Emission Wavelength-Tunable Bicyclic Dioxetane Chemiluminescent Probes for Precise In Vitro and In Vivo Imaging.

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of ß-Gal, H2O2, and superoxide with high specificity and a limit of detection of 77 mU L-1, 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of ß-Gal, H2O2, and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

A time-frame comparison study of surgical volume shifts on female primary stress urinary incontinence surgery.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the surgical volume shifts for primary female stress urinary incontinence (SUI) over a 20-year period (1999-2018) in Taiwan. METHODS: This was a retrospective cohort study based on Taiwan's National Health Insurance Research Database. We divided the time-frame into four periods: first period (1999-2003), second period (2004-2008), third period (2009-2013), and fourth period (2014-2018). The variables included major surgical types for SUI (retropubic urethropexy, pubovaginal sling, midurethral sling, etc.), surgeon gender, specialty, surgical volume (high ≥30, median 5-29, low <5), and hospital accreditation level. Reoperation rates within 1 year were analyzed as an outcome measurement. RESULTS: A total of 51,018 patients were identified. Major surgical types increased significantly during the first three periods and slightly decreased during the fourth period. The proportion of surgical volume shifted from high- to medium-, and low-volume, but it reversed during the fourth period. The proportion of SUI surgeries decreased in medical centers, whereas it increased in regional and local hospitals. The proportion of SUI surgeries by female surgeons increased. Similar phenomena occurred in MUS. As for surgeon specialty, major surgical types were performed by gynecologists and urologists equally, whereas MUS were performed more by gynecologists than by urologists. Unexpectedly, 1-year reoperation rates were higher in high-volume surgeons. CONCLUSIONS: The surgical trend of SUI surgeries shifted from high- to medium-, and low-volume surgeons, medical centers to regional and local hospitals during the study periods. This implied surgical skills and performance spreading, which may have a great influence on patient and healthcare provider choice of treatment.

Favorable cervical cancer mortality-to-incidence ratios of countries with good human development index rankings and high health expenditures.

BACKGROUND: Cervical cancer is highly preventable. The mortality-to-incidence ratio (MIR) is a marker that reflects the available screening interventions and clinical outcomes of cancer treatments. The association between the MIR for cervical cancer and cancer screening disparities among countries is an interesting issue but rarely investigated. The present study sought to understand the association between the cervical cancer MIR and the Human Development Index (HDI). METHODS: Cancer incidence and mortality rates were obtained from the GLOBOCAN database. The MIR was defined as the ratio of the crude mortality rate to the incidence rate. We used linear regression to analyze the correlation of MIRs with the HDI and current health expenditure (CHE) in 61 countries selected based on data quality. RESULTS: The results showed lower incidence and mortality rates and MIRs in more developed regions. In terms of regional categories, Africa had the highest incidence and mortality rates and MIRs. The incidence and mortality rates and MIRs were lowest in North America. Furthermore, favorable MIRs were correlated with a good HDI and high CHE as a percentage of gross domestic product (CHE/GDP) (both p < 0.0001). CONCLUSIONS: The MIR variation for cervical cancer is associated with the ranking of the health system and health expenditure, which further supports the role of cancer screening and treatment disparities in clinical outcomes. The promotion of cancer screening programs can reduce the cervical cancer global incidence and mortality rates and MIRs.

High-intensity focused ultrasound treatment for large and small solitary uterine fibroids.

This retrospective study used data from patients treated for uterine fibroids with ultrasound-guided high-intensity focused ultrasound (USgHIFU) from April 2015 to April 2019. One hundred and seven patients with solitary fibroids were divided into two groups: (1) the L group with larger fibroids (≥10 cm) and (2) the S group with smaller fibroids (<10 cm). Using magnetic resonance imaging (MRI), we examined the efficacy of high-intensity focused ultrasound (HIFU) ablation by comparing uterine and fibroid volumes before and three months after the procedure. The three-month follow-up clinical visit used a visual analog scale and a uterine fibroid symptom health-related quality of life questionnaire to evaluate clinical symptoms. Both the L and S groups had significant reduction in uterine and fibroid volumes, but the rate was significantly higher in the S group (p < 0.05). Both groups also had improvements in clinical symptoms, but there was no statistical difference. USgHIFU reduced the size of both large and small fibroids but was most effective on fibroids smaller than 10 cm. Both the L and S groups had improved dysmenorrhea symptoms and quality of life.

The Er:YAG vaginal laser for management of women with genitourinary syndrome of menopause (GSM).

