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.

Development and validation of a prediction model for postoperative urinary retention after prolapse surgery: A retrospective cohort study.

BACKGROUND: Postoperative urinary retention (POUR), a common condition after prolapse surgery with potential serious sequelae if left untreated, lacks a clearly established optimal timing for catheter removal. This study aimed to develop and validate a predictive model for postoperative urinary retention lasting > 2 and > 4 days after prolapse surgery. METHODS: We conducted a retrospective review of 1,122 patients undergoing prolapse surgery. The dataset was divided into training and testing cohorts. POUR was defined as the need for continuous intermittent catheterization resulting from a failed spontaneous voiding trial, with passing defined as two consecutive voids ≥ 150 mL and a postvoid residual urine volume ≤ 150 mL. We performed logistic regression and the predicted model was validated using both training and testing cohorts. RESULTS: Among patients, 31% and 12% experienced POUR lasting > 2 and > 4 days, respectively. Multivariable logistic model identified 6 predictors. For predicting POUR, internal validation using cross-validation approach showed good performance, with accuracy lasting > 2 (area under the curve [AUC] 0.73) and > 4 days (AUC 0.75). Split validation using pre-separated dataset also showed good performance, with accuracy lasting > 2 (AUC 0.73) and > 4 days (AUC 0.74). Calibration curves demonstrated that the model accurately predicted POUR lasting > 2 and > 4 days (from 0 to 80%). CONCLUSIONS: The proposed prediction model can assist clinicians in personalizing postoperative bladder care for patients undergoing prolapse surgery by providing accurate individual risk estimates.

The Diagnostic Accuracy of a Retrograde Voiding Trial for Restoration of Spontaneous Voiding Function after Prolapse and Urinary Incontinence Surgery.

STUDY OBJECTIVE: To assess the diagnostic accuracy of a retrograde voiding trial for the restoration of spontaneous voiding function after prolapse and urinary incontinence surgery and thereby determine whether the retrograde method can be a reliable alternative to the spontaneous voiding trial. DESIGN: A retrospective cohort study. SETTING: A single tertiary hospital in South Korea. PATIENTS: Women who underwent operations for prolapse, urinary incontinence, or both. INTERVENTION: Sequential voiding trials on postoperative day 1 or 2-retrograde voiding trial followed by spontaneous voiding trial. MEASUREMENTS AND MAIN RESULTS: Of the 408 women analyzed, 278 (68.1%) passed the spontaneous voiding trial on the first day of assessment and none experienced urinary retention after a successful voiding trial. Receiver operating characteristic analyses of retrograde voiding trials evaluating voided volume (VV), postvoid residual (PVR), and voiding efficiency (VE) all demonstrated high diagnostic accuracy for restoration of spontaneous voiding function, whereas measuring PVR and VE had better discriminative ability than VV (area under the curve [95% confidence interval] = 0.93 [0.90-0.95] for PVR, 0.94 [0.91-0.96] for VE, and 0.88 [0.85-0.91] for VV; DeLong's test between PVR/VE and VV p < .01). The optimal cutoffs determined by the Youden index were 200 mL for VV (sensitivity 85.0%, specificity 78.0%), 100 mL for PVR (sensitivity 84.0%, specificity 87.0%), and 66.7% for VE (sensitivity 86.0%, specificity 88.0%). CONCLUSIONS: The retrograde voiding trial is an accurate predictor for restoration of spontaneous voiding function after prolapse and incontinence surgery and can be a useful alternative to the spontaneous voiding trial.

