A Case of a Prolapsing Cervical Fibroid Managed with Robot-Assisted Total Laparoscopic Hysterectomy.

The development of cervical fibroids is rare, but they are often symptomatic and can be associated with complications such as bleeding, pain, constipation, and prolapse. Necrosed, prolapsing fibroids can lead to massive acute hemorrhage. Treatment is, therefore, typically necessary, but surgical management is frequently technically difficult given distorted anatomy. We present several images of a prolapsing cervical fibroid treated by hysterectomy in a 53-year-old patient.

Racial Disparities in Hysterectomy Route for Benign Disease: Examining Trends and Perioperative Complications from 2007 to 2018 Using the NSQIP Database.

STUDY OBJECTIVE: To examine national trends among race and ethnicity and route of benign hysterectomy from 2007 to 2018. DESIGN: This is a retrospective analysis of the prospective National Surgical Quality Improvement Program cohort program. SETTING: This study included data from the National Surgical Quality Improvement Program database including data from the 2014 to 2018 targeted hysterectomy files. PATIENTS: Adult patients undergoing hysterectomy. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Current Procedural Terminology codes identified women undergoing benign hysterectomy and perioperative data including race and ethnicity were obtained. To determine relative trends in hysterectomy among race and ethnicity cohorts (White, Black, Hispanic), we calculated the proportion of each procedure performed annually within each race and ethnicity group and compared it across groups. From 2007 to 2018, 269 794 hysterectomies were collected (190 154 White, 45 756 Black, and 33 884 Hispanic). From 2007 to 2018, rates of laparoscopic hysterectomy increased in all cohorts (30.2%-71.6% for White, 23.9%-58.5% for Black, 19.9%-64.0% for Hispanic; ptrend <0.01 for all). For each year from 2007 to 2018, the proportion of women undergoing open abdominal hysterectomy remained twice as high in Black Women compared with White women (33.1%-14.4%, p <.01). Data from the 2014 to 2018 targeted files showed Black and Hispanic women undergoing benign hysterectomy were generally younger, had larger uteri, were more likely to be current smokers, have diabetes and/or hypertension, have higher body mass index, and have undergone previous pelvic surgery (p ≤.01 for all). CONCLUSION: Compared with White women, Black and Hispanic women are less likely to undergo benign hysterectomy via a minimally invasive approach. Although larger uteri and comorbid conditions may attribute to higher rates of open abdominal hysterectomy, the higher prevalence of abdominal hysterectomy among younger Black and Hispanic women highlights potential racial disparities in women's health and access to care.

Predictors of Admission After the Implementation of an Enhanced Recovery After Surgery Pathway for Minimally Invasive Gynecologic Surgery.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways in gynecologic surgery have been shown to decrease length of stay with no impact on readmission, but no study has assessed predictors of admission in this population. The purpose of this study was to identify predictors of admission after laparoscopic hysterectomy (LH) and robotic-assisted hysterectomy (RAH) performed under an ERAS pathway. METHODS: This is a prospective observational study of women undergoing LH/RAH for benign indications within an ERAS pathway. Data collected included same-day discharge, reason for admission, incidences of urgent clinic and emergency room (ER) visits, readmissions, reoperations, and 9 postulated predictors of admission listed below. Patient demographics, markers of baseline health, and clinical outcomes were compared between groups (ERAS patients discharged on the day of surgery versus admitted) using Fisher exact and Student t tests. Multivariable logistic regression was used to assess the potential risk factors for being admitted, adjusting for age, race, body mass index, American Society of Anesthesiologists (ASA) physical status score, preoperative diagnosis indicative of hysterectomy, preoperative chronic pain, completion of a preprocedure pain-coping skills counseling session, procedure time, and compliance to the ERAS pathway. RESULTS: There were 165 patients undergoing LH/RAH within an ERAS pathway; 93 (56%) were discharged on the day of surgery and 72 were admitted. There were no significant differences in ER visits, readmissions, and reoperations between groups (ER visits: discharged 13% versus admitted 13%, P = .99; 90-day readmission: discharged 4% versus admitted 7%, P = .51; and 90-day reoperation: discharged 4% versus admitted 3%, P = .70). The most common reasons for admission were postoperative urinary retention (n = 21, 30%), inadequate pain control (n = 21, 30%), postoperative nausea and vomiting (n = 7, 10%), and planned admissions (n = 7, 10%). Increased ASA physical status, being African American, and increased length of procedure were significantly associated with an increased risk of admission (ASA physical status III versus ASA physical status I or II: odds ratio [OR], 3.12; 95% confidence interval [CI], 1.36-7.16; P = .007; African American: OR, 2.47; 95% CI, 1.02-5.96; P = .04; and length of procedure, assessed in 30-minute increments: OR, 1.23; 95% CI, 1.02-1.50; P = .04). CONCLUSIONS: We were able to define predictors of admission for patients having LH/RAH managed with an ERAS pathway. Increased ASA physical status, being African American, and increased length of procedure were significantly associated with admission after LH/RAH performed under an ERAS pathway. In addition, the incidences of urgent clinic and ER visits, readmissions, and reoperations within 90 days of surgery were similar for patients who were discharged on the day of surgery compared to those admitted.