The purpose of our study was to investigate the effects of vulvovaginal erbium laser on the genitourinary syndrome of menopause (GSM) and sexual function of postmenopausal women. We conducted a retrospective study of sixty-four postmenopausal women with GSM, and these patients were scheduled for three times of vulvovaginal erbium laser treatment. A baseline and post-treatment vaginal status was assessed by measuring vaginal pH, patients' subjective vulvovaginal atrophy (VVA) symptoms, which included dryness, dyspareunia, itching, and burning. The urinary response to treatment was assessed using ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6. Sexual function was evaluated using the Female Sexual Function Index (FSFI) before and after vulvovaginal laser therapy. Patient follow-ups were scheduled for 12 months after treatment. A total of sixty-four patients were enrolled in the study. We observed the significant improvement in the percentage of negative symptoms (dryness/dyspareunia/itching/burning) and in lower urinary tracts symptoms evaluated with ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6 (P < 0.05). Patients' overall satisfaction regarding their sexual life, assessed via Female Sexual Function Index (FSFI), showed significant improvement in its six domains of sexual function (P < 0.05). The pH level of vaginal secretions significantly decreased. No long-term complications were found post-treatment. The Er:YAG vaginal laser procedure is associated with a significant improvement in GSM and sexual function of postmenopausal women. Our result demonstrates that it can be a safe and efficacious treatment for patients with GSM without any serious adverse effects up to 1-year post-treatment. The long-term effects of using vulvovaginal laser in the treatment of GSM should be investigated.

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason's trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.

Regulating the Anticancer Efficacy of Sgc8-Combretastatin A4 Conjugates: A Case of Recognizing the Significance of Linker Chemistry for the Design of Aptamer-Based Targeted Drug Delivery Strategies.

The unique merits of aptamers, including specificity, high binding affinity, easy cell internalization, and rapid tissue accumulation abilities, have led aptamer-drug conjugates to evolve into one of the most attractive strategies for targeted drug delivery purposes. Nevertheless, the critical role of linkers in regulating anticancer efficacy of these conjugates, especially those engineered by automated modular synthesis techniques, has been rarely explored. In this work, we utilized Sgc8c aptamer and combretastatin A4 to develop three conjugates with either a phosphodiester bond linker, a disulfide bond linker, or a carbamate linker to study their payload release mechanisms and the influence on anticancer efficacy. These investigations allowed us to identify the unique activation pathway of the phosphodiester bond linker that is activated by both nucleophilic attack of glutathione and degradation caused by phosphodiesterase, which is highly associated with the higher cytotoxicity of the conjugate. Importantly, the understanding of the chemistry of phosphodiester bond linker activation allowed us to further design another XQ-2d-CA4 conjugate that can induce pancreatic cancer cells apoptosis in a more efficient manner.

Impact of COVID-19 on Pregnancy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19's during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age. Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.

Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

The effects of simulated childbirth trauma on the gene expression of neurotransmitter receptors in the bladder of female rats.

BACKGROUND/PURPOSE: To investigate the effects of simulated childbirth on the gene expression of parasympathetic muscarinic, purinergic (P2X), and neurokinin receptors of lower urinary tract in rats. METHODS: In all, twenty-four primiparous pregnant Sprague-Dawley female rats were equally divided into three groups: (1). Control group; 8 rats, (2) intra-vaginal balloon dilation for 2 h group; 8 rats, (3) and for 4 h group; 8 rats. After balloon dilatation for 4 months, all rats were sacrificed. We analyzed the gene expression of parasympathetic muscarinic, purinergic (P2X), and neurokinin receptors by real-time quantitative PCR (q-PCR). We quantified pro-inflammatory cytokines of TNF-α and IL-6 by Enzyme-linked immunosorbent assays (ELISA). The urodynamic parameters and micturition frequency by cystometry (CMG) were recorded. RESULTS: Our results showed that the balloon dilation significantly increased micturition frequency and modified peak micturition pressure compare to those in the control groups. Balloon dilation significantly decreased voiding interval and bladder volume compared to those in the control groups. Gene expressions of M3 muscarinic, P2X3 purinergic receptors, and significantly increased following balloon dilation for 2 hours and 4 hours than those in the control group. In addition, we found that NK1R and NK3R receptors were significantly decreased after balloon dilation compare to control group. The marked increase of TNF-α and IL-6 were also seen in the 2 balloon groups. CONCLUSION: The results of our study suggested that birth trauma may impair the function of urinary tract, this being partly related to the changes in the gene expression of the neurotransmitter receptors of the lower urinary tract.

Bladder Hyperactivity Induced by Oxidative Stress and Bladder Ischemia: A Review of Treatment Strategies with Antioxidants.

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague-Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks' LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Low Intensity Extracorporeal Shock Wave Therapy as a Novel Treatment for Stress Urinary Incontinence: A Randomized-Controlled Clinical Study.

Background and Objectives: To evaluate the effects of low intensity extracorporeal shock wave therapy (LiESWT) on stress urinary incontinence (SUI). Materials and Methods: This investigation was a multicenter, single-blind, randomized-controlled trial study. Sixty female SUI patients were randomly assigned to receive LiESWT with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/s, once weekly for a 4-week (W4) and 8-week (W8) period, or an identical sham LiESWT treatment without energy transmission. The primary endpoint was the changes in urine leakage as measured by a pad test and validated standardized questionnaires, while the secondary endpoint was the changes in a 3-day urinary diary among the baseline (W0), the W4 and W8 of LiESWT, and 1-month (F1), 3-month (F3), and 6-month (F6) follow-up after LiESWT. Results: The results showed that 4 weeks of LiESWT could significantly decrease urine leakage based on the pad test and validated standardized questionnaire scores, as compared to the sham group. Moreover, 8 weeks of LiESWT could significantly reduce urine leakage but increase urine volume and attenuate urgency symptoms, which showed meaningful and persistent improvement at W8, F1, F3, and F6. Furthermore, validated standardized questionnaire scores were significantly improved at W8, F1, F3, and F6 as compared to the baseline (W0). Conclusions: Eight weeks of LiESWT attenuated SUI symptoms upon physical activity, reduced urine leakage, and ameliorated overactive bladder symptoms, which implied that LiESWT significantly improved the quality of life. Our findings suggested that LiESWT could serve as a potentially novel and non-invasive treatment for SUI.

