Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Production of Bioactive Porcine Lactoferrin through a Novel Glucose-Inducible Expression System in Pichia pastoris: Unveiling Antimicrobial and Anticancer Functionalities.

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (PG1) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number PG1-rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe3+) and exhibited growth inhibition against various pathogenic microbes (E. coli, S. aureus, and C. albicans) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications.

Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia.

Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (p < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.

Non-opioid recreational drug use and a prolonged HIV outbreak among men who have sex with men in Taiwan: An incident case-control study, 2006-2015.

BACKGROUND/PURPOSE: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. METHODS: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. RESULTS: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05). CONCLUSION: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk.

[Review of classical prescription Ganjiang Lingzhu Decoction].

Ganjiang Lingzhu Decoction is one of the first 100 classical prescriptions published by China in 2018. According to the published literature, it was found that there is no review on the history, evolution and research progress of this prescription. In order to reflect the history, modifications, quality control and clinical applications, this paper focuses on the origination, evolution, current development and modern studies of Ganjiang Lingzhu Decoction, in the hope of providing a reference for the heritage and innovation of other classical prescriptions.

The changes and the predictors of suicide ideation and suicide attempt among HIV-positive patients at 6-12 months post diagnosis: A longitudinal study.

AIMS: This study examined the changes and the predictors of suicide ideation/suicide attempt and the moderating effects of psychosocial factors on the suicide ideation/suicide attempts among human immunodeficiency virus (HIV)-positive patients at 6-12 months post-diagnosis. BACKGROUND: Suicide behaviours are prevalent among newly diagnosed HIV-positive patients, but the changes in suicide behaviours after diagnosis and the role of psychosocial factors in these behaviours are not well studied. DESIGN: This study used a prospective longitudinal design. METHODS: A total of 113 participants diagnosed as HIV-positive for 6-12 months were recruited from the outpatient department. Data were collected from June 2015 - October 2016. They were asked to complete Beck's Scale for Suicide Ideation, the Beck Depression Inventory-II, the Body Image Scale, the Meaning in Life Questionnaire and the Multidimensional Scale of Perceived Social Support at baseline, the third month and the sixth month. RESULTS: The results showed the high occurrence rates for suicide ideation ranging from 27.2%, 21.6%, and 25.8% and suicide attempt ranging from 14.7%, 8.6%, and 13.3% at the baseline, the third month and the sixth month, respectively. The education level, social support from family and depressive symptoms were the predictors of suicide ideation. The history of depression disorders, depressive symptoms and social support from friends significantly predicted suicide attempt. Meaning in life-presence moderated the relationship between depressive symptoms and suicide ideation. CONCLUSIONS: After diagnosed for 6-12 months, HIV-positive patients remain the high-risk group for suicide ideation and attempt. Suicide intervention targeting the risk and protective factors are required for HIV-positive patients.

K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer.

AU-rich element-binding proteins (ARE-BPs) offer post-transcriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3'-UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients. Furthermore, cigarette smoke, a leading risk factor for lung cancer, was also identified to be an important contributor to increased KSRP expression. Remarkably, silencing of KSRP decreased cell proliferation, reversed anchorage-independent growth, and reduced migration/invasion, suggesting an oncogenic role for KSRP in lung cancer. Finally, we provide mechanistic evidence that KSRP promotes the down-regulation of Spry4 by a previously unidentified mechanism, i.e. post-transcriptional mRNA regulation.

Prevalence and Predictors of Depression Among People Living With HIV/AIDS: A National Study.

BACKGROUND: Depression is prevalent among people living with HIV/AIDS (PLWHA), but there are few longitudinal studies investigating the prevalence of depression among HIV respondents in Taiwan. OBJECTIVES: This study examined the trend in the prevalence of depression and its main predictors among PLWHA in Taiwan. METHODS: This study analyzed the 2-million random-sample data set of the Taiwanese longitudinal health research database using data from 2000 to 2011and applied the Internal Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes for the detection of HIV infection and depression. Chi-square tests and logistic regression analyses were conducted to determine predictive factors for depression. RESULTS: A total of 769 PLWHA who met the criterion of HIV infection were extracted from the database. Of these respondents, 20.03% had a diagnosis of depression after their HIV-positive diagnosis. The annual prevalence of depression among the study respondents increased significantly from 1.95% in 2000 to 6.93% in 2011 according to time trend analysis (χ = 6.428, df =11, p = .03). Multivariate, logistic regression analysis indicated a history of drug abuse was the main predictor of a diagnosis of depression. DISCUSSION: The increasing trend in the prevalence of depression revealed an urgent need for the development of care programs for PLWHA with depression. Such programs should take into consideration a history of drug abuse as a strong risk factor for the development of depression.