Use of Historic Surgical Times to Predict Duration of Hysterectomy: Stratifying by Uterine Weight.

STUDY OBJECTIVE: To describe the accuracy of historic averages for estimating operating room (OR) time for hysterectomy among women with small and large uteri. DESIGN: A retrospective cohort study. SETTING: Data from women who underwent abdominal, vaginal, or laparoscopic hysterectomy between 2015 and 2017 at the University of North Carolina Hospitals were analyzed. Historic and actual OR times were compared using linear regression. Patient characteristics were also evaluated to determine whether they were associated with the accuracy of predicted OR times. PATIENTS: Nine hundred eighty-five adult women (≥18 years old) who underwent surgery for benign indications or for suspected but not biopsy-confirmed malignancy were included. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Historic averages overestimated OR time by a median of 14 minutes (interquartile range [IQR] = -29 to 49 minutes). The OR time in women with small uteri (<250 g) was significantly more likely to be overestimated than women with large uteri (≥250 g) (median time = 21 minutes [IQR = -16 to 52 minutes] and 3 minutes [IQR = -38 to 44 minutes], respectively; p <. 001). In total laparoscopic hysterectomy and laparoscopy-assisted vaginal hysterectomy, women with uteri ≥250 g took significantly longer than hysterectomy for women with uteri <250 g (36 minutes longer [95% confidence interval, 24-50] and 95 minutes longer [95% confidence interval, 12-179], respectively; p < .001 and p = .03). CONCLUSION: Using historic averages overestimates OR time, and it is more pronounced in women with small uteri. However, there is a relatively large range of OR times, even among women with the same size uteri. This study highlights the importance of preoperative planning, and in cases in which endometriosis is expected, manually adding time to estimates is recommended.

Opioid Adjuncts: Optimizing Opioid Therapy With Nonopioid Medications.

In this article, we describe a variety of medications that physicians managing outpatient chronic pain should familiarize themselves with to better aid their approach to multimodal pain therapy. Physicians should always consider the use of an adjuvant or coanalgesic drug as first-line treatments. Although many of these medications are not primarily analgesics, in clinical practice they have independent analgesic effects or synergistic analgesic properties when used with opioids. The use of adjunct analgesics reduces opioid-related adverse effects and optimizes pain management. Although there may be some medication overlap with this section and the ERAS section, the purpose of this article is to understand prolonged use in the outpatient setting to reduce opioid use or limit opioid dose with adjuvant therapy.

Uterine weight and complications after abdominal, laparoscopic, and vaginal hysterectomy.

