Comparing endometrial biopsy results with hysteroscopic pathology in women presenting with abnormal and postmenopausal uterine bleeding.

OBJECTIVE: To compare pathology results after office-based blind endometrial biopsy and pathology results from hysteroscopy in women presenting with abnormal uterine bleeding (AUB). METHODS: A retrospective cohort study of biologic women presenting with AUB at a tertiary care referral care center. Patients were included if they underwent evaluation with blind endometrial biopsy performed in the office followed by hysteroscopy within one year. Hysteroscopic findings and pathology were correlated with index endometrial biopsy findings. RESULTS: 689 patients met inclusion criteria. The mean age and BMI were 49 (±10) years and 31 (±8) kg/m2. The median duration of bleeding leading up to presentation was of 3.5 (1.5-9) months. Of the patients who had operative hysteroscopic pathology demonstrating endometrial polyp, 30.6 % (81) had a polyp detected on office endometrial biopsy. Of the patients who had hysteroscopic pathology demonstrating intracavitary fibroids, 0 % (0) were detected on endometrial biopsy. Of the patients who had hyperplasia without atypia on hysteroscopy, 28.6 % (4) were detected or suspected on endometrial biopsy. Of the patients who had hyperplasia with atypia on hysteroscopy, 5.9 % (1) were detected or suspected on endometrial biopsy. There were 12 cases of confirmed or suspected malignancy on hysteroscopy, of which 8.3 % (1) were detected on endometrial biopsy. CONCLUSION: Concordance between focal findings on office hysteroscopy and endometrial biopsy is low. Endometrial biopsy when malignancy is suspected has been shown to be of benefit, but in the setting of suspected benign focal pathology, blind assessment of the endometrial cavity for definitive diagnosis should be abandoned. In women with symptomatic uterine bleeding, hysteroscopic visualization is associated with increased sensitivity in identifying intrauterine pathology.

Diagnostic considerations and surgical techniques for a large prolapsing submucosal myoma.

OBJECTIVE: To review important diagnostic considerations for accurate identification of a prolapsing submucosal myoma and to highlight surgical techniques for minimally invasive and uterine-sparing combined vaginal and hysteroscopic myomectomy. Submucosal myomas can present with various symptoms, including vaginal bleeding, pelvic pain, and abnormal discharge, and can also contribute to infertility. This type of myoma has the potential to prolapse through the cervical canal, and prompt identification and management are essential to avoid serious sequelae, including hemorrhage, infection, and sepsis. DESIGN: A case report. Patient consent was received to publish. This publication received an exemption from institutional review board approval from the institution as this was a case report. The investigators have no conflicts of interest. SETTING: Academic medical center. PATIENTS: We present a 33-year-old G5P2032 patient with pelvic pain and vaginal bleeding. Her clinical course involved multiple encounters with inaccurate diagnoses, leading to worsening symptoms. She was found ultimately to have a large, prolapsing submucosal myoma. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, and others), and other applicable sites. INTERVENTION(S): Given the severity of her symptoms and her desire for uterine preservation for future fertility, the patient was counseled on the need for surgical intervention and elected to proceed with a combined vaginal and hysteroscopic myomectomy. MAIN OUTCOME MEASURE(S): Preoperative considerations discussed in this video include common mimics of this condition, the importance of a thorough pelvic examination and preoperative imaging, as well as recommendations for surgical management. RESULT(S): We reviewed the following surgical techniques: (1) adequate exposure; (2) clamping of the myoma stalk; (3) morcellation "cone" technique; (4) use of intracervical vasopressin; (5) hysteroscopic evaluation; and (6) insertion of an intrauterine balloon. CONCLUSION(S): Prolapsing submucosal myomas can present as common gynecologic complaints but can lead to serious sequelae when timely diagnosis and treatment are not performed. Appropriate evaluation, accurate diagnosis, preoperative imaging, and knowledge of surgical techniques are critical for optimizing patient outcomes and avoiding complications in patients with a prolapsed myoma.

PSGL-1 attenuates early TCR signaling to suppress CD8+ T cell progenitor differentiation and elicit terminal CD8+ T cell exhaustion.