[Exploring Suicide Ideation and Suicide Attempts Among HIV-Positive Patients During the First Six Months to One Year After Their Diagnosis].

BACKGROUND: HIV-positive patients are at high risk of suicide behaviors. Because most previous studies have investigated suicide behaviors among HIV-positive patients during their first six months of diagnosis only, there is a current lack of understanding of suicide behaviors among this group. PURPOSE: This study aimed at HIV-positive patients who had been diagnosed between six months and one year ago and examined their suicide ideation and suicide attempt profiles and the associated factors of suicide. METHODS: This study adopted a cross-sectional design. A total of 114 HIV-positive patients were interviewed in the HIV clinics of a medical center in Taipei City. Information collections included demographic and HIV-related data and measurements of suicide ideation, suicide attempt, depression, body image, meaning in life, and social support. Independent samples t tests, chi square tests, and logistic regressions were conducted to examine the associated factors and predictors of suicide ideation and suicide attempt. RESULTS: Slightly over one-quarter (27.2 %) of the participants reported suicide ideation and 14.0% reported attempting suicide in recent one week prior the study interview. Duration since being diagnosed HIV-positive, level of education, and history of depression were each associated with suicide ideation, while only history of depression was associated with suicide attempt. Having a higher level of education and having a higher level of social (family) support were both predictors of lower risk of suicide ideation, while having a higher level of depression predicted a greater risk of suicide attempt. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study found high prevalences of suicide ideation and attempting suicide among HIV-positive patients during the six month to one year period after diagnosis. Moreover, the prevalence was similar to that among HIV-positive patients during the first six months of diagnosis. Suicide prevention should be a focus of care plans provided to HIV-positive patients during their first year after diagnosis. These results may be provided as a reference for developing suicide-prevention strategies for HIV-positive patients. Routine screening for depression, guiding families to increase their provision of social support, and giving assistance to individuals with higher levels of depression contribute to the effective prevention of suicide among HIV-positive patients.

Long-term Durability of Responses to 2 or 3 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Adults on Antiretroviral Therapy.

Background: Previous studies have shown that the durability of serological response is impaired in successfully vaccinated human immunodeficiency virus-1 (HIV-1) positive subjects after receiving 2 doses of inactivated hepatitis A virus (HAV) vaccine. We evaluated whether 3 doses compared with 2 doses of HAV vaccine could improve the long-term seroprotection for this susceptible group. Methods: Antibody persistence among HIV-positive men who have sex with men aged 18-40 years who had received 2 or 3 doses of HAV vaccine according to a 0-6- or a 0-1-6-month schedule was evaluated biannually for 5 consecutive years in this prospective, nonrandomized cohort study. Results: At the end of 5 years, seroprotection persisted in 79% (146/185) versus 76% (85/110) and 94% (146/155) versus 88% (84/95) of the 3- versus 2-dose primary responders by intention-to-treat and per-protocol analyses, respectively (P > .05). Throughout the 5 years, the geometric mean concentrations of anti-HAV immunoglobulin G (IgG) were significantly higher for the 3-dose than the 2-dose group. In the multivariable analysis, a 3-dose regimen compared with a 2-dose regimen (odds ratio = 3.36; 95% confidence interval = 1.14-9.93) was independently associated with sustained seroprotection. Conclusions: Three doses versus 2 doses of HAV vaccine improve the durability of immune responses in terms of higher concentrations of specific IgG, which take longer to decay to subthreshold levels.

DFT-Supported Threshold Ionization Study of Chromium Biphenyl Complexes: Unveiling the Mechanisms of Substituent Influence on Redox Properties of Sandwich Compounds.