BACKGROUND: Although uterine size has been a previously cited barrier to minimally invasive hysterectomy, experienced gynecologic surgeons have been able to demonstrate that laparoscopic and vaginal hysterectomy is feasible with increasingly large uteri. By demonstrating that minimally invasive hysterectomy continues to have superior outcomes even with increased uterine weights, opportunity exists to meaningfully decrease morbidity, mortality, and cost associated with abdominal hysterectomy. OBJECTIVE: We sought to determine if there is an association between uterine weight and posthysterectomy complications and if differences in that association exist across vaginal, laparoscopic, and abdominal approaches. STUDY DESIGN: We conducted a cohort study of prospectively collected quality improvement data from the American College of Surgeons National Surgical Quality Improvement Program database, composed of patient information and 30-day postoperative outcomes from >500 hospitals across the United States and targeted data files, which includes additional data on procedure-specific risk factors and outcomes in >100 of those participating hospitals. We analyzed patients undergoing hysterectomy for benign conditions from 2014 through 2015, identified by Current Procedural Terminology code. We excluded patients who had cancer, surgery by a nongynecology specialty, or missing uterine weight. Patients were compared with respect to 30-day postoperative complications and uterine weight, stratified by surgical approach. Bivariable tests and multivariable logistic regression were used for analysis. RESULTS: In all, 27,167 patients were analyzed. After adjusting for potential confounders, including medical and surgical variables, women with 500-g uteri were >30% more likely to have complications compared to women with uteri ≤100 g (adjusted odds ratio, 1.34; 95% confidence interval, 1.17-1.54; P < .0001), women with 750-g uteri were nearly 60% as likely (adjusted odds ratio, 1.58; 95% confidence interval, 1.37-1.82; P < .0001), and women with uteri ≥1000 g were >80% more likely (adjusted odds ratio, 1.85; 95% confidence interval, 1.55-2.21; P < .0001). The incidence of 30-day postsurgical complications was nearly double in the abdominal hysterectomy group (15%) compared to the laparoscopic group (8%). Additionally, for each stratum of uterine weight, abdominal hysterectomy had significantly higher odds of any complication compared to laparoscopic hysterectomy, even after adjusting for potential demographic, medical, and surgical confounders. For uteri <250 g, abdominal hysterectomy had twice the odds of any complication, compared to laparoscopic hysterectomy (adjusted odds ratio, 2.05; 95% confidence interval, 1.80-2.33), and among women with uteri between 250-500 g, abdominal hysterectomy was associated with an almost 80% increase in odds of any complication (adjusted odds ratio, 1.76; 95% confidence interval, 1.41-2.19). Even among women with uteri >500 g, abdominal hysterectomy was still associated with a >30% increased odds of any complication, compared to laparoscopic hysterectomy (adjusted odds ratio, 1.35; 95% confidence interval, 1.07-1.71). CONCLUSION: We found that while uterine weight was an independent risk factor for posthysterectomy complications, abdominal hysterectomy had higher odds of any complication, compared to laparoscopic hysterectomy, even for markedly enlarged uteri. Our study suggests that uterine weight alone is not an appropriate indication for abdominal hysterectomy. We also identified that it is safe to perform larger hysterectomies laparoscopically. Patients may benefit from referral to experienced surgeons who are able to offer laparoscopic hysterectomy even for markedly enlarged uteri.

Optimizing research in symptomatic uterine fibroids with development of a computable phenotype for use with electronic health records.