PSGL-1 (P-selectin glycoprotein-1) is a T cell-intrinsic checkpoint regulator of exhaustion with an unknown mechanism of action. Here, we show that PSGL-1 acts upstream of PD-1 and requires co-ligation with the T cell receptor (TCR) to attenuate activation of mouse and human CD8+ T cells and drive terminal T cell exhaustion. PSGL-1 directly restrains TCR signaling via Zap70 and maintains expression of the Zap70 inhibitor Sts-1. PSGL-1 deficiency empowers CD8+ T cells to respond to low-affinity TCR ligands and inhibit growth of PD-1-blockade-resistant melanoma by enabling tumor-infiltrating T cells to sustain an elevated metabolic gene signature supportive of increased glycolysis and glucose uptake to promote effector function. This outcome is coupled to an increased abundance of CD8+ T cell stem cell-like progenitors that maintain effector functions. Additionally, pharmacologic blockade of PSGL-1 curtails T cell exhaustion, indicating that PSGL-1 represents an immunotherapeutic target for PD-1-blockade-resistant tumors.

The Impact of Fertility Goals on Long-term Quality of Life in Reproductive-aged Women Who Underwent Myomectomy versus Hysterectomy for Uterine Fibroids.

STUDY OBJECTIVE: The objective of this study is to compare quality of life (QOL) for myomectomy with hysterectomy 1 to 5 years after surgical management for fibroids. This study evaluated the difference in QOL in a population of women of reproductive age, including those who desire fertility. DESIGN: A retrospective cohort study. INTERVENTIONS: Not applicable. SETTING: A large academic hospital. PATIENTS: A total of 142 women who underwent hysterectomy or myomectomy in 2015 to 2020. Included patients were women aged 18 years or older who underwent surgical intervention owing to uterine fibroids. MEASUREMENTS AND MAIN RESULTS: The 36-Item Short Form Health Survey (SF-36) provides a total score as a single measure of health-related QOL. The Uterine Fibroid Symptom Quality of Life Questionnaire for Hysterectomy and Myomectomy (UFS-QOL) is a patient-reported outcome measure of fibroid symptoms and health-related QOL after hysterectomy and myomectomy. There was no significant difference in SF-36 QOL scores in women after myomectomy who desired fertility compared with those who did not desire fertility, except in the social functioning domain (p = .025). UFS-QOL scores in women after myomectomy who desired fertility were not significantly different compared with women after myomectomy who did not desire fertility (p = .37). There were no significant differences between women who underwent myomectomy and hysterectomy in overall QOL scores on the SF-36 (p = .13) and UFS-QOL scores (p = .16). CONCLUSION: Myomectomy is not associated with significant differences in measures of general health and QOL compared with hysterectomy, making it a viable fibroid management option for women who desire fertility. Our study highlights the importance of discussing fertility goals and QOL when counseling patients for surgical fibroid treatment.

Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma.

Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to therapy. Here, we characterize the function of the ubiquitin ligases Siah1a/2 in regulating the differentiation and activity of alveolar macrophages (AM) and assess the implication of Siah1a/2 control of AMs for carcinogen-induced LUAD. Macrophage-specific genetic ablation of Siah1a/2 promoted accumulation of AMs with an immature phenotype and increased expression of protumorigenic and pro-inflammatory Stat3 and ß-catenin gene signatures. Administration of urethane to wild-type mice promoted enrichment of immature-like AMs and lung tumor development, which was enhanced by macrophage-specific Siah1a/2 ablation. The profibrotic gene signature seen in Siah1a/2-ablated immature-like macrophages was associated with increased tumor infiltration of CD14+ myeloid cells and poorer survival of patients with LUAD. Single-cell RNA-seq confirmed the presence of a cluster of immature-like AMs expressing a profibrotic signature in lungs of patients with LUAD, a signature enhanced in smokers. These findings identify Siah1a/2 in AMs as gatekeepers of lung cancer development. SIGNIFICANCE: The ubiquitin ligases Siah1a/2 control proinflammatory signaling, differentiation, and profibrotic phenotypes of alveolar macrophages to suppress lung carcinogenesis.

Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities.

Immune suppressive factors of the tumor microenvironment (TME) undermine viability and exhaust the activities of the intratumoral cytotoxic CD8 + T lymphocytes (CTL) thereby evading anti-tumor immunity and decreasing the benefits of immune therapies. To counteract this suppression and improve the efficacy of therapeutic regimens, it is important to identify and understand the critical regulators within CD8 + T cells that respond to TME stress and tumor-derived factors. Here we investigated the regulation and importance of activating transcription factor-4 (ATF4) in CTL using a novel Atf4ΔCD8 mouse model lacking ATF4 specifically in CD8 + cells. Induction of ATF4 in CD8 + T cells occurred in response to antigenic stimulation and was further increased by exposure to tumor-derived factors and TME conditions. Under these conditions, ATF4 played a critical role in the maintenance of survival and activities of CD8 + T cells. Conversely, selective ablation of ATF4 in CD8 + T cells in mice rendered these Atf4ΔCD8 hosts prone to accelerated growth of implanted tumors. Intratumoral ATF4-deficient CD8 + T cells were under-represented compared to wild-type counterparts and exhibited impaired activation and increased apoptosis. These findings identify ATF4 as an important regulator of viability and activity of CD8 + T cells in the TME and argue for caution in using agents that could undermine these functions of ATF4 for anti-cancer therapies.

Resolving the conflicts around Par2 opposing roles in regeneration by comparing immune-mediated and toxic-induced injuries.

BACKGROUND: Different factors may lead to hepatitis. Among which are liver inflammation and poisoning. We chose two hepatitis models, typical for these two underlying causes. Thus, we aimed to characterize the role of protease-activated receptor 2 (Par2) in liver regeneration and inflammation to reconcile Par2 conflicting role in many damage models, which sometimes aggravates the induced damage and sometimes alleviates it. METHODS: WT and knockout (Par2KO) mice were injected with concanavalin A (ConA) to induce immune-mediated hepatitis or with carbon tetrachloride (CCl4) to elicit direct hepatic damage. To distinguish the immune component from the liver regenerative response, we conducted bone marrow (BM) replacements of WT and Par2KO mice and repeated the damage models. RESULTS: ConA injection caused limited damage in Par2KO mice livers, while in the WT mice severe damage followed by leukocyte infiltration was evident. Reciprocal BM replacement of WT and Par2KO showed that WT BM-reconstituted Par2KO mice displayed marked liver damage, while in Par2KO BM-reconstituted WT mice, the tissue was generally protected. In the CCl4 direct damage model, hepatocytes regenerated in WT mice, whereas Par2KO mice failed to recover. Reciprocal BM replacement did not show significant differences in hepatic regeneration. In Par2KO mice, hepatitis was more apparent, while WT recovered regardless of the BM origin. CONCLUSIONS: We conclude that Par2 activation in the immune system aggravates hepatitis and that Par2 activation in the damaged tissue promotes liver regeneration. When we incorporate this finding and revisit the literature reports, we reconciled the conflicts surrounding Par2's role in injury, recovery, and inflammation.

Faith Community Nurses Making a Difference for Older African Americans in a Pandemic.

ABSTRACT: During and after COVID-19, African Americans experienced a disparate amount of social isolation and loneliness and subsequent increases in morbidity and mortality. Faith community nurses are equipped to assist community providers, health practitioners, and local officials in addressing gaps in older African Americans' financial, social, physical, and spiritual needs during social distancing.

Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials.