High-resolution mass-analyzed threshold ionization (MATI) spectra of (η6 -Ph2 )2 Cr and (η6 -Ph2 )(η6 -PhMe)Cr demonstrate that the Ph groups work as electron donors, decreasing the ionization energy of the gas-phase bisarene complexes. In contrast to electrochemical data, a close similarity of the Ph and Me group effects on the oxidation of free sandwich molecules has been revealed. However, DFT calculations testify for the opposite shifts of the electron density caused by the Me and Ph substituents in the neutral complexes, the latter behaving as an electron-accepting fragment. On the contrary, in the bisarene cations, the Ph group becomes a stronger donor than methyl. This change provides the similar substituent effects observed with the MATI experiment. On the other hand, the well-documented opposite influence of the Me and Ph fragments on the redox potential of the (η6 -arene)2 Cr+/0 couple in solution appears to be a result of solvation effects but not intramolecular interactions as shown for the first time in this work.

Case report: term birth after fertility-sparing treatments for stage IB1 small cell neuroendocrine carcinoma of the cervix.

BACKGROUND: Advances in cervical cancer management for childbearing women have led to less radical approaches. Use of fertility-sparing treatment to treat small cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive nature of the disease, even in early stage disease. CASE PRESENTATION: A 25-year-old nulligravida woman presented with malodorous vaginal discharge and was diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan showed no evidence of parametrial invasion or distant metastasis. Clinical staging allocated her to stage IB1 disease. She underwent radical abdominal trachelectomy for reproductive purpose. Preoperative and postoperative chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing hormone agonist were administered. She had a spontaneous, uneventful pregnancy and successfully delivered a term baby via cesarean section 7 years after treatment. CONCLUSION: To our knowledge, we describe the first success in offering a fertility-preserving multimodality strategy to present favorable oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I SCNEC. Individualized multimodality therapy may be utilized in specific patients with early-stage cervical cancer to preserve their fertility.

Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1).

γ-Catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays. Moreover, the affects of γ-catenin on cell migration were observed to be p53-dependent. Mechanistically, the anti-migratory effects seen via γ-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. Furthermore, the re-expression of γ-catenin sensitized NSCLC cells to c-MET inhibitor-mediated growth inhibition. Taken together, we identify γ-catenin as a novel regulator of HAI-1, which is a critical regulator of HGF/c-MET signaling. Therefore, targeting γ-catenin-mediated HAI-1 expression might be a useful strategy to sensitize NSCLC to c-MET inhibitors.

Transmitted drug resistance of HIV-1 strains among individuals attending voluntary counselling and testing in Taiwan.

BACKGROUND: Genotypic drug resistance testing for HIV-1 has been integrated into voluntary counselling and testing (VCT) programmes to investigate the trends of transmitted drug resistance (TDR), including integrase mutations, among individuals with recent or chronic HIV infections in Taiwan. METHODS: Between 2006 and 2014, 745 of 21 886 subjects (3.4%) tested HIV positive in the VCT service. The BED assay was used to identify recent HIV infections. Genotypic resistance mutations were interpreted using the WHO 2009 list. Integrase resistance mutations were analysed using the Stanford HIV Drug Resistance Database. RESULTS: Three-hundred-and-sixty (48.3%) patients were recently infected with HIV-1. Of 440 patients linked to HIV care with analysable reverse transcriptase and protease genes, 49 (11.1%) were infected with HIV-1 harbouring at least one resistance-associated mutation (RAM). The prevalence of TDR to NRTIs, NNRTIs and PIs was 4.1%, 6.4% and 2.3%, respectively. TDR prevalence did not change significantly during the study period. CD4 counts ≤500 cells/mm(3) and hepatitis B surface antigen positivity were independent factors associated with acquiring drug-resistant HIV. The prevalence of integrase mutations was 3.2%. Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected. We found no statistically significant difference between patients with chronic infection and those with recent infection in the prevalence of drug-resistant mutations to any of the four classes of antiretroviral agents. CONCLUSIONS: The prevalence of TDR of HIV-1 strains to available antiretroviral agents is moderately high, but transmission of HIV-1 with drug-resistant mutations remains stable in Taiwan.