BACKGROUND: Women with symptomatic uterine fibroids can report a myriad of symptoms, including pain, bleeding, infertility, and psychosocial sequelae. Optimizing fibroid research requires the ability to enroll populations of women with image-confirmed symptomatic uterine fibroids. OBJECTIVE: Our objective was to develop an electronic health record-based algorithm to identify women with symptomatic uterine fibroids for a comparative effectiveness study of medical or surgical treatments on quality-of-life measures. Using an iterative process and text-mining techniques, an effective computable phenotype algorithm, composed of demographics, and clinical and laboratory characteristics, was developed with reasonable performance. Such algorithms provide a feasible, efficient way to identify populations of women with symptomatic uterine fibroids for the conduct of large traditional or pragmatic trials and observational comparative effectiveness studies. Symptomatic uterine fibroids, due to menorrhagia, pelvic pain, bulk symptoms, or infertility, are a source of substantial morbidity for reproductive-age women. Comparing Treatment Options for Uterine Fibroids is a multisite registry study to compare the effectiveness of hormonal or surgical fibroid treatments on women's perceptions of their quality of life. Electronic health record-based algorithms are able to identify large numbers of women with fibroids, but additional work is needed to develop electronic health record algorithms that can identify women with symptomatic fibroids to optimize fibroid research. We sought to develop an efficient electronic health record-based algorithm that can identify women with symptomatic uterine fibroids in a large health care system for recruitment into large-scale observational and interventional research in fibroid management. STUDY DESIGN: We developed and assessed the accuracy of 3 algorithms to identify patients with symptomatic fibroids using an iterative approach. The data source was the Carolina Data Warehouse for Health, a repository for the health system's electronic health record data. In addition to International Classification of Diseases, Ninth Revision diagnosis and procedure codes and clinical characteristics, text data-mining software was used to derive information from imaging reports to confirm the presence of uterine fibroids. Results of each algorithm were compared with expert manual review to calculate the positive predictive values for each algorithm. RESULTS: Algorithm 1 was composed of the following criteria: (1) age 18-54 years; (2) either ≥1 International Classification of Diseases, Ninth Revision diagnosis codes for uterine fibroids or mention of fibroids using text-mined key words in imaging records or documents; and (3) no International Classification of Diseases, Ninth Revision or Current Procedural Terminology codes for hysterectomy and no reported history of hysterectomy. The positive predictive value was 47% (95% confidence interval 39-56%). Algorithm 2 required ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids and positive text-mined key words and had a positive predictive value of 65% (95% confidence interval 50-79%). In algorithm 3, further refinements included ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids on separate outpatient visit dates, the exclusion of women who had a positive pregnancy test within 3 months of their fibroid-related visit, and exclusion of incidentally detected fibroids during prenatal or emergency department visits. Algorithm 3 achieved a positive predictive value of 76% (95% confidence interval 71-81%). CONCLUSION: An electronic health record-based algorithm is capable of identifying cases of symptomatic uterine fibroids with moderate positive predictive value and may be an efficient approach for large-scale study recruitment.

Cost-effectiveness of treatments for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects up to one third of women in the United States, resulting in a reduced quality of life and significant cost to the health care system. Multiple treatment options exist, offering different potential for symptom control at highly variable initial costs, but the relative value of these treatment options is unknown. OBJECTIVE: The objective of the study was to evaluate the relative cost-effectiveness of 4 treatment options for heavy menstrual bleeding: hysterectomy, resectoscopic endometrial ablation, nonresectoscopic endometrial ablation, and the levonorgestrel-releasing intrauterine system. STUDY DESIGN: We formulated a decision tree evaluating private payer costs and quality-adjusted life years over a 5 year time horizon for premenopausal women with heavy menstrual bleeding and no suspected malignancy. For each treatment option, we used probabilities derived from literature review to estimate frequencies of minor complications, major complications, and treatment failure resulting in the need for additional treatments. Treatments were compared in terms of total average costs, quality-adjusted life years, and incremental cost-effectiveness ratios. Probabilistic sensitivity analysis was conducted to understand the range of possible outcomes if model inputs were varied. RESULTS: The levonorgestrel-releasing intrauterine system had superior quality-of-life outcomes to hysterectomy with lower costs. In a probabilistic sensitivity analysis, levonorgestrel-releasing intrauterine system was cost-effective compared with hysterectomy in the majority of scenarios (90%). Both resectoscopic and nonresectoscopic endometrial ablation were associated with reduced costs compared with hysterectomy but resulted in a lower average quality of life. According to standard willingness-to-pay thresholds, resectoscopic endometrial ablation was considered cost effective compared with hysterectomy in 44% of scenarios, and nonresectoscopic endometrial ablation was considered cost effective compared with hysterectomy in 53% of scenarios. CONCLUSION: Comparing all trade-offs associated with 4 possible treatments of heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system was superior to both hysterectomy and endometrial ablation in terms of cost and quality of life. Hysterectomy is associated with a superior quality of life and fewer complications than either type of ablation but at a higher cost. For women who are unwilling or unable to choose the levonorgestrel-releasing intrauterine system as a first-course treatment for heavy menstrual bleeding, consideration of cost, procedure-specific complications, and patient preferences can guide the decision between hysterectomy and ablation.