TAZ/Wnt-ß-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2, leading to end-stage renal disease. The Hippo signaling pathway regulates organ growth and cell proliferation. Herein, we demonstrate the regulatory mechanism of cystogenesis in ADPKD by transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo signaling effector. TAZ was highly expressed around the renal cyst-lining epithelial cells of Pkd1-deficient mice. Loss of Taz in Pkd1-deficient mice reduced cyst formation. In wild type, TAZ interacted with PKD1, which inactivated ß-catenin. In contrast, in PKD1-deficient cells, TAZ interacted with AXIN1, thus increasing ß-catenin activity. Interaction of TAZ with AXIN1 in PKD1-deficient cells resulted in nuclear accumulation of TAZ together with ß-catenin, which up-regulated c-MYC expression. Our findings suggest that the PKD1-TAZ-Wnt-ß-catenin-c-MYC signaling axis plays a critical role in cystogenesis and might be a potential therapeutic target against ADPKD.

Development and validation of a prediction model for bothersome stress urinary incontinence after prolapse surgery: A retrospective cohort study.

OBJECTIVE: To develop and validate a prediction model for bothersome stress urinary incontinence after prolapse surgery and to compare it with an existing clinical prediction model (CUPIDO model). DESIGN: Retrospective cohort study. SETTING: Two tertiary hospitals in South Korea. POPULATION: A total of 1142 patients who underwent prolapse surgery with or without a concomitant midurethral sling. METHODS: To construct a prediction model, we performed logistic regression using both exhaustive and stepwise variable selection, validating the model both internally and externally. MAIN OUTCOME MEASURES: Bothersome stress urinary incontinence defined as the presence of bothersome symptoms of stress urinary incontinence and/or subsequent continence procedure one year after surgery. RESULTS: Postoperative bothersome stress urinary incontinence occurred in 10% of patients. A model containing six predictors (age, diabetes mellitus, subjective urinary incontinence, prolapse reduction stress test result, type of prolapse surgery, and a concomitant midurethral sling) showed excellent performance for predicting bothersome stress urinary incontinence (area under the curve 0.74, 95% confidence interval 0.62-0.86) and outperformed the CUPIDO model (area under the curve 0.63, 95% confidence interval 0.49-0.76; DeLong's test P = 0.014). CONCLUSIONS: This prediction model might be a useful tool to guide patient decision making regarding a concomitant continence procedure at the time of prolapse surgery. The predictive value of this model needs to be validated further in cohorts with different characteristics. TWEETABLE ABSTRACT: The proposed prediction model for bothersome stress urinary incontinence after prolapse surgery outperforms an existing model.

Posterior repair versus no posterior repair for posterior vaginal wall prolapse resolved under simulated apical support at the time of native tissue apical suspension.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the impact of an adjuvant posterior repair (PR) on treatment outcomes of native tissue apical suspension. MATERIALS AND METHODS: This retrospective cohort study included 194 women who underwent iliococcygeus or uterosacral ligament suspension with or without PR for Pelvic Organ Prolapse Quantification (POPQ) stage 2-4 posterior vaginal wall prolapse that resolved under simulated preoperative apical support and who completed a 1-year follow-up. The primary outcome was composite surgical failure defined as the presence of vaginal bulge symptoms, descent of the vaginal apex more than one-third of the way into the vaginal canal (apical recurrence), anterior or posterior vaginal wall descent beyond the hymen (anterior or posterior recurrence), or retreatment for prolapse. Secondary outcomes included anatomical outcomes, perioperative outcomes, obstructed defecation, dyspareunia, and adverse events. RESULTS: One hundred thirty women underwent concomitant PR, and 64 did not. Surgical failure rates were significantly higher in the group not receiving PR than in the group receiving PR (29.7% vs. 12.3%, p < 0.01). Anatomically, anterior and apical recurrence was more common in the group not receiving PR (p < 0.05). Concomitant PR was associated with a longer operating time and more blood loss (p < 0.01). However, there were few adverse events related to PR, and the rates of de novo obstructed defecation and dyspareunia were low in both groups, with no significant difference between the groups. CONCLUSION: Concomitant PR at the time of native tissue apical suspension may reduce the recurrence of symptomatic anterior and apical prolapse without significant morbidity.