Willingness of human immunodeficiency virus-positive patients to donate their organs for transplantation in Taiwan: a cross-sectional questionnaire survey.

BACKGROUND: With the introduction of combination antiretroviral therapy (cART) that has significantly improved survival, human immunodeficiency virus (HIV)-positive patients may be potential organ donors to HIV-positive recipients in a few countries. Organ shortage remains a challenge for organ transplantation in Taiwan, where organ donation by HIV-positive patients remains prohibited by law. METHODS: We assessed the willingness of organ donation (should they be pronounced brain dead, and the ban on HIV-positive organ donation be lifted) among HIV-positive patients who received regular HIV care at a university hospital in a cross-sectional survey between May and August 2015 with the use of an anonymous, self-administered questionnaire interview. RESULTS: Of the 1010 participants, 93.7% were receiving cART with the latest mean CD4 count and plasma HIV RNA load of 587 cells/mm3 and 2.73 log10 copies/mL, respectively. Overall, 71.9% were willing to donate organs. In multivariate analysis, factors associated with willingness to donate organs included college or graduate school diploma (odds ratio [OR] 1.571, 95% confidence interval [CI] 1.166-2.191), registered willingness to donate in the National Health Insurance system (OR 9.430, 95% CI 1.269-70.051), and knowledge of the information on HIV-positive deceased donors (HIVDD) (OR 1.673, 95% CI 1.073-2.608). CONCLUSIONS: We concluded that a significant proportion (71.9%) of HIV-positive Taiwanese patients were willing to donate their organs. The willingness was associated with a higher education level, prior registered willingness to donate organs, and awareness of HIVDD.

Risk factors for failure of repeat midurethral sling surgery for recurrent or persistent stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To study the outcomes following repeat midurethral sling (MUS) surgery in patients with persistent or recurrent stress urinary incontinence after failure of primary MUS surgery and risk factors for surgical failure. METHODS: The medical records of 24 patients who underwent repeat MUS surgery at a single tertiary center from January 2004 to February 2014 were reviewed. The types of MUS used for the repeat surgey were transobturator, retropubic and single incision slings. Objective cure was defined as no demonstrable involuntary leakage of urine during increased abdominal pressure in the absence of a detrusor contraction observed during filling cystometry, and subjective cure was defined as a negative response to Urogenital Distress Inventory six (UDI-6) question 3 during follow-up between 6 months and 1 year postoperatively. The change in the inclination angle between the urethra and pubic axis was measured with introital ultrasonography and the cotton swab test performed. RESULTS: The objective and subjective cure rates were 79.2 % and 75 %, respectively. There were no differences in demographics between the patients with failure of surgery and those with successful surgery. Significant independent risk factors for failure of repeat MUS surgery were a change in cotton swab angle at rest and straining of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), a change in inclination angle of <30° (OR 4.6, 95 % CI 2.5 - 7.9°), intrinsic sphincter deficiency (OR 3.4, 95 % CI 1.8 - 6.1) and a mean urethral closure pressure of <60 cm H2O (OR 2.9, 95 % CI 1.5 - 4.5). In one patient the bladder was perforated. CONCLUSIONS: Repeat MUS surgery is safe and has a good short-term success rate, both objectively and subjectively, with independent risk factors for failure related to bladder neck hypomobility and poor urethral function.

Five-year follow-up study of Monarc transobturator tape for surgical treatment of primary stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: We hypothesized that transobturator tape (TOT) is safe and efficacious for the treatment of urodynamic stress incontinence in the long term. METHODS: We conducted a prospective study of patients with confirmed urodynamic stress incontinence (USI) who underwent a MonarcTM TOT procedure in a tertiary center between February 2006 and March 2009 without other concurrent surgical procedures. Urodynamics were conducted at 1 and 3 years postoperatively. Subjective evaluation included Incontinence Impact Questionnaire (IIQ-7), Urinary Distress Inventory Questionnaire (UDI-6), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Objective cure was defined as no urinary leakage demonstrable on provocative filling cystometry and/ or 1-h pad test of <2 g. Subjective cure was based on a negative response to question 3 in UDI-6. Paired-samples t test, chi-square, and Fisher exact tests were applied; p < 0.05 was considered significant. The log-rank tests were used to compare event-free survival. RESULTS: Sixty patients were enrolled, and 56 were evaluated at 5 years postoperatively. The majority were middle aged, postmenopausal, and overweight. Mean operating time was 31.1 ± 8.9 min, intraoperative complications were minor, and median period of follow-up was 80.3 ± 9.6 months. At 5 years of follow-up, objective and subjective cure rates were 89.3 % and 87.5 %, respectively. No mesh-related complications were seen. One patient needed a repeat midurethral sling procedure, and one patient each had bladder and bowel cancer. CONCLUSION: Monarc TOT was safe and retained its high cure rate in the short- and long-term treatment of stress urinary incontinence.