The role of simulation and warm-up in minimally invasive gynecologic surgery.

PURPOSE OF REVIEW: The purpose of the review is to update the reader on the current literature and recent studies evaluating the role of simulation and warm-up as part of surgical education and training, and maintenance of surgical skills. RECENT FINDINGS: Laparoscopic and hysteroscopic simulation may improve psychomotor skills, particularly for early-stage learners. However, data are mixed as to whether simulation education is directly transferable to surgical skill. Data are insufficient to determine if simulation can improve clinical outcomes. Similarly, performance of surgical warm-up exercises can improve performance of novice and expert surgeons in a simulated environment, but the extent to which this is transferable to intraoperative performance is unknown. Surgical coaching, however, can facilitate improvements in performance that are directly reflected in operative outcomes. SUMMARY: Simulation-based curricula may be a useful adjunct to residency training, whereas warm-up and surgical coaching may allow for maintenance of skill throughout a surgeon's career. These experiences may represent a strategy for maintaining quality and value in a lower volume surgical setting.

Risk factors for trachelectomy following supracervical hysterectomy.

INTRODUCTION: We identified risk factors for trachelectomy after supracervical hysterectomy (SCH) due to persistence of symptoms. MATERIAL AND METHODS: A retrospective case-control study in a university-affiliated hospital. Seventeen women who underwent a trachelectomy following SCH for nonmalignant indications between June 2002 and October 2014 were compared with 68 randomly selected women (controls) who underwent a SCH within the same time period. Demographics and clinical characteristics were compared between the study and control groups. Univariate analysis identified potential risk factors for trachelectomy following SCH. Univariate logistic regression models predicted which patients would have a trachelectomy following SCH. RESULTS: The occurrence of trachelectomy following SCH during the study period was 0.9% (17/1892). The study group was younger than the control group (mean age 38 ± 6 years vs. 44 ± 5 years; p < 0.001). Patients who had a history of endometriosis [odds ratio (OR) 6.23, 95% CI 1.11-40.5, p = 0.038] had increased risk for trachelectomy. Pathology diagnosed endometriosis only among women in the study group. Preoperative diagnosis of abnormal uterine bleeding (OR 0.22, 95% CI 0.06-0.075, p = 0.016), anemia (OR 0.12, 95% CI 0.01-0.53; p = 0.003), and fibroid uterus (OR 0.24, 95% CI 0.07-0.82, p = 0.024) reduced the risk for future trachelectomy. CONCLUSION: Young age and endometriosis are significant risk factors for trachelectomy following SCH.

Considerations for minimally invasive gynecologic surgery in obese patients.