Suture Complication Rates and Surgical Outcomes According to the Nonabsorbable Suture Materials Used in Vaginal Uterosacral Ligament Suspension: Polyester versus Polypropylene.

STUDY OBJECTIVE: To evaluate suture complication rates and surgical outcomes according to the nonabsorbable suture materials used in vaginal uterosacral ligament suspension (USLS) surgery. Multifilament polyester (polyethylene terephthalate [PET]) and monofilament polypropylene (PP) sutures were compared. DESIGN: Retrospective cohort study. SETTING: Single teaching hospital. PATIENTS: Total of 229 patients who underwent transvaginal USLS and completed a 1-year follow-up. INTERVENTIONS: Use of PET and PP sutures for transvaginal USLS procedures. MEASUREMENTS AND MAIN RESULTS: PP sutures were used in 149 patients, and PET sutures were used in 80 patients. The suture-related complication rates, including granulation tissue and suture erosion at the vaginal apex, were significantly higher in the PET suture group than in the PP suture group (46.3% vs 20.1%, p <.01). However, there was no significant difference in the rates of surgical failure (defined as the presence of vaginal bulging symptoms, apical descent ≥ half of the total vaginal length, anterior or posterior vaginal wall descent beyond the hymen, or retreatment for prolapse) between the 2 groups (p = .84). CONCLUSION: Compared with the use of multifilament PET sutures, the use of monofilament PP sutures in transvaginal USLS may reduce suture-related complications without increasing surgical failure rates.

Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease.

Altered miRNA (miR) expression occurs in various diseases. However, the therapeutic effect of miRNAs in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Genome-wide analyses of miRNA expression and DNA methylation status were conducted to identify crucial miRNAs in end-stage ADPKD. miR-192 and -194 levels were down-regulated with hypermethylation at these loci, mainly in the intermediate and late stages, not in the early stage, of cystogenesis, suggesting their potential impact on cyst expansion. Cyst expansion has been strongly associated with endothelial-mesenchymal transition (EMT). Zinc finger E-box-binding homeobox-2 and cadherin-2, which are involved in EMT, were directly regulated by miR-192 and -194. The therapeutic effect of miR-192 and -194 in vivo and in vitro were assessed. Restoring these miRs by injection of precursors influenced the reduced size of cysts in Pkd1 conditional knockout mice. miR-192 and -194 may act as potential therapeutic targets to control the expansion and progression of cysts in patients with ADPKD.-Kim, D. Y., Woo, Y. M., Lee, S., Oh, S., Shin, Y., Shin, J.-O., Park, E. Y., Ko, J. Y., Lee, E. J., Bok, J., Yoo, K. H., Park, J. H. Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease.

An autoregulatory enhancer controls mammary-specific STAT5 functions.

Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development and function. We report that the ubiquitously expressed Stat5a/b locus is subject to additional lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitivity, H3K27 acetylation and binding by GR, NFIB, ELF5 and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these sites in mice and determine their biological function. Mutant animals exhibited an 80% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that contributes to the remarkable abundance of STAT5 and, in turn, to the efficacy of STAT5-dependent mammary physiology.

Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes.

Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy of these loci by STAT5, EZH1 and RNA Pol II. Limited activation of differentiation-specific genes was observed in mammary epithelium lacking both EZH2 and STAT5, suggesting a modulating but not mandatory role for STAT5. Loss of EZH2 did not result in overt changes in genome-wide and gene-specific H3K27me3 profiles, suggesting compensation through enhanced EZH1 recruitment. Differentiated mammary epithelia did not form in the combined absence of EZH1 and EZH2. Transplantation experiments failed to demonstrate a role for EZH2 in the activity of mammary stem and progenitor cells. In summary, while EZH1 and EZH2 serve redundant functions in the establishment of H3K27me3 marks and the formation of mammary alveoli, the presence of EZH2 is required to control progressive differentiation of milk secreting epithelium during pregnancy.