Seeking new surgical predictors of mesh exposure after transvaginal mesh repair.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to explore new preventable risk factors for mesh exposure. METHODS: A retrospective review of 92 consecutive patients treated with transvaginal mesh (TVM) in the urogynecological unit of our university hospital. An analysis of perioperative predictors was conducted in patients after vaginal repairs using a type 1 mesh. Mesh complications were recorded according to International Urogynecological Association (IUGA) definitions. Mesh-exposure-free durations were calculated by using the Kaplan-Meier method and compared between different closure techniques using log-rank test. Hazard ratios (HR) of predictors for mesh exposure were estimated by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: The median surveillance interval was 24.1 months. Two late occurrences were found beyond 1 year post operation. No statistically significant correlation was observed between mesh exposure and concomitant hysterectomy. Exposure risks were significantly higher in patients with interrupted whole-layer closure in univariate analysis. In the multivariate analysis, hematoma [HR 5.42, 95 % confidence interval (CI) 1.26-23.35, P = 0.024), Prolift mesh (HR 5.52, 95 % CI 1.15-26.53, P = 0.033), and interrupted whole-layer closure (HR 7.02, 95 % CI 1.62-30.53, P = 0.009) were the strongest predictors of mesh exposure. CONCLUSION: Findings indicate the risks of mesh exposure and reoperation may be prevented by avoiding hematoma, large amount of mesh, or interrupted whole-layer closure in TVM surgeries. If these risk factors are prevented, hysterectomy may not be a relative contraindication for TVM use. We also provide evidence regarding mesh exposure and the necessity for more than 1 year of follow-up and preoperative counselling.

Predictors for persistent urodynamic stress incontinence following extensive pelvic reconstructive surgery with and without midurethral sling.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify the predictors for persistent urodynamic stress incontinence (P-USI) in women following extensive pelvic reconstructive surgery (PRS) with and without midurethral sling (MUS). MMETHODS: A total of 1,017 women who underwent pelvic organ prolapse (POP) surgery from January 2005 to December 2013 in our institutions were analyzed. We included 349 USI women who had extensive PRS for POP stage III or more of whom 209 underwent concomitant MUS. RESULTS: Of the women who underwent extensive PRS without MUS, 64.3 % (90/140) developed P-USI compared to only 10.5 % (22/209) of those who had concomitant MUS. Those with concomitant MUS and PRS alone were at higher risk of developing P-USI if they had overt USI [odds ratio (OR) 2.2, 95 % confidence interval (CI) 1.3-4.0, p = 0.014 and OR 4.7, 95 % CI 2.0-11.3, p < 0.001, respectively], maximum urethral closure pressure (MUCP) of < 60 cm H2O (OR 5.0, 95 % CI 3.0-8.1, p < 0.001 and OR 5.3, 95 % CI 2.7-10.4, p < 0.001, respectively), and functional urethral length (FUL) of < 2 cm (OR 5.4, 95 % CI 2.7-8.8, p < 0.001 and OR 3.9, 95 % CI 2.4-6.9, p < 0.001, respectively). Parity ≥ 6 (OR 3.9, 95 % CI 1.7-5.2, p < 0.001) and Prolift T (OR 3.1, 95 % CI 1.9-4, p < 0.001) posed a higher risk of P-USI in those with concomitant surgery. Perigee and Avaulta A seemed to be protective against P-USI in those without MUS. CONCLUSIONS: Overt USI with advanced POP together with low MUCP and FUL values have a higher risk of developing P-USI. Therefore, counseling these women is worthwhile while considering the type of mesh used.