Intraoperative Complications and Perioperative and Surgical Outcomes of Single-Port Robotics-Assisted Sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to assess intraoperative and postoperative complication rates, along with perioperative and surgical outcomes, following single-port robotics-assisted sacrocolpopexy. METHODS: This retrospective case series included 200 patients who underwent single-port robotics-assisted sacrocolpopexy to treat Pelvic Organ Prolapse Quantification (POPQ) stage 2-4 symptomatic prolapse between April 2020 and August 2023 by a single surgeon. Intraoperative and postoperative complications and perioperative outcomes were evaluated for all the patients, whereas surgical outcomes for 74 patients were assessed at 1-year follow-up. Surgical failure was defined as the presence of any of the following: the presence of vaginal bulging symptoms, any prolapse beyond the hymen, or retreatment for prolapse. RESULTS: During the study period, 200 single-port robotics-assisted sacrocolpopexies were performed. The median age and body mass index were 65.0 years and 24.6 kg/m2 respectively. Most patients had POPQ stage 3 or 4 prolapse and underwent concomitant total hysterectomy. The median total operation time was 212.0 min, and none of the patients required conversion to laparoscopy or laparotomy. The intraoperative cystotomy rate was 2.5%, and one patient had a blood transfusion owing to presacral vessel injury. Postoperative complications of mesh exposure and wound hernia were 0.5% and 2.0% respectively. At 1 year postoperatively, the rate of composite surgical failure was 9.5%, with a 5.4% anatomical recurrence rate. None of the patients experienced apical prolapse recurrence, and one received anterior colporrhaphy for anterior compartment prolapse recurrence. CONCLUSIONS: Single-port robotics-assisted sacrocolpopexy is safe and effective, with low complication rates and favorable perioperative and surgical outcomes.

Changes in anti-Müllerian hormone values for ovarian reserve after minimally invasive benign ovarian cystectomy: comparison of the Da Vinci robotic systems (Xi and SP) and the laparoscopic system.

To investigate the impact on the ovarian reserve after minimally invasive ovarian cystectomy using two platforms, the Da Vinci robotic system (Xi and SP) and the laparoscopic system. Patients underwent laparoscopic or Da Vinci robotic (Xi or SP) ovarian cystectomy for benign ovarian cysts between January 1, 2018, and December 31, 2022 at Guro Hospital, Korea University Medical center. We measured the change of AMH values (%) = [(postAMH - preAMH)] × 100/preAMH. No significant differences in preoperative age, cyst size, estimated blood loss during surgery, hemoglobin drop, length of hospital stay, adhesion detachment rate and cyst rupture rate were observed. However, the operative time was significantly shorter in the laparoscopic group than that in the robotic group (67.78 ± 30.58 min vs. 105.17 ± 38.87 min, p < 0.001) The mean preAMH and postAMH were significantly higher with the Da Vinci robotic group than with the laparoscopic group (preAMH: 5.89 ± 4.81 ng/mL vs. 4.01 ± 3.59 ng/mL, p = 0.02, postAMH: 4.36 ± 3.31 ng/mL vs. 3.08 ± 2.60 ng/mL, p = 0.02). However, the mean ΔAMH was not significantly different between two groups. ΔAMH also did not demonstrate significant differences among the three groups; laparoscopic, Xi and SP robotic. Even in the patient groups with preAMH < 2 and diagnosed with endometriosis, the ΔAMH did not show significant differences between the laparoscopic and robotic groups. The Da Vinci robotic system is no inferior to conventional laparoscopic systems in preserving ovarian function.

Cost-effectiveness of endovascular therapy for acute stroke with a large ischemic region in Japan: impact of the Alberta Stroke Program Early CT Score on cost-effectiveness.