Targeting the Epigenome as a Novel Therapeutic Approach for Breast Cancer.

Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to undergo hypermethylation at promoter region in breast cancer. In addition, histone deacetylases (HDACs) contribute to transcriptional repression by removing acetyl group at lysine residues leading to tumorigenesis. Since epigenetic changes are reversible, therapeutic approaches have been applied with epigenetic modification drugs such as DNMT inhibitors and HDAC inhibitors. In this chapter, we will summarize the feature of epigenetic markers in breast cancer cells and the effect of single or combination of epigenetic reagents for breast cancer therapy.

Type specimens of Heteroptera (Insecta: Hemiptera) collected from North Korea and adjacent regions deposited at Insect Collections of Chungnam National University (CNU) in Daejeon, Republic of Korea.

A list of type specimens of Heteroptera (Insecta: Hemiptera) collected from North Korea (mostly by the late Dr. Michail Josifov, Sofia, Bulgaria) acquired earlier by E. Heiss, now donated to and deposited in the insect collections of Chungnam National University (CNU), Deajeon, Korea, is presented. A total of 31 holotypes and 694 paratypes of 41 species and 1 subspecies in 6 families and 9 subfamilies are presented: Miridae (Deraeocorinae, Mirinae, Orthotylinae, Phylinae), Tingidae (Tinginae), Piesmatidae (Piesmatinae), Berytidae (Metacanthinae), Cymidae (Cyminae), Pentatomidae (Asopinae).

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.

Hypomethylation of ATP1A1 Is Associated with Poor Prognosis and Cancer Progression in Triple-Negative Breast Cancer.

Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. METHODS: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. RESULTS: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. CONCLUSION: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

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.

Anatomic Criterion for Clinically Relevant Apical Prolapse in Urogynecology Populations.

IMPORTANCE: Despite recognition of the critical role of the apex in vaginal support, there is no consensus on the anatomic criteria for clinically relevant apical prolapse. OBJECTIVE: The aim of this study was to define an optimal anatomic criterion for clinically relevant apical prolapse. STUDY DESIGN: This retrospective cohort study included 3,690 patients who had visited a tertiary hospital for ambulatory urogynecologic care. Vaginal bulge symptom was defined as a response of "somewhat," "moderately," or "quite a bit" to Question 3 on the Pelvic Floor Distress Inventory-20. Receiver operating characteristic curves were generated for a vaginal bulge symptom and apical support (Pelvic Organ Prolapse Quantification point C and C/total vaginal length [TVL]). RESULTS: Both point C and the C-to-TVL ratio (C/TVL) had excellent performance for predicting vaginal bulge symptoms (area under the curve, 0.917 and 0.927, respectively). The optimal cutoffs were -3.0 for C and -0.50 for C/TVL. When we analyzed the data set according to the TVL, there was a significant difference in the cutoffs for C, whereas those for C/TVL had little difference. There was no difference in the cutoffs of C and C/TVL according to hysterectomy status. CONCLUSIONS: The C/TVL is more appropriate than point C as a measure to define an anatomic criterion for clinically relevant apical prolapse. Descent of the vaginal apex beyond the halfway point of the vagina could be considered as an anatomic threshold for clinically relevant apical prolapse. This finding needs to be validated in nonurogynecology populations.

CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells.

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells.

How and on whom to perform uterine-preserving surgery for uterine prolapse.

The demand for uterine preservation in pelvic reconstructive surgery for uterovaginal prolapse is steadily increasing, and several procedures have been introduced, such as sacrospinous hysteropexy, uterosacral hysteropexy, sacrohysteropexy, and hysteropectopexy. However, the benefits and risks of uterine-preserving surgeries are not well understood. This review discusses the current evidence surrounding uterine-preserving surgery for uterovaginal prolapse repair. This may help surgeons and patients have a balanced discussion on how and on whom to perform uterine-preserving surgery.