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.

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.

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.

Anterograde lag screw placement in the posterior column of the acetabulum: A case report and literature review.

Acetabular fractures are complex injuries with an annual incidence of approximately 4 per 100,000 (Laird and Keating, 2005 [1]. Although the open reduction is currently advocated for treating acetabular fractures, some acetabular fractures can be treated by minimally invasive surgery, with the advantages of minor trauma, less bleeding, reduced infection, and shorter operation time. Therefore, we report a case of a patient with a transverse fracture involving the acetabulum treated with a new method of cannulated screw fixation combined with a personalized 3D printed guide to achieving minimally invasive and precise treatment of acetabular fractures while we review the relevant papers.

PD-L1 cellular nanovesicles carrying rapamycin inhibit alloimmune responses in transplantation.

Organ transplantation has been employed upon serious injuries, but a T-cell-mediated potent inflammatory immune response often leads to graft rejection. Immunosuppressive drugs such as rapamycin (RAPA) have to be taken after organ transplantation, but long-term use of these drugs causes severe adverse effects. Immune checkpoint pathways such as the programmed death-receptor 1/programmed death-ligand 1 (PD-1/PD-L1) provides an immunosuppressive environment, preventing excessive tissue destruction due to inflammatory immune responses. In this study, we bioengineered cell membrane-derived PD-L1 nanovesicles (PD-L1 NVs) to carry low doses of RAPA. These NVs inhibited T-cell activation and proliferation in vitro, by enhancing the PD-1/PD-L1 immune co-inhibitory signaling axis and inhibiting the mTOR pathway. Importantly, PD-L1 NVs encapsulated with rapamycin exerted stronger effects on inhibiting T-cell proliferation than PD-L1 NVs or rapamycin alone. This can be recapitulated in a mouse skin transplantation model, leading to the weakened alloimmune response and allograft tolerance. We also found that PD-L1/rapamycin vesicles have additional function to induce regulatory T cells in the recipient spleens. Our study highlighted the power of combining low-dose rapamycin and PD-L1 in the nanovesicles as immunosuppressants to promote allograft acceptance.

CAB39 Promotes the Proliferation of Nasopharyngeal Carcinoma CNE-1 Cells via Up-Regulating p-JNK.

AIM: To investigate the role of CAB39 in nasopharyngeal carcinoma (NPC) development and examine its expression level in NPC tumor samples. METHODS: Immunohistochemistry staining of NPC tissue microarray was conducted to detect the expression of CAB39 protein in NPC tissues, and the clinical significance of CAB39 was evaluated. Lentivirus-mediated over-expression of CAB39 was designed to increase CAB39 expression in CNE-1 cells. Cell colony formation, cell cycle and CCK-8 proliferation experiments were performed to compare the proliferation ability of CNE-1 cells with or without CAB39 over-expression. Western blotting was conducted to examine downstream targets of CAB39. RESULTS: CAB39 expression was higher in tumor samples compared to normal tissue and the higher CAB39 expression was positively correlated to higher TNM stage and distant metastasis rate and non-keratinized state. Further, CAB39 over-expression dramatically increased the proliferation and colony formation of CNE-1 cells. Finally, higher p-JNK protein level was found in CAB39 over-expressing cells. CONCLUSION: CAB39 promotes the proliferation of CNE-1 cells via up-regulating p-JNK.

Efficacy and Side Effects of Drugs Commonly Used for the Treatment of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common benign disease of the prostate gland and is caused by benign hyperplasia of the smooth muscle cells and stromal cells in this important gland. BPH is also the most common disease underlying lower urinary tract symptoms (LUTS). The incidence of BPH increases with age and affects more than half of all men 50 years or older. BPH mainly exerts effects on urinary function and can seriously reduce a patient's quality of life. At present, treatment for BPH aims primarily to improve the quality of life and reduce the risk of BPH-related complications. Pharmacological therapy is recommended for moderate-to-severe cases of LUTS that are suggestive of BPH. A range of drugs is currently available to treat this condition, including α1-adrenoceptor antagonists, 5α-reductase inhibitors (5-ARIs), phosphodiesterase type 5 inhibitors (PDE5Is), muscarinic receptor antagonists (MRAs), ß3-adrenoceptor agonists, and plant extracts. Of these, the most commonly used drugs in the clinic are α1-adrenoceptor antagonists, 5-ARIs, and combination therapy. However, these drugs exert their effects via various mechanisms and are associated with adverse reactions. The purpose of this review is to provide current comprehensive perspectives on the mechanisms of action, efficacy, and adverse reactions associated with the drugs most commonly used for the treatment of BPH.