BACKGROUND: Although randomized clinical trials (RCTs) demonstrated short-term benefits of endovascular therapy (EVT) for acute ischemic stroke (AIS) with a large ischemic region, little is known about the long-term cost-effectiveness or its difference by the extent of the ischemic areas. We aimed to assess the cost-effectiveness of EVT for AIS involving a large ischemic region from the perspective of Japanese health insurance payers, and analyze it using the Alberta Stroke Program Early CT Score (ASPECTS). METHODS: The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) was a RCT enrolling AIS patients with ASPECTS of 3-5 initially determined by the treating neurologist primarily using MRI. The hypothetical cohort and treatment efficacy were derived from the RESCUE-Japan LIMIT. Costs were calculated using the national health insurance tariff. We stratified the cohort into two subgroups based on ASPECTS of ≤3 and 4-5 as determined by the imaging committee, because heterogeneity was observed in treatment efficacy. EVT was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay of 5 000 000 Japanese yen (JPY)/quality-adjusted life year (QALY). RESULTS: EVT was cost-effective among the RESCUE-Japan LIMIT population (ICER 4 826 911 JPY/QALY). The ICER among those with ASPECTS of ≤3 and 4-5 was 19 396 253 and 561 582 JPY/QALY, respectively. CONCLUSION: EVT was cost-effective for patients with AIS involving a large ischemic region with ASPECTS of 3-5 initially determined by the treating neurologist in Japan. However, the ICER was over 5 000 000 JPY/QALY among those with an ASPECTS of ≤3 as determined by the imaging committee.

Outcomes of robotic sacrocolpopexy.

This review aimed to summarize the complications and surgical outcomes of robot-assisted sacrocolpopexy. Nineteen original articles on 1,440 robotic sacrocolpopexies were reviewed, and three systematic reviews and meta-analyses were summarized in terms of intraoperative, perioperative, postoperative, and/or surgical outcomes. Robotic sacrocolpopexy has demonstrated low overall complication rates and favorable surgical outcomes. Nevertheless, long-term follow-up outcomes regarding objective and/or subjective prolapse recurrence, reoperation rates, and mesh-related complications remain unclear. Further research is required to demonstrate whether the robotic approach for sacrocolpopexy is feasible or can become the modality of choice in the future when performing sacrocolpopexy.

Learning curves and perioperative outcomes of single-incision robotic sacrocolpopexy on two different da Vinci® surgical systems.

This study aimed to report a single surgeon's early experience and learning curves of single-incision robotic sacrocolpopexy on two different robotic surgical platforms, namely, the single-site approach on da Vinci Xi® and single-port approach on da Vinci SP® surgical systems. This retrospective study included 123 consecutive cases of robotic sacrocolpopexy performed between June 2017 and June 2021 for the patients with Pelvic Organ Prolapse Quantification stage 2-4 symptomatic prolapse. First consecutive 57 cases were performed under the da Vinci Xi® system applying the single-site manner, whereas the following 66 cases were done under the da Vinci SP® system. The primary outcome was intraoperative and perioperative complication rates, and the secondary outcome was learning curve of single-incision robotic sacrocolpopexy under the two different robotic surgical platforms. Learning curves based on the operation time were obtained through cumulative sum analysis. The mean age of each group was 65.6 ± 8.7 years for single-site robotic sacrocolpopexy and 63.7 ± 7.6 years for the single-port one (p = 0.202). More than 80% of patients for each group had advanced prolapse stages and underwent concomitant total hysterectomy. The overall baseline characteristics did not differ significantly between groups. The median operation time for each group were 201.0 and 201.5 min, respectively. Both groups showed comparable perioperative outcomes in terms of operation time, intraoperative blood loss, and length of hospital stay. Intraoperative cystostomy rates were 1.8% and 3.0%, respectively, and revealed no statistical difference (p = 0.736). The learning curves were comparable, and the surgeon required less than 15 cases for both single-site and single-port robotic sacrocolpopexies to stabilize operation time. Comparable learning curves and favorable intraoperative and perioperative outcomes of single-incision robotic sacrocolpopexy using two different robotic surgical systems show that both are feasible options for robotic sacrocolpopexy.

LuxR-Type SCO6993 Negatively Regulates Antibiotic Production at the Transcriptional Stage by Binding to Promoters of Pathway-Specific Regulatory Genes in Streptomyces coelicolor.

SCO6993 (606 amino acids) in Streptomyces coelicolor belongs to the large ATP-binding regulators of the LuxR family regulators having one DNA-binding motif. Our previous findings predicted that SCO6993 may suppress the production of pigmented antibiotics, actinorhodin, and undecylprodigiosin, in S. coelicolor, resulting in the characterization of its properties at the molecular level. SCO6993-disruptant, S. coelicolor ΔSCO6993 produced excess pigments in R2YE plates as early as the third day of culture and showed 9.0-fold and 1.8-fold increased production of actinorhodin and undecylprodigiosin in R2YE broth, respectively, compared with that by the wild strain and S. coelicolor ΔSCO6993/SCO6993+. Real-time polymerase chain reaction analysis showed that the transcription of actA and actII-ORF4 in the actinorhodin biosynthetic gene cluster and that of redD and redQ in the undecylprodigiosin biosynthetic gene cluster were significantly increased by SCO6993-disruptant. Electrophoretic mobility shift assay and DNase footprinting analysis confirmed that SCO6993 protein could bind only to the promoters of pathway-specific transcriptional activator genes, actII-ORF4 and redD, and a specific palindromic sequence is essential for SCO6993 binding. Moreover, SCO6993 bound to two palindromic sequences on its promoter region. These results indicate that SCO6993 suppresses the expression of other biosynthetic genes in the cluster by repressing the transcription of actII-ORF4 and redD and consequently negatively regulating antibiotic production.

Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6d/d mice revert to their normal expression in Mig-6d/dErbb2d/d mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.

Artificial intelligence approaches to the determinants of women's vaginal dryness using general hospital data.

The aim of this study is to analyse the determinants of women's vaginal dryness using machine learning. Data came from Korea University Anam Hospital in Seoul, Republic of Korea, with 3298 women, aged 40-80 years, who attended their general health check from January 2010 to December 2012. Five machine learning methods were applied and compared for the prediction of vaginal dryness, measured by a Menopause Rating Scale. Random forest variable importance, a performance gap between a complete model and a model excluding a certain variable, was adopted for identifying major determinants of vaginal dryness. In terms of the mean squared error, the random forest (1.0597) was much better than linear regression (17.9043) and artificial neural networks with one, two and three hidden layers (1.7452, 1.7148 and 1.7736, respectively). Based on random forest variable importance, the top-10 determinants of vaginal dryness were menopause age, age, menopause, height, thyroid stimulating hormone, neutrophils, years since menopause, lymphocytes, alkaline phosphatase and blood urea nitrogen. In addition, its top-20 determinants were peak expiratory flow rate, low-density lipoprotein cholesterol, white blood cells, monocytes, cancer antigen 19-9, creatinine, eosinophils, total cholesterol, triglyceride and amylase. Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause, the thyroid function and systematic inflammation.Impact StatementWhat is already known on this subject? Only a few studies have investigated the risk factors of vaginal dryness in middle-aged women. More research is to be done for finding its various risk factors, identifying its major risk groups and drawing its effective clinical implications.What do the results of this study add? This study is the first machine-learning study to predict women's vaginal dryness and analyse their determinants. The random forest could discuss which factors are more important for the prediction of vaginal dryness. Based on random forest variable importance, menopause age was the most important determinant of vaginal dryness and their association was discovered to be negative in this study. Vaginal dryness was closely associated with the height, rather than the body weight or body mass index. The importance rankings of blood conditions related to systematic inflammation were within the top-20 in this study: neutrophils, lymphocytes, white blood cells, monocytes and eosinophils.What are the implications of these findings for clinical practice and/or further research? Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause and systematic inflammation.

Machine Learning Approaches to Identify Factors Associated with Women's Vasomotor Symptoms Using General Hospital Data.

BACKGROUND: To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. METHODS: Data on 3,298 women, aged 40-80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. RESULTS: In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. CONCLUSION: Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.

Surgical volume reduction and the announcement of triage during the 1st wave of the COVID-19 pandemic in Japan: a cohort study using an interrupted time series analysis.

PURPOSE: The coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for surgical staffs to minimize exposure to COVID-19 or save medical resources without harmful patient outcomes, in accordance with the statement of each surgical society. No research has empirically validated declines in surgical volume in Japan, based on the usage of surgical triage. We aimed to identify whether the announcement of surgical priorities by each Japanese surgical society may have affected the surgical volume decline during the 1st wave of this pandemic. METHODS: We extracted 490,719 available cases of patients aged > 15 years who underwent elective major surgeries between July 1, 2018, and June 30, 2020. After the categorization of surgical specialities, we calculated descriptive statistics to compare the year-over-year trend and conducted an interrupted time series analysis to validate the decline of each surgical procedure. RESULTS: Monthly surgical cases of eight surgical specialities, especially ophthalmology and ear/nose/throat surgeries, decreased from April 2020 and reached a minimum in May 2020. An interrupted time series analysis showed no significant trends in oncological and critical surgeries. CONCLUSION: Non-critical surgeries showed obvious and statistically significant declines in case volume during the 1st wave of the COVID-19 pandemic according to the statement of each surgical society in Japan.

Risk of type 2 diabetes is increased in nonobese women with polycystic ovary syndrome: the National Health Insurance Service-National Sample Cohort Study.

OBJECTIVE: To investigate the relationship between polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) in Korean women. DESIGN: Longitudinal case-control study. SETTING: Not applicable. PATIENT(S): PCOS patients aged 15 to 44 years (n = 1,136) and control individuals (n = 5,675), matched 1:5 by age group, income, and region of residence. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The occurrence of T2DM. RESULT(S): In the PCOS and control groups, 15.7% and 14.4%, respectively, were obese (body mass index ≥25 kg/m2). The incidence rate of T2DM was 15.84/1,000 and 5.80/1,000 person-years in the PCOS and control groups, respectively. The unadjusted hazard ratio (HR) of T2DM in women with PCOS was 2.6-fold higher than that in control individuals. Women with PCOS still had a higher HR of T2DM than did control individuals after adjustment for body mass index, family history of T2DM, physical exercise level, and total cholesterol. PCOS was significantly associated with T2DM in women both with and without obesity. CONCLUSION(S): PCOS is independently associated with an increased incidence of T2DM in both obese and nonobese women. Screening for T2DM should be considered for both obese and nonobese women with PCOS in Korea.

ß-catenin activates TGF-ß-induced epithelial-mesenchymal transition in adenomyosis.

Adenomyosis is defined as the presence of ectopic nests of endometrial glands and stroma within the myometrium. Adenomyosis is a common cause of dysmenorrhea, menorrhagia, and chronic pelvic pain but is often underdiagnosed. Despite its prevalence and severity of symptoms, its pathogenesis and etiology are poorly understood. Our previous study showed that aberrant activation of ß-catenin results in adenomyosis through epithelial-mesenchymal transition. Using transcriptomic and ChIP-seq analysis, we identified activation of TGF-ß signaling in the uteri of mutant mice that expressed dominant stabilized ß-catenin in the uterus. There was a strong positive correlation between ß-catenin and TGF-ß2 proteins in women with adenomyosis. Furthermore, treatment with pirfenidone, a TGF-ß inhibitor, increased E-cadherin expression and reduced cell invasiveness in Ishikawa cells with nuclear ß-catenin. Our results suggest that ß-catenin activates TGF-ß-induced epithelial-mesenchymal transition in adenomyosis. This finding describes the molecular pathogenesis of adenomyosis and the use of TGF-ß as a potential therapeutic target for adenomyosis.

A New Thermo-Responsive Hyaluronic Acid Sol-Gel to Prevent Intrauterine Adhesions after Hysteroscopic Surgery: A Randomized, Non-Inferiority Trial.

PURPOSE: To investigate the efficacy and safety of a newly developed thermo-responsive sol-gel, ABT13107, for reducing the formation of intrauterine adhesions (IUAs) after hysteroscopic surgery. MATERIALS AND METHODS: In this multicenter, prospective, randomized trial (Canadian Task Force classification I), 192 women scheduled to undergo a hysteroscopic surgery at one of the eight university hospitals in South Korea were randomized into the ABT13107 group or the comparator (Hyalobarrier®) group in a 1:1 ratio. During hysteroscopic surgery, ABT13107 or Hyalobarrier® was injected to sufficiently cover the entire intrauterine cavity. RESULTS: The patients returned to their respective sites for safety assessments at postoperative weeks 1 and 4 and for efficacy assessments at postoperative week 4. The post-surgery incidence of IUAs was 23.4% in the ABT13107 group and 25.8% in the comparator group; this difference met the criteria for ABT13107 to be considered as not inferior to the comparator. No differences were found in the extent of adhesions, types of adhesions, or the cumulative American Fertility Society score between the two treatment groups. Most adverse events were mild in severity, and no serious adverse events occurred. CONCLUSION: ABT13107, a new anti-adhesive barrier containing hyaluronic acid, was not inferior to the highly viscous hyaluronic acid anti-adhesive barrier, Hyalurobarrier® in IUA formation after hysteroscopic surgery (Clinical trial registration No. NCT04007211).

Efficacy and Safety of Cystatin C-Guided Renal Dose Adjustment of Cefepime Treatment in Hospitalized Patients with Pneumonia.

Cystatin C (CysC) may estimate renal function more accurately than serum creatinine (SCr). The clinical impact of renal dose adjustment of cefepime according to CysC rather than SCr has remained uncertain. We investigated the efficacy and safety of CysC-guided cefepime dosing compared with SCr-guided dosing in hospitalized patients with pneumonia. All adults hospitalized with pneumonia between July 2016 and December 2018 who used cefepime for at least 3 days were enrolled. Mortality, acute kidney injury (AKI), cefepime-induced encephalopathy (CIE), and Clostridium difficile infection were compared between the CysC-guided and SCr-guided groups. One hundred and ninety patients were divided into two groups: 129 and 61 received cefepime based on CysC and SCr, respectively. In-hospital mortality did not significantly differ between the groups (12% versus 31%; hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.31-1.77; p = 0.50). CysC-guided cefepime dosing decreased the risk of AKI (13% versus 61%; HR 0.18; 95% CI, 0.07-0.44; p < 0.001) and CIE (2% versus 11%; HR 0.11; 95% CI, 0.03-0.47; p = 0.003) compared with SCr-guided dosing. There was no significant difference in the risk of Clostridium difficile infection. CysC-guided dosing of cefepime was associated with decreased risk of the cefepime-associated morbidities including AKI and CIE without increasing mortality among the hospitalized patients with pneumonia.

Non-absorbable versus absorbable sutures for anterior colporrhaphy: study protocol for a randomised controlled trial in South Korea.

INTRODUCTION: The anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures. METHODS AND ANALYSIS: This is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03736811.

Identification of Serum Biomarkers for Diagnosis of Endometriosis Using Multiplex Immunoassays.

Endometriosis is a common gynecologic disorder characterized by chronic pelvic pain, dysmenorrhea, and infertility. Although this condition places significant financial burden on the healthcare system and negatively affects patient's quality of life, the pathophysiology of the disease remains unclear, and noninvasive diagnostic methods are insufficient. The object of this study was to identify potential biomarkers for endometriosis from peripheral blood. We hypothesized that serum biomarkers modified in endometriosis patients would be detected by multiplex cytokine panel, and identification of a combination of these biomarkers would improve diagnostic power. A total of 141 women, aged 15-52 years with regular menstruation, participated in this study. Twenty-one serum cytokines were detected using the commercially available MILLIPLEX MAP Human Cytokine/Chemokine Kit Panel IV. Among these cytokines, breast- and kidney-expressed chemokine (BRAK)/chemokine (C-X-C motif) ligand 14 (CXCL14) was significantly decreased, and proliferation-inducing ligand (APRIL)/tumor necrosis factor ligand superfamily member 13 (TNFSF13) was significantly increased in endometriosis group. APRIL/TNFSF13 and BRAK/CXCL14 alone or in combination, however, failed to show adequate sensitivity or specificity for the diagnosis of endometriosis. Combination of APRIL/TNFSF13 and BRAK/CXCL14 with serum CA-125 levels yielded significantly higher sensitivity (71.2%) for detecting endometriosis without compromising specificity (80.8%) than CA-125 alone in a logistic regression model (P = 0.050). In conclusion, we identified a biomarker combination that detects endometriosis better than CA125 alone. Therefore, we conclude that multiplex cytokine panel is an efficient method for detecting endometriosis, and analysis of additional cytokine panels may lead to identification of a novel biomarker combination with superior diagnostic power.

Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?

In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects.

Effects of preoperative oral management by dentists on postoperative outcomes following esophagectomy: Multilevel propensity score matching and weighting analyses using the Japanese inpatient database.

The purpose of this study was to investigate the effects of preoperative oral management (POM) by dentists on the incidence of postoperative pulmonary complications (PPCs), length of hospital stay, medical costs, and days of antibiotics administration following both open and thoracoscopic esophagectomy.Dental plaque is an established risk factor for postoperative pneumonia, which could be reduced by POM. However, few clinical guidelines for cancer treatment, including those for esophageal cancer, recommend POM as routine perioperative care.We extracted data of esophagectomy cases from the Japanese Diagnosis Procedure Combination database. We subsequently conducted propensity score (PS) analyses for multilevel data, including matching, inverse probability of treatment weighting (IPTW), and standardized mortality ratio weighting (SMRW), to estimate the effect of POM by dentists on the outcomes of esophagectomy.We analyzed 3412 esophagectomy cases of which 812 were open, and 2600 were thoracoscopic surgery. In IPTW analysis to estimate the average treatment effect, the risk difference of postoperative aspiration pneumonia ranged from -2.49% to -2.02% between the POM and control groups of both open and thoracoscopic esophagectomy cases. IPTW analyses indicated that the total medical costs of thoracoscopic esophagectomy were reduced by 221,200 to 253,100 Japanese Yen (equivalent to about $2000-$2200). In PS matching and SMRW analyses to estimate average treatment effect on treated, there was no difference in outcomes between the POM and control groups.Our results suggested that in patients undergoing open or thoracoscopic esophagectomy, POM by dentists prevented the occurrence of postoperative aspiration pneumonia. It could also reduce the total medical costs of thoracoscopic esophagectomy. Thus, POM by dentists can be considered as a routine perioperative care for all patients undergoing esophagectomy, regardless of the expected risk for PPC.

Loss of HDAC3 results in nonreceptive endometrium and female infertility.

Endometriosis is a disease in which tissue that normally grows inside the uterus grows outside the uterus and causes chronic pelvic pain and infertility. However, the exact mechanisms of the pathogenesis of endometriosis-associated infertility are unknown. Epigenetic dysregulation has recently been implicated in infertility. Here, we report a reduction of histone deacetylase 3 (HDAC3) protein amounts in eutopic endometrium of infertile women with endometriosis compared to a control group. To investigate the effect of HDAC3 loss in the uterus, we generated mice with conditional ablation of Hdac3 in progesterone receptor (PGR)-positive cells (Pgrcre/+Hdac3f/f ; Hdac3d/d ). Loss of Hdac3 in the uterus of mice results in infertility due to implantation failure and decidualization defect. Expression microarray and ChIP-seq analyses identified COL1A1 and COL1A2 as direct targets of HDAC3 in both mice and humans. Reduction of HDAC3 abrogated decidualization in a primary culture of human endometrial stromal cells (hESCs) similar to that observed in infertile patients with endometriosis. Whereas attenuation of HDAC3 resulted in p300 recruitment to Col1a1 and Col1a2 genes in the uterus of mice as well as hESCs, inhibition of p300 permitted hESCs to undergo decidualization. Collectively, we found attenuation of HDAC3 and overexpression of collagen type I in the eutopic endometrium of infertile patients with endometriosis. HDAC3 loss caused a defect of decidualization through the aberrant transcriptional activation of Col1a1 and Col1a2 genes in mice and COL1A1 and COL1A2 genes in humans. Our results suggest that HDAC3 is critical for endometrial receptivity and decidualization.