions regarding the perceived benefits of prehabilitation because some individuals hesitated to participate in prehabilitation because of their symptoms, or the cost or time of traveling. Many participants expected some or even complete relief of LSS-related symptoms after surgery. However, not all participants experienced the expected postoperative improvements. Some participants only experienced temporary symptomatic relief, while others experienced new postoperative symptoms. Patients generally found that postoperative exercises taught by physiotherapists were useful although their compliance decreased over time. Conclusions: Our study highlights the need for better preoperative LSS education. Because face-to-face prehabilitation or postoperative rehabilitation may not be feasible for all patients, future studies should explore whether online-based prehabilitation or postoperative rehabilitation may benefit certain patient subgroups.

Determining the Ideal Intraoperative Resting Genital Hiatus Size-Balancing Surgical and Functional Outcomes.

IMPORTANCE: The intraoperative resting genital hiatus (GH) size can be surgically modified but its relationship to prolapse recurrence is unclear. OBJECTIVES: The objective of this study was to identify the optimal intraoperative resting GH size as it relates to prolapse recurrence and functional outcomes at 1 year. STUDY DESIGN: This prospective cohort study was conducted at 2 hospitals from 2019 to 2021. Intraoperative measurements of the resting GH, perineal body, and total vaginal length were collected. The composite primary outcome consisted of anatomic recurrence, subjective recurrence, and/or conservative or surgical retreatment at 1 year. Comparisons of anatomic, functional, and sexual outcomes were compared between patients stratified by the optimal intraoperative GH size identified by receiver operating characteristic curve analysis. RESULTS: Sixty-eight patients (median age of 63 years) underwent surgery, with 59 (86.8%) presenting for follow-up at 1 year. Based on the 13 patients (22%) with composite recurrence, receiver operating characteristic curve analysis demonstrated an intraoperative resting GH size of 3 cm, had 76.9% sensitivity (confidence interval [CI], 54-99.8%), and 34.8% specificity (CI, 21.0-48.5%) for composite recurrence at 1 year (area under curve = 0.61). Nineteen patients had an intraoperative GH less than 3 cm (32.2%) and 40 had a GH of 3 cm or greater (67.8%). The intraoperative resting GH size was significantly larger in patients with prolapse beyond the hymen at 1 year (4 cm [3.0, 4.0]) compared with those with prolapse at or proximal to the hymen (3.0 cm [2.5, 3.5], P = 0.009). CONCLUSIONS: Intraoperative GH size may not reliably predict composite prolapse recurrence at 1 year, although there was an association between intraoperative resting GH size with prolapse beyond the hymen.