PURPOSE OF REVIEW: The purpose is to review the key anatomical and physiological changes in obese patients and their effects on preoperative, intraoperative, and postoperative care and to highlight the best practices to safely extend minimally invasive approaches to obese patients and provide optimal surgical outcomes in this high-risk population. RECENT FINDINGS: Minimally invasive surgery is safe, feasible, and cost-effective for obese patients. Obesity is associated with anatomical and physiological changes in almost all organ systems, which necessitates a multimodal approach and an experienced, multidisciplinary team. Preoperative counseling, evaluation, and optimization of medical comorbidities are critical. The optimal minimally invasive approach is primarily determined by the patient's anatomy and pathology. Specific intraoperative techniques and modifications exist to maximize surgical exposure and panniculus management. Postoperatively, comprehensive medical management can help prevent common complications in obese patients, including hypoxemia, venous thromboembolism, acute kidney injury, hyperglycemia, and prolonged hospitalization. SUMMARY: Given significantly improved patient outcomes, minimally invasive approaches to gynecological surgery should be considered for all obese patients with particular attention given to specific perioperative considerations and appropriate referral to an experienced minimally invasive surgeon.

Peritoneal Washings After Power Morcellation in Laparoscopic Myomectomy: A Pilot Study.

STUDY OBJECTIVE: To evaluate if peritoneal washings of the abdominopelvic cavity during laparoscopic myomectomy can detect leiomyoma cells after power morcellation. DESIGN: Prospective cohort pilot study. SETTING: University of North Carolina Hospitals, an academic, tertiary referral center (Canadian Task Force classification II-2). PATIENTS: Patients undergoing laparoscopic or robotic myomectomy for suspected benign leiomyoma by members of the Minimally Invasive Gynecologic Surgery division between September 2014 and January 2015. INTERVENTION: Washings of the peritoneal cavity were collected at 3 times during surgery: the beginning of the procedure once the peritoneal cavity was accessed laparoscopically, after the myoma was excised and myometrial incision closed, and after uncontained power morcellation. MEASUREMENTS AND MAIN RESULTS: Twenty patients were included in the analysis. The median morcellation time was 16 minutes (range, 2-36). The median specimen weight was 283.5 g (range, 13-935). Cytologic evaluation (ThinPrep with Papanicolaou staining) did not detect any smooth muscle cells. Cell block histology, however, detected spindle cells in 6 postmorcellation samples. Three of these 6 cases also had spindle cells detected on the postmyomectomy closure samples. When performed on the postmorcellation samples, desmin and smooth muscle actin immunostaining were positive, confirming the presence of smooth muscle cells. CONCLUSION: Cell block histology, but not cytology, can detect leiomyoma cells in peritoneal washings after power morcellation. With myomectomy, there is some tissue disruption that seems to cause cell spread even in the absence of morcellation. Further protocol testing might allow peritoneal washings to be used in assessing containment techniques and testing comparative safety of different morcellation methods.

Robotic-assisted laparoscopic removal of cesarean scar ectopic and hysterotomy revision.

A 38-year-old gravida 6 para 2042 woman presented in consultation regarding management of a uterine defect, or "niche," following resolution of a cesarean scar ectopic pregnancy. She had 3 prior losses, followed by in vitro fertilization that resulted in 2 healthy births, both delivered by cesarean. A third in vitro embryo transfer resulted in the cesarean scar ectopic. After consideration of treatment options, she underwent multiple-dose parenteral methotrexate with eventual termination of the ectopic. Magnetic resonance imaging demonstrated a uterine defect, suspected to contain residual pregnancy tissue. Questions considered in her consultation included whether the defect should be repaired and, if so, from a hysteroscopic or laparoscopic approach, as well as her risk of intrauterine scarring, when, or if, it would be safe to pursue another pregnancy, and her subsequent risk of uterine rupture. Literature review regarding cesarean niche was helpful, but did not seem to completely inform this particular clinical scenario. She elected to proceed with robotic-assisted laparoscopic repair. The vesicovaginal space was opened to expose the defect. Dilute vasopressin was injected circumferentially around the defect to help minimize the use of electrosurgery in opening the hysterotomy. Scar overlying the defect was resected and pregnancy tissue removed. The hysterotomy was closed with delayed-absorbable barbed suture, extrapolating technique from laparoscopic myomectomy. The first layer was imbricated with a second, similar to a 2-layer closure in cesarean delivery. Follow-up magnetic resonance imaging revealed resolution of the defect. After several failed attempts at repeat in vitro fertilization, spontaneous pregnancy was achieved 18 months postoperatively. The pregnancy was uncomplicated and she underwent scheduled cesarean delivery of a healthy neonate at 37 weeks' gestation. The lower uterine segment was thick and developed, with no evidence of a dehiscence.