Time-frame comparison of hystero-preservation in the surgical treatment of uterine prolapse: a population-based nation-wide follow-up descriptive study, 2006-2013 versus 1997-2005.

INTRODUCTION AND HYPOTHESIS: The purpose of our study was to describe the surgical trend and time-frame comparison between 1997-2005 (1stperiod) and 2006-2013 (2nd period) of hystero-preservation for uterine prolapse, based upon a nationwide population-based National Health Insurance (NHI) claim data in Taiwan. METHODS: Women, who underwent primary surgeries for uterine prolapse, either uterine suspension with hystero-preservation or hysterectomy during 1997-2013, were identified from National Health Insurance Research Database (NHIRD).We analyzed the related variables including surgical types (hystero-preservation or hysterectomy), patient age and concomitant anti-incontinence surgery, surgeon age, gender, and service volume; and hospital accreditation level, and service volume. RESULTS: We identified a total of 46,968 inpatients, 6629 (14.11%) hystero-preservation group, and 40,339 (85.89%) hysterectomy group. Hystero-preservation significantly increased during the 17 year follow-up study period (1997 to 2013) (P value =0.0147). The overall surgeries for uterine prolapse increased among patients ≥70 years, with concomitant anti-incontinence surgery, surgeons ≥45 years, high volume surgeons, and hospitals. Multiple logistic regression revealed hysterectomy was less used in 2nd period (OR 0.45, 95%, confidence interval (CI) 0.43-0.48). Hysterectomy was more often used in patient aged ≥50 years, surgeon aged ≥45 years, and low volume hospitals. In case of concomitant anti-incontinence surgery (OR 0.48, CI 0.45-0.52), high volume surgeons (more than 30 surgeries) and hospitals (more than 73 surgeries) hystero-preservation was more often used. CONCLUSIONS: Time-frames, younger patients, concomitant anti-incontinence surgery, younger surgeons, and high volume surgeons and hospitals increase hystero-preservation for uterine prolapse. Surgeons and hospitals should be ready to respond to the wishes of female patients who want to preserve the uterus.

Surgical Trends and Time Frame Comparison of Surgical Types of Hysterectomy: A Nationwide, Population-based 15-year Study.

STUDY OBJECTIVE: To investigate the surgical trends among different types of hysterectomy (abdominal, vaginal, laparoscopic, and subtotal) over a 15-year period in Taiwan. DESIGN: A retrospective cohort study. SETTING: A population-based National Health Insurance Research Database. PATIENTS: Women undergoing various types of hysterectomy for noncancerous lesions. INTERVENTIONS: Data for this study were extracted from the inpatient expenditures by admissions files of Taiwan's National Health Insurance Research Database from 1998 through 2012 and divided into three 5-year time frames: first (1998-2002), second (2003-2007), and third (2008-2012). The variables included types of hysterectomy, patient age, gynecologist age and sex, hospital accreditation level, and surgical volume. Chi-square and trend tests were used to examine the association between the variables. MEASUREMENTS AND MAIN RESULTS: A total of 329 438 patients who underwent various types of hysterectomy were identified; 306 257 were included in the study. During the 15-year period, 45% underwent total abdominal hysterectomy, 41% underwent laparoscopic hysterectomy (LH), 9.8% underwent vaginal hysterectomy, and 4.2% underwent subtotal abdominal hysterectomy. The frequency of LHs increased from 35.9% in the first period to 43.9% in the second period and remained at 44.2% in the third period. During the same time period, there was a decrease in the frequency of total abdominal hysterectomies. Typically, younger patients underwent LHs by gynecologists with large volume surgical practices and medical centers. CONCLUSION: This 15-year study describes an increase of LHs and subtotal abdominal hysterectomies over time and provides evidence of surgical trends and a paradigm shift of hysterectomies. Surgical skills and performance extended from high- to low-surgical volume gynecologists and from medical centers to regional and local hospitals. This shift may have a great influence on patient and health care provider choice of treatment.

Clinical outcomes on tension-releasing suture appendage on single-incision sling devices for postoperative voiding dysfunction involving undue tape tension.

INTRODUCTION AND HYPOTHESIS: To determine the clinical outcomes of adding a tension-releasing suture (TRS) appendage for manipulation of over-tensioned single-incision slings (SIS) as a means to relieve postoperative voiding dysfunction. METHODS: A retrospective observational study conducted from January 2010 to July 2017. The records of patients with urodynamic stress incontinence (USI) without needing concurrent procedures who underwent anti-incontinence surgery using MiniArