Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Distribution of Nerve Fibers in Abdominal Wall Endometriosis and Their Clinical Significance.

Objective: This study aimed to explore the distribution of nerve fibers in abdominal wall endometriosis (AWE) and discern their association with pain. Methods: A retrospective case-control study was conducted. The cases comprised 30 patients diagnosed with AWE, while the control group consisted of 17 patients who had undergone laparotomy without any history of endometriosis. We analyzed clinical characteristics and examined the innervation patterns in samples using stains for S-100, neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), neurofilament (NF), and substance P (SP) antibodies. Results: There was a notable increase in the density of S-100, NSE and PGP9.5 immunoreactive nerve fibers and a higher proportion of SP positivity in AWE lesions compared to standard abdominal wall scars (p < 0.05). However, there were no significant differences in the density or proportion of NF-immunoreactive nerve fibers between the cases and the controls. Moreover, no statistically significant correlation was observed between the density of S-100, NSE, PGP9.5, NF, or SP-positive nerve fibers and pain scores. Conclusion: This study demonstrated an increased immunoreactive nerve fiber density located in AWE lesions compared to normal abdominal wall scars. Further high-quality studies are needed to investigate the mechanisms responsible for pain in women with endometriosis.

Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma.

Background: The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Methods: Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Results: Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Conclusion: Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.

The pathogenesis of endometriosis and adenomyosis: insights from single-cell RNA sequencing†.

Endometriosis and adenomyosis are two similar gynecological diseases that are characterized by ectopic implantation and the growth of the endometrial tissue. Previous studies have reported that they share a common pathophysiology in some respects, such as a similar cellular composition and resistance to the progestogen of lesions, but their underlying mechanisms remain elusive. Emerging single-cell ribonucleic acid sequencing (scRNA-seq) technologies allow for the dissection of single-cell transcriptome mapping to reveal the etiology of diseases at the level of the individual cell. In this review, we summarized the published findings in research on scRNA-seq regarding the cellular components and molecular profiles of diverse lesions. They show that epithelial cell clusters may be the vital progenitors of endometriosis and adenomyosis. Subclusters of stromal cells, such as endometrial mesenchymal stem cells and fibroblasts, are also involved in the occurrence of endometriosis and adenomyosis, respectively. Moreover, CD8+ T cells, natural killer cells, and macrophages exhibit a deficiency in clearing the ectopic endometrial cells in the immune microenvironment of endometriosis. It seems that the immune responses are activated in adenomyosis. Understanding the immune characteristics of adenomyosis still needs further exploration. Finally, we discuss the application of findings from scRNA-seq for clinical diagnosis and treatment. This review provides fresh insights into the pathogenesis of endometriosis and adenomyosis as well as the therapeutic targets at the cellular level.

Clinical features of patients with previous spontaneous rupture of ovarian endometrioma operated electively: a case-control study.

BACKGROUND: The aim of the study is to investigate the proportion and clinical features of previous spontaneously ruptured ovarian endometrioma among women who underwent elective surgery for endometrioma. METHODS: This retrospective study was based on a cohort of elective surgeries for endometrioma performed by the same gynecologic team at Peking Union Medical College Hospital from January 2017 to October 2022. Patients diagnosed with previous spontaneously ruptured endometrioma during elective surgery were enrolled in the ruptured group. In the same cohort, patients with unruptured endometrioma treated during the same period were selected as the unruptured group by 1:2 matching according to age. Demographic and clinical information were collected and compared between two groups. RESULTS: A total of 422 patients in the cohort were diagnosed with endometrioma. There were 38 patients (9.0%) in ruptured group and 76 patients in unruptured group. All enrolled participants were treated by laparoscopic surgery. In ruptured group, 86.8% patients had a history of acute abdominal pain, which was only 13.2% in unruptured group (P < 0.001). Compared to unruptured group, patients diagnosed with ruptured endometrioma had a lower BMI (P = 0.021), larger maximum diameter of endometrioma (P = 0.040), higher proportion of cul-de-sac partial obliteration rather than complete obliteration (P = 0.003). CONCLUSIONS: Spontaneous rupture of endometrioma is not rare. The proportion of spontaneous rupture of endometrioma in our study was higher than that reported in the literatures. In women with endometrioma, the onset of acute abdominal pain should be considered a rupture of cyst, especially in patients with big cysts.

Effects of localization of uterine adenomyosis on clinical features and pregnancy outcome.

The purpose of this study was to implore the association among clinical features, long-term fertility outcomes and the anatomical location of adenomyosis identified by ultrasound. We collected data of non-pregnant patients between 20 and 40 years old who had undergone surgical exploration for benign gynecological conditions at our institution between January 2010 and December 2017. A total of 158 women met the inclusion criteria and were allocated into three groups according to the ultrasound-determined adenomyosis anatomical location: anterior (Group A), posterior (Group B), both posterior and anterior (Group C). 44.3% (70/158) adenomyosis was located at the posterior side. History of miscarriage and parity were significantly higher in Group C (p = 0.036 and 0.001 respectively). Group C also had a higher concurrence rate of ovarian endometrioma (OEM) (80.4%, p = 0.002), pelvic adhesion (80.4%, P = 0.003) and the revised American Fertility Society (rAFS) Score (median64, range2-100, P < 0.001), while a significantly lower rate of concurrent peritoneal endometriosis (P = 0.01). Group B showed a relative higher rate of coexistent heavy menstrual bleeding (28.6%, p = 0.04) and oviduct obstruction (24.3%, P = 0.038). Group A had a higher proportion of coexistent leiomyoma (53.1%, P = 0.002). There were no significant differences between group A, B, and C in terms of pain symptoms, endometrial polyps, operation time, and endometriosis fertility index score and other basic characters (p > 0.05). During the follow-up, 59.2% (61/103) patients had clinical pregnancies, and 26.2% (16/61) of them experienced pregnancy loss. Total in vitro fertilization and embryo transfer pregnancy rate was 64.6% (42/65) and spontaneous pregnancy rate was 50.0% (19/38). The Kaplan-Meier curves demonstrated significant lower cumulative pregnancy rate in Group C than Group A and Group B (p = 0.01). Severe obstetric complications such as placenta previa, placenta accreta, preeclampsia, and preterm birth were only found in women with adenomyosis located in the posterior side. In conclusion, types of adenomyosis based on sonographic location had different clinical features and pregnancy outcome. Patients with adenomyosis lesion in both anterior and posterior sides had higher combination of OEM, pelvic adhesion and rAFS score.

Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures.

The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.

Bedquiline Resistance Mutations: Correlations with Drug Exposures and Impact on the Proteome in M. tuberculosis.

Bedaquiline (BDQ) is an effective drug for the treatment of drug-resistant tuberculosis. Mutations in atpE, which encodes the target of BDQ, are associated with large increases in MICs. Mutations in Rv0678 that derepress the transcription of the MmpL5-MmpS5 efflux transporter are associated with smaller increases in MICs. However, Rv0678 mutations are the most common mutations that are associated with BDQ resistance in clinical isolates, and they also confer cross-resistance to clofazimine (CFZ). To investigate the mechanism of BDQ resistance and the correlation between Rv0678 mutations and target-based atpE mutations, M. tuberculosis strains were exposed to different concentrations of BDQ or CFZ to select Rv0678 mutations and atpE mutations. Gene overexpression strains were constructed to illustrate the roles of MmpL5 and MmpS5. A quantitative proteome analysis was performed to compare the BDQ-resistant mutants to the isogenic strain H37Rv. Here, we report that the Rv0678 mutations were more readily selected than were the atpE mutations at low concentrations of BDQ or CFZ. The atpE mutations were selected by high concentrations of BDQ exposure. The overexpression of both mmpL5 and mmpS5 reduced the susceptibility of Mycobacterium tuberculosis to BDQ and CFZ. Secreted immunogenic proteins and proteins involved in the biosynthesis and transport of phthiocerol dimycocerosates were associated with Rv0678 mutations conferring BDQ resistance in the proteome analysis. In conclusion, exposure to different bedaquiline concentrations resulted in the selection of different mutations. The coexpression of MmpL5 and MmpS5 contributed to drug resistance and upregulated pathogenic proteins in M. tuberculosis, suggesting MmpL5-MmpS5 as a new potential target for antituberculosis drug development. These results warrant further surveillance for the evolution of BDQ resistance during clinical usage.

The role of levonorgestrel-releasing intrauterine system for recurrence prevention after conservative surgery among patients with coexistent ovarian endometrioma and diffuse adenomyosis: A retrospective case control study with long-term follow up.

BACKGROUND: When ovarian endometrioma coexist with adenomyosis, the risk of postoperative recurrence increased. How is the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on symptomatic recurrence for those patients was unknown. METHODS: This study retrospectively analyzed 119 women with coexistent endometrioma and diffuse adenomyosis who received laparoscopic excision of pelvic endometriosis from January 2009 to April 2013. Women were categorized into two groups: intervention group with LNG-IUS and control group with expectant observation after surgery. Data were compared in terms of preoperative history, laboratory and intraoperative findings, and clinical outcomes during follow-up, including pain regression, changes in uterine volume and recurrence. RESULTS: During a median 79 months (range, 6-107) of follow-up, patients with LNG-IUS experienced a significantly lower symptomatic recurrence of either ovarian endometrioma or dysmenorrhea (11.1% vs. 31.1%, p = 0.013), compared with women under expectant observation by Kaplan-Meier survival analysis (χ2 = 5.448, p = 0.020) and Cox univariate assessment (hazard ratio of 0.336, 95% confidence interval 0.128-0.885, p = 0.027). Patients treated with LNG-IUS demonstrated a more prominent reduction in uterine volume (-14.1 ± 20.9 vs. 8.7 ± 48.8, p = 0.003) and higher percentage of complete pain remission (95.6% vs. 86.5%). For multivariate analysis, use of LNG-IUS (aHR 0.159, 95%CI 0.033-0.760, p = 0.021) and severity of dysmenorrhea (aHR 4.238, 95%CI 1.191-15.082, p = 0.026) were two independent factors associated with overall recurrence. CONCLUSION: Postoperative insertion of LNG-IUS may prevent recurrence in symptomatic women with comorbidity of ovarian endometrioma and diffuse adenomyosis.

The clinical features and long-term surgical outcomes of different types of abdominal wall endometriosis.

PURPOSE: To classify abdominal wall endometriosis (AWE) according to the invasive levels of tissue mass, and to compare the differences in clinical characteristics between different types of AWE. METHODS: In this study, we retrospectively analyzed the clinical data of 367 patients who had undergone resection of abdominal-wall endometriotic lesions at the Peking Union Medical College Hospital from January 2008 to December 2018, and we divided the patients into three types according to their deepest level of lesion invasion. Type I designated invasion of skin and subcutaneous tissue; type II, of fascia and rectus abdominis; and type III, of peritoneum. We classified, compared, and analyzed the general conditions, clinical manifestations, auxiliary examinations, surgical conditions, postoperative conditions, and recurrence status of patients. RESULTS: Of the 367 patients, type I patients accounted for 13.62%, type II patients for 56.68%, and type III for 29.7%. With respect to group comparisons, we observed that as the location of the mass deepened, the rate of concurrent pelvic endometriosis increased (P = 0.007), recurrent AWE was augmented (P = 0.02), the size of the mass increased (P < 0.001), the rate of multiple lesions became elevated (P < 0.001), the rate of mesh implantation increased (P < 0.001), the length of postoperative hospital stay (P < 0.001) was lengthened, the number of postoperative fever cases (P = 0.006) increased, and the risk of drainage placement (P < 0.001) was enhanced. The 5-year cumulative recurrence rate was 3.3%, and there was no significant difference in the recurrence rate among various types of AWE. CONCLUSION: Type III AWE carries more severe clinical manifestations, larger lesion size, longer operative time, greater intraoperative surgical difficulty, higher necessity of mesh implantation, and longer postoperative recovery process. Complete resection of AWE lesion is the main therapeutically approach and shows relatively low long-term recurrency rate.

Effects of aromatherapy and music therapy on patients' anxiety during MRI examinations: a randomized controlled trial.

OBJECTIVES: Many patients experience anxiety during MRI examinations. However, little attention has been focused on decreasing patient anxiety and minimizing on-site cancellations. Here, we aimed to investigate the effects of aromatherapy and music therapy on alleviating anxiety during MRI examinations. METHODS: This single-center, double-blinded, randomized control trial was conducted between November 1, 2021, and January 10, 2022. Patients undergoing MRI examinations were assigned randomly into either the aromatherapy group (AG), music therapy group (MG), aromatherapy plus music therapy group (AMTG), or routine care group (RG) at a ratio of 1:1:1:1. Aromatherapy was conducted through inhalation of lavender oil. Music therapy was performed using Pachelbel's Canon in D major. The primary outcome was the change in anxiety before and after the MRI scan, assessed using both the State-Trait Anxiety Inventory form 1 (STAI-1) and Self-Rating Anxiety Scale (SAS). The second outcome was the participant's comfort, measured using Kolcaba's General Comfort Questionnaire (GCQ). RESULTS: A total of 200 participants (mean age: 48.3 ± 14.9 years; 126 [63.0%] females) were enrolled, with 50 per group. The mean anxiety scores of the AMTG showed greater reduction compared with the AG, MG, and RG (ΔSTAI-1: 6.5 vs 2.6 vs 2.7 vs 1.9, p < 0.001; ΔSAS: 4.0 vs 1.4 vs 1.7 vs 0.6, p < 0.001). The mean GCQ score of the AMTG was higher compared with the AG, MG, and RG (98.0 vs 92.6 vs 91.2 vs 89.2, respectively, p < 0.001). CONCLUSION: Aromatherapy combined with music therapy is effective for reducing patients' anxiety and improving their comfort level during MRI scans. KEY POINTS: • In this randomized control trial of 200 participants undergoing MRI scans, aromatherapy plus music therapy is effective in reducing STAI-1 and SAS, as well as improving GCQ scores. • Although there was a significant difference between the aromatherapy plus music therapy and the single-intervention modalities, no significant differences were observed between the aromatherapy and music therapy themselves for state anxiety and comfort score. • Aromatherapy plus music therapy is a safe, non-invasive, nonpharmacological, and inexpensive patient-centered intervention for reducing anxiety and improving comfort in adults undergoing MRI examinations.

Experience of patients with diabetic retinopathy: A qualitative study.

AIMS: To understand the status quo and needs of self-management of patients with diabetic retinopathy (DR) and to provide a reference for formulating management programs that meet the needs of these patients. DESIGN: A qualitative interview study. METHODS: Semi-structured, in-depth interviews were conducted between November and December 2021. A purposive sample of 15 patients with DR who were hospitalized in the Retinal Department of Eye Hospital was recruited. Colaizzi's analysis was used to organize and analyse the interview data. This study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. RESULTS: The experience of patients with DR can be summarized into four themes: (1) lack of DR knowledge, (2) low quality of life, (3) poor self-management behaviour and (4) seek for support from many aspects. CONCLUSION: Patients with DR lack disease knowledge and have poor self-management abilities and adherence. Medical staff should provide personalized care according to the patient's self-management status and needs, promote the establishment of self-management behaviours and prevent and delay disease progression. IMPACT: This study helps assist medical staff in the early management of patients with DR and provides a reference for the construction of prevention programs for patients.

Clinical presentation of perineal endometriosis and prognostic nomogram after surgical resection.

BACKGROUND: This retrospective study evaluated the clinical features of perineal endometriosis (PEM) and established a prognostic nomogram for recurrence probability in patients treated with surgical resection. METHODS: This study enrolled 130 PEM patients who had received surgical treatment in Peking Union Medical College Hospital (PUMCH) between January 1992 and September 2020. We collected their clinical features and conducted outpatient or telephone follow-up. The predictive nomogram was constructed based on 104 patients who had completed follow-up by July 2021. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. Calculating the area under the curve (AUC) via risk scores of patients aimed to further access the predictive power of the model. In addition, the survival curve was depicted using Kaplan-Meier plot and compared by log-rank method. RESULTS: Most PEM patients had been symptomatic for 24-48 months before the lesion resection. With a median 99.00 (interquartile range: 47.25-137.50) months of postoperative observation, there were 16 (15.1%) out of 104 cases who finished follow-up reported symptomatic recurrence. On multivariate analysis of derivation cohort, multiple lesions, microscopically positive margin (mPM) and anal sphincter involvement (ASI) were selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.84 (95% CI 0.77-0.91). The calibration curve for probability of recurrence for 36, 60 and 120 months showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 36, 60 and 120 months were 0.89, 0.87 and 0.82 respectively. CONCLUSIONS: PEM is a rare kind of endometriosis and surgery is the primary treatment. Multiple lesions and ASI are independent risk factors for postoperative recurrence, and wide resection with more peripheral tissue could be preferred. The proposed nomogram resulted in effective prognostic prediction for PEM patients receiving surgical excision. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.

Oral gonadotropin-releasing hormone antagonists for treating endometriosis-associated pain: a systematic review and network meta-analysis.

OBJECTIVE: To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain. DESIGN: Systematic review and network meta-analysis. SETTING: Not applicable. PATIENT(S): Premenopausal women with endometriosis who had experienced moderate or severe pain. INTERVENTION(S): The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022. Only randomized controlled trials were included. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool 2. A Bayesian random-effects network meta-analysis was used to perform indirect comparisons. I2 was used to assess the global heterogeneity. Relative treatment estimates were performed. Treatment ranking was performed through the surface under the cumulative ranking curve. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. MAIN OUTCOME MEASURE(S): Endometriosis-associated pain, dysmenorrhea, dyspareunia, and noncyclic pelvic pain reduction. RESULT: (s): Five studies and 6 randomized controlled trials, including a total of 2,796 women and 10 different doses of oral GnRH antagonist treatments, were eligible for inclusion. All studies were considered to have a low risk of bias. Almost all efficacy- and safety-related outcomes showed a dose-response relationship. Regarding endometriosis-associated pain, the top 3 treatments were elagolix 400 mg, linzagolix 75 mg, and linzagolix 200 mg, with mean differences of -1.26 (95% credible interval [CrI], -1.70 to -0.79), -0.98 (95% CrI, -1.84 to -0.15), and -0.98 (95% CrI, -1.90 to -0.064), respectively. The top 3 treatments to decrease dysmenorrhea were relugolix 40 mg, elagolix 400 mg, and relugolix 20 mg, with mean differences of -1.60 (95% CrI, -2.07 to -1.14), -1.25 (95% CrI, -1.56 to -0.95), and -1.10 (95% CrI, -1.59 to -0.62), respectively. However, only high-dose treatments were significantly associated with most quality of life- and adverse effect-related outcomes. Relugolix 40 and 20 mg and elagolix 400 mg, with odds ratios of 6.88 (95% CrI, 2.18-24.58), 1.60 (95% CrI, 0.62-4.13), and 1.85 (95% CrI, 1.05-3.30), had a significantly increased incidence of adverse events. CONCLUSION: (s): Oral GnRH antagonists are effective for endometriosis-associated pain and dysmenorrhea and the patient global impression. The incidence of ovarian hypoestrogenic effects in a short-term duration was significant in a dose-effect response, particularly the highest dose. CLINICAL TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews registration number CRD42022332904.

Does Dysmenorrhea Affect Clinical Features and Long-Term Surgical Outcomes of Patients With Ovarian Endometriosis? A 12-Year Retrospective Observational Cohort Study.

Background: To examine and compare the differences in clinical characteristics and long-term postoperative outcomes of ovarian endometriomas (OMA) patients with and without dysmenorrhea, including data from at least 8 years of postoperative follow-up examinations. Methods: Retrospective analysis of 334 OMA patients, including their demographic and clinical data. Long-term follow-up record was also collected. All laparoscopic cystectomy procedures were performed by the same surgeon at Peking Union Medical College Hospital between January 2009 and April 2013. Patients were divided into the dysmenorrhea and non-dysmenorrhea groups to perform the analysis of their preoperative characteristics, relevant surgical findings, and postoperative outcomes at the follow-up. Results: Out of 334 OMA patients, 257 (76.9%) patients were allocated to the dysmenorrhea group, while the rest 77 (23.1%) patients were included in the non-dysmenorrhea group. Compared with the dysmenorrhea group, the non-dysmenorrhea group exhibited a reduced proportion of chronic pelvic pain (CPP) (P = 0.003), dyspareunia (P < 0.001), tenesmus (P < 0.001), concurrency of deep infiltrating endometriosis (DIE) (P < 0.001), and adenomyosis (P = 0.032). Preoperative infertility was significantly higher in the dysmenorrhea group (P = 0.001). The mean operating time in the dysmenorrhea vs. the non-dysmenorrhea group was 68.0 vs. 56.0 min (P < 0.001). According to the revised American Fertility Society (rAFS) scoring system, the mean scores of the two groups were 52.1 vs. 44.6 (P = 0.033). During follow-up, the dysmenorrhea group showed a higher rate of disease relapse (P < 0.001). A minimum postoperative follow-up period of 8 years was required to evaluate the pregnancy outcomes. Successful pregnancies were identified in 97/257 (37.7%) cases in the dysmenorrhea group and 36/77(46.8%) cases in the non-dysmenorrhea group (P = 0.157), respectively. Though the dysmenorrhea group had a higher rate of postoperative infertility, differences were not significant between the two groups. Conclusions: Compared with the dysmenorrhea group, OMA patients without dysmenorrhea exhibited lower proportions of CPP, dyspareunia, tenesmus, lower concurrency of DIE and adenomyosis, shorter mean operating time, lower mean rAFS scores, and lower infertility rates. During the long-term follow-up, a lower recurrence rate was observed in the non-dysmenorrhea group. Regarding fertility outcomes, non-dysmenorrhea patients had a higher likelihood of successful pregnancy after surgery. Postoperative management needs to be evaluated separately according to dysmenorrhea pathology.

The Development of Predictive Nomogram of Recurrence for Patients With Endometrioma After Cystectomy Who Were Younger Than 45 Years Old and Received Postoperative Therapy.

Objective: This study aimed to establish an effective prognostic nomogram for the postoperative recurrence of endometrioma or endometriosis-related pain for patients with endometrioma after long-term follow-up, who were younger than 45 years old and received postoperative therapy. Methods: The predictive nomogram was based on 323 patients who underwent cystectomy for endometrioma at Perking Union Medical College Hospital from January 2009 to April 2013, and the last follow-up occurred in September 2018. We collected information on all included patients, including preoperative data, intraoperative data, and long-term follow-up data after surgery. The Cox proportional hazards regression model was used to evaluate the prognostic effects of multiple clinical parameters on recurrence. The survival curve was depicted based on Kaplan-Meier method and compared by log-rank method. The Index of concordance (C-index) and calibration curves were used to access the discrimination ability and predictive accuracy of the nomogram respectively, and the results were further validated via bootstrap resampling. In addition, calculating the area under the curve (AUC) via risk scores of patients aimed to further access the prediction ability of the model. Results: On multivariate analysis of derivation cohort, independent factors for recurrence such as dysmenorrhea degree, sum of both cyst diameters, presence of adenomyosis, and other essential factors for recurrence such as age at surgery, presence of uterine fibroids were all selected into the nomogram. The C-index of the nomogram for predicting recurrence was 0.683 (95% CI, 0.610- 0.755). The calibration curve for probability of recurrence for 7 years and 9 years showed great agreement between prediction by nomogram and actual observation. Furthermore, the AUCs of risk score for 7-year and 9-year were 0.680 and 0.790 respectively. Conclusion: This research tried to develop the predictive nomogram of recurrence for patients with endometrioma after cystectomy. The C-index and calibration curve of nomogram, as well as the AUC of the nomogram was potential to predict the recurrence probability. In addition, this predictive nomogram needs external data sets to further validate its prognostic accuracy in the future.

Technique integration of single-cell RNA sequencing with spatially resolved transcriptomics in the tumor microenvironment.

BACKGROUND: The tumor microenvironment contributes to tumor initiation, growth, invasion, and metastasis. The tumor microenvironment is heterogeneous in cellular and acellular components, particularly structural features and their gene expression at the inter-and intra-tumor levels. MAIN TEXT: Single-cell RNA sequencing profiles single-cell transcriptomes to reveal cell proportions and trajectories while spatial information is lacking. Spatially resolved transcriptomics redeems this lack with limited coverage or depth of transcripts. Hence, the integration of single-cell RNA sequencing and spatial data makes the best use of their strengths, having insights into exploring diverse tissue architectures and interactions in a complicated network. We review applications of integrating the two methods, especially in cellular components in the tumor microenvironment, showing each role in cancer initiation and progression, which provides clinical relevance in prognosis, optimal treatment, and potential therapeutic targets. CONCLUSION: The integration of two approaches may break the bottlenecks in the spatial resolution of neighboring cell subpopulations in cancer, and help to describe the signaling circuitry about the intercommunication and its exact mechanisms in producing different types and malignant stages of tumors.