BACKGROUND: Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs. Linzagolix is an oral gonadotropin-releasing hormone receptor antagonist taken once per day that dose-dependently suppresses gonadal steroids and might reduce uterine-fibroid-associated signs. Two phase 3 trials were conducted to confirm the efficacy and safety of linzagolix at full-suppression (200 mg) and partial-suppression (100 mg) doses with or without hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate) compared with placebo for the treatment of symptomatic uterine fibroids. METHODS: PRIMROSE 1 and PRIMROSE 2 were identical 52-week, randomised, parallel, double-blind, placebo-controlled, phase 3 trials conducted at clinics in the USA (PRIMROSE 1) and Europe and the USA (PRIMROSE 2). Eligible women with uterine fibroid-associated heavy menstrual bleeding (menstrual blood loss >80 mL per cycle) were randomly assigned in a 1:1:1:1:1 ratio to one of five masked treatments: (1) placebo, (2) 100 mg linzagolix per day alone, (3) 100 mg linzagolix per day with once-per-day hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate), (4) 200 mg linzagolix per day alone, or (5) 200 mg linzagolix per day with once-per-day hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate). The primary endpoint was a response (menstrual blood loss ≤80 mL and ≥50% reduction from baseline) at 24 weeks in women who received at least one dose of treatment and did not meet any exclusion criteria based on predosing assessments. These trials are registered with ClinicalTrials.gov (NCT03070899 and NCT03070951). The trials have been completed. FINDINGS: Between May, 2017, and October, 2020, in PRIMROSE 1, 574 women were enrolled, of which 48 discontinued and 15 were excluded; therefore, 511 women were included in the full analysis set; and in PRIMROSE 2, 535 women were enrolled, of which 24 did not receive the study drug and ten women were excluded from the study, resulting in 501 women being included in the full analysis set. In both trials, a significantly higher proportion of women had a reduction in heavy menstrual bleeding in all linzagolix (with or without add-back therapy) treatment groups compared with the placebo group (p≤0·003). In PRIMROSE 1, the response rates were 56·4% (95% CI 45·8-66·6%) in the 100 mg group, 66·4% (56·6-75·2%) in the 100 mg plus add-back therapy group, 71·4% (61·8-79·8%) in the 200 mg group, and 75·5% (66·0-83·5%) in the 200 mg plus add-back therapy group, compared with 35·0% (25·8-45·0%) in the placebo group. In PRIMROSE 2, the response rates were 56·7% (46·3-66·7%) in the 100 mg group, 77·2% (67·8-85·0%) in the 100 mg plus add-back therapy group, 77·7% (68·4-85·3%) in the 200 mg group, and 93·9% (87·1-97·7%) in the 200 mg plus add-back therapy group, compared with 29·4% (20·8-39·3%) with placebo. The most common adverse events up to 24 weeks were hot flushes (35% of participants in PRIMROSE 1 and 32% in PRIMROSE 2 with linzagolix [200 mg] alone and 3-14% in all other groups). INTERPRETATION: Linzagolix (100 mg or 200 mg) with or without add-back therapy significantly reduced heavy menstrual bleeding. Partial suppression with once-per-day linzagolix (100 mg) without add-back therapy potentially provides a unique option for the chronic treatment of symptomatic uterine fibroids in women who cannot or do not want to take concomitant hormonal add-back therapy. FUNDING: ObsEva.

Implementation of Office Hysteroscopy for the Evaluation and Treatment of Intrauterine Pathology.

Hysteroscopy provides a minimally invasive strategy to evaluate intrauterine pathology and manage conditions such as abnormal uterine bleeding, infertility, intrauterine adhesions, müllerian anomalies, and intrauterine foreign bodies. Increasing access to hysteroscopy procedures in the office has the potential to improve patient care by minimizing financial and logistical barriers, aiding in streamlined diagnosis and treatment planning, and potentially averting unnecessary operative procedures and anesthesia. Office hysteroscopy refers to procedures performed in outpatient settings where pain management involves no medications, oral nonsedating medications, local anesthetic agents, or oral or inhaled conscious sedation. We present best practices for the implementation of hysteroscopy in an office setting. These include appropriate patient selection, optimal procedural timing, cervical preparation for patients at highest risk of cervical stenosis or pain with dilation, individualized pain-management strategies, use of distension media, and video monitoring to engage patients in the procedure. We describe miniaturized equipment for use in the office setting and "no-touch" vaginoscopic approaches to limit patient discomfort. With appropriate training and experience, office hysteroscopy presents a simple and cost-effective modality for optimizing gynecologic care for our patients.

Racial and ethnic disparities in surgical care for endometriosis across the United States.