Is cervix removal associated with patient-centered outcomes of pain, dyspareunia, well-being and satisfaction after laparoscopic hysterectomy?

PURPOSE: To determine the effect of cervix removal at hysterectomy on patient-centered outcomes including post-operative pain, dyspareunia, well-being, and overall satisfaction during the 3-month post-operative period. METHODS: This is a prospective cohort study of 228 women who underwent elective abdominal, laparoscopic and robotic hysterectomy without concomitant urogynecological or cancer-related procedures, at the Henry Ford Hospital (Detroit, MI). Participants completed a baseline survey evaluating quality of life measures including pain, well-being, sexual and daily function and repeated this survey at serial intervals through 12 weeks post-operatively. Medical record review was performed to confirm demographic and obtain surgical data. RESULTS: Hierarchical generalized linear models were used to model the trajectory of pain, well-being and satisfaction over the course of the post-surgical period. Subanalysis including only laparoscopic cases was performed. There was no difference in satisfaction (p = 0.48, OR 0.80 [CI 95% 0.43, 1.48]), well-being (p = 0.55, OR 1.12 [CI 95% 0.84, 1.79]), or dyspareunia (p = 0.57, OR 0.75 [CI 95% 0.27, 2.04]) scores between laparoscopic/robotic supracervical and total hysterectomy groups. This was unchanged when all hysterectomy approaches were included in analysis. Cervix removal was associated with higher pain scores with all surgical approaches although this did not reach statistical significance. CONCLUSIONS: Patient-centered outcomes suggest overall equivalent tolerance of supracervical and total hysterectomy procedures with a trend towards short-term pain improvement with cervical retention.

Temporal dynamics of neurobehavioral hormone sensitivity in a scaled-down experimental model of early pregnancy and parturition.

The hormonal changes of pregnancy and parturition can trigger robust changes in affective state, particularly among patients with a history of postpartum depression. However, more work is needed to elucidate the temporal dynamics of symptom emergence. The current study explored how quickly hormone-sensitive (HS+) individuals can be differentiated from hormone-insensitive (HS-) controls in the context of a tightly controlled experimental hormone manipulation, and which symptoms demonstrate the most rapid, consistent, and largest response during this protocol. Participants were female, non-pregnant, and euthymic, with a history of DSM-5 major depressive episode with peripartum onset (n = 15) or parous healthy controls with no psychiatric history (n = 15). Perinatal hormonal changes were simulated by inducing hypogonadism, adding back estradiol (E2) and progesterone (P4) to reach first-trimester levels for 8 weeks, and then subsequently withdrawing both hormones. Those reporting a 30% or greater increase during addback or withdrawal on select subscales of the Inventory of Depression and Anxiety Symptoms (IDAS) were identified as HS+. Participants provided daily ratings of symptoms throughout the study via the Daily Record of Severity of Problems. Results indicated that HS+ participants could be differentiated from HS- participants early in the hormone protocol, with many symptoms showing significantly greater change from baseline within the first week of addback. Notably, the most rapid symptom increases were observed for Anger/Irritability, Mood Swings, Overwhelm, Lethargy, Increased Appetite, Joint and Muscle Pain, and Breast Tenderness, reaching 50% of peak group contrast within the first week of hormone addback. The largest group effects were observed for Anger/Irritability, followed by Fatigue and Anxiety, and the most consistent group effects were observed for Anger/Irritability, Interpersonal Conflict, Overwhelm, and Hopelessness. Findings support the role of reproductive hormones in the onset of perinatal affective disorders. The rapid emergence of anger and irritability in HS+ participants suggests that these symptoms may be early indicators of perinatal hormone sensitivity.

Brief Report: Under-Identification of Symptomatic Menopause in Publicly-Insured Autistic People.

Menopause is a normal part of aging and in the general population is associated with chronic conditions that impact health, mortality, and well-being. Menopause is experienced differently by autistic individuals, although no studies have investigated this topic in a large sample. The purpose of this study was to investigate rates of, and factors associated with symptomatic menopause among autistic individuals and to identify the prevalence of co-occurring conditions in symptomatic individuals. We included autistic females aged 35-70 years enrolled for 10 + months in 2014-2016 Medicare and/or Medicaid (n = 26,904), excluding those with gender dysphoria. Those with symptomatic menopause were compared to a non-symptomatic reference group on demographic, enrollment characteristics, and co-occurring conditions through logistic regression. Approximately 4% of publicly-insured autistic females aged 46-70 years had symptomatic menopause in their medical records. Intellectual disability was associated with a lower likelihood of symptomatic menopause, and being Medicare-enrolled or dual-enrolled was associated with higher likelihood of having symptomatic menopause recorded. In adjusted models, rates of ADHD, anxiety and depressive disorders, headache/migraine, altered sensory experiences, altered sexual function, and sleep disturbance were significantly higher in the symptomatic menopause sample compared to the reference group. More work to better support autistic women in discussing menopausal symptoms and co-occurring conditions with primary care providers is needed, particularly among those for whom self-report of symptoms are more challenging to ascertain. Factors associated with specific types of health care coverage warrant greater investigation to support better identification.

WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis.

Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood. Here, we used single-molecule tracking (SMT) in combination with a WRN inhibitor to examine WRN dynamics within the nuclei of living cancer cells. WRN inhibition traps the helicase on chromatin, requiring p97/VCP for extraction and proteasomal degradation in a MSI-H dependent manner. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation. Finally, we show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells and confirm the in vivo activity of WRN inhibition using an MSI-H mouse xenograft model. This work elucidates a regulatory mechanism for WRN that may facilitate identification of new therapeutic modalities, and highlights the use of SMT as a tool for drug discovery and mechanism-of-action studies.

Credentialing and Patient Safety in Robotic Gynecologic Surgery: Changes over the Last Eight Years.

Background and Objectives: Robotic gynecologic surgery has outpaced data showing risks and benefits related to cost, quality outcomes, and patient safety. We aimed to assess how credentialing standards and perceptions of safe use of robotic gynecologic surgery have changed over time. Methods: An anonymous, online survey was distributed in 2013 and in 2021 to attending surgeons and trainees in accredited obstetrics and gynecology residency programs. Results: There were 367 respondents; 265 in 2013 and 102 in 2021. There was a significant increase in robotic platform use from 2013 to 2021. Percentage of respondents who ever having performed a robotic case increased from 48% to 79% and those who performed > 50 cases increased from 25% to 59%. In 2021, a greater percentage of attending physicians reported having formalized protocol for obtaining robotic credentials (93% vs 70%, p = 0.03) and maintaining credentialing (90% vs 27%, p < 0.01). At both time points, most attendings reported requiring proctoring for 1 - 5 cases before independent use. Opinions on the number of cases needed for surgical independence changed from 2013 to 2021. There was an increase in respondents who believed > 20 cases were required (from 58% to 93% of trainees and 29% to 70% of attendings). In 2021, trainees were less likely to report their attendings lacked the skills to safely perform robotic surgery (25% to 6%, p < 0.01). Discussion: Greater experience with robotic platforms and expansion of credentialing processes over time correlated with improved confidence in surgeon skills. Further work is needed to evaluate if current credentialing procedures are sufficient.

Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs): study protocol for a neural and molecular mechanistic clinical trial.

BACKGROUND: The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis. METHODS: This study will recruit 100 unmedicated women ages 44-55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith-Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment. DISCUSSION: This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282277.