BACKGROUND: Despite an estimated 10% prevalence of endometriosis among reproductive-age women, surgical population-based data are limited. OBJECTIVE: We sought to investigate racial and ethnic disparities in surgical interventions and complications among patients undergoing endometriosis surgery across the United States. STUDY DESIGN: We performed a retrospective cohort study of American College of Surgeons National Surgical Quality Improvement Program data from 2010 to 2018 identifying International Classification of Diseases, Ninth/Tenth Revision codes for endometriosis We compared procedures, surgical routes (laparoscopy vs laparotomy), and 30-day postoperative complications by race and ethnicity. RESULTS: We identified 11,936 patients who underwent surgery for endometriosis (65% White, 8.2% Hispanic, 7.3% Black or African American, 6.2% Asian, 1.0% Native Hawaiian or Pacific Islander, 0.6% American Indian or Alaska Native, and 11.5% of unknown race). Perioperative complications occurred in 9.6% of cases. After adjusting for confounders, being Hispanic (adjusted odds ratio, 1.31; 95% confidence interval, 1.06-1.64), Black or African American (adjusted odds ratio, 1.71; confidence interval, 1.39-2.10), Native Hawaiian or Pacific Islander (adjusted odds ratio, 2.08; confidence interval, 1.28-3.37), or American Indian or Alaska Native (adjusted odds ratio, 2.34; confidence interval, 1.32-4.17) was associated with surgical complications. Hysterectomies among Hispanic (adjusted odds ratio, 1.68; confidence interval, 1.38-2.06), Black or African American (adjusted odds ratio, 1.77; confidence interval, 1.43-2.18), Asian (adjusted odds ratio, 1.87; confidence interval, 1.43-2.46), Native Hawaiian or Pacific Islander (adjusted odds ratio, 4.16; confidence interval, 2.14-8.10), and patients of unknown race or ethnicity (adjusted odds ratio, 2.07; confidence interval, 1.75-2.47) were more likely to be open. Being Hispanic (adjusted odds ratio, 1.64; confidence interval, 1.16-2.30) or Black or African American (adjusted odds ratio, 2.64; confidence interval, 1.95-3.58) was also associated with receipt of laparotomy for nonhysterectomy procedures. The likelihood of undergoing oophorectomy was increased for Hispanic and Black women (adjusted odds ratio, 2.57; confidence interval, 1.96-3.37 and adjusted odds ratio, 2.06; confidence interval, 1.51-2.80, respectively), especially at younger ages. CONCLUSION: Race and ethnicity were independently associated with surgical care for endometriosis, with elevated complication rates experienced by Hispanic, Black or African American, Native Hawaiian or Pacific Islander, and American Indian or Alaska Native patients.

A Call-to-Action for Clinicians to Implement Evidence-Based Best Practices When Caring for Women with Uterine Fibroids.

Uterine fibroids are common benign tumors that occur in up to 80% of women. Approximately half of the women affected experience considerable physical, psychological, and economic burdens and impact on quality of life due to symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. Several medical and surgical options are available to treat uterine fibroids; however, healthcare providers may benefit from practical guidance in the development of individualized treatment plans based on a personalized approach. Medical treatments and minimally invasive procedures are generally preferred by most patients before considering more invasive, higher risk surgical interventions. In general, patient-centered, uterine-preserving procedures may be prioritized based on the patient's goals and the clinical scenario. Occasionally, hysterectomy may be the preferred treatment option for some patients who require definitive treatment. This call-to-action highlights recent challenges to patient care, including radical shifts in physician-patient interactions due to the COVID-19 pandemic and recent changes to evidence-based, clinically approved therapies. This report also reviews contemporary recommendations for women's health providers in the diagnosis and medical and surgical management of uterine fibroids. This call-to-action aims to empower healthcare providers to optimize the quality of care for women with uterine fibroids utilizing the best available evidence and best practices.

MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8+ T Cell Responses.

MicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8+ T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8+ CTLs compared with naive CD8+ T cells. One miRNA found to be highly downregulated on both strands in effector CTLs was miR-139. Because previous studies have indicated a role for miR-139-mediated regulation of CTL effector responses, we hypothesized that deletion of miR-139 would enhance antiviral CTL responses during influenza virus infection. We generated miR-139-/- mice or overexpressed miR-139 in T cells to assess the functional contribution of miR-139 expression in CD8+ T cell responses. Our study demonstrates that the development of naive T cells and generation or differentiation of effector or memory CD8+ T cell responses to influenza virus infection are not impacted by miR-139 deficiency or overexpression; yet, miR-139-/- CD8+ T cells are outcompeted by wild-type CD8+ T cells in a competition setting and demonstrate reduced responses to Listeria monocytogenes Using an in vitro model of T cell exhaustion, we confirmed that miR-139 expression similarly does not impact the development of T cell exhaustion. We conclude that despite significant downregulation of miR-139 following in vivo and in vitro activation, miR-139 expression is dispensable for influenza-specific CTL responses.

Uterine Fibroids in Black Women: A Race-Stratified Subgroup Analysis of Treatment Outcomes After Laparoscopic Radiofrequency Ablation.

Background: The disease and treatment burden of uterine fibroids (UF) in Black women is substantially greater compared with other racial groups, with higher rates of complications and poorer outcomes with both hysterectomy and myomectomy. The inequities in the access Black women have to minimally invasive routes of surgery contribute to their burden of illness. Laparoscopic radiofrequency ablation (LAP-RFA) is a minimally invasive, safe, and effective uterine-sparing treatment option. Methods: This subgroup analysis of the LAP-RFA Pivotal Trial stratified outcomes by race comparing White women (n = 28, 21%) versus Black women (n = 46, 34%). Results: At baseline, Black women had more fibroids on average (7.3 vs. 3.7; P ≤ 0.001), a greater symptom severity score (SSS) (P ≤ 0.001), and a lower health-related quality of life (HRQoL) score (P = 0.005) than White women. At 36 months post-treatment with LAP-RFA, the statistical differences that existed with baseline SSS and HRQoL score were eliminated between Black and White women. Menstrual blood loss (140.1 mL vs. 127.02 mL; P = 0.44) and mean fibroid volume reduction (47.5 cm3 vs. 36.0 cm3; P = 0.17) were similar between Black and White women at 12 months. Although not statistically significant, the intraoperative total blood loss and uterine blood loss was lower in Black women than White women, despite greater operative time (160 minutes vs. 137 minutes; P = 0.09). Conclusions: These results are promising in providing an alternative uterine-sparing option for Black women and may help to provide a minimally invasive option that can address some of the racial inequities in care for Black women with UF.

A most vulnerable population: Black men.

Black men disproportionately experience the worst health outcomes among U.S. populations. Systemic social, political, and healthcare problems are important intersecting issues of Black men's poor health outcomes. As nursing is one of the most trusted professions, it is nurses' responsibilities to include care for vulnerable populations. In this creative controversy an alternative perspective of Black men as a vulnerable population is proposed. Potential tensions and an introspective call to action for all nurses is included.

International Consensus Statement for Recommended Terminology Describing Hysteroscopic Procedures.

OBJECTIVE: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research. DESIGN: Open forum discussion followed by online video meetings. SETTING: International community of hysteroscopy experts PATIENTS: Not applicable. INTERVENTIONS: Series of online video meetings to complete a previously established agenda until a final agreement for standardized nomenclature was obtained. MEASUREMENT AND MAIN RESULTS: The adoption and implementation of a common terminology to standardize reporting of hysteroscopic procedures was proposed to cover five domains: pain management, healthcare setting, model of care, type of hysteroscopic procedure and the hysteroscopic approach to the uterine cavity. A final agreement was obtained after 3 online video meetings. CONCLUSION: Hysteroscopy is the gold standard technique for the evaluation and management of uterine disorders. A clear definition and understanding of the terminology used to describe hysteroscopic procedures is lacking. The production of this international consensus statement for terminology to describe hysteroscopic procedures, covering pain management, setting, model of care, type of procedure and hysteroscopic approach, has the potential to enable more effective communication for both clinical and research purposes with the ultimate aim of improving patient care and clinical outcomes.

Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.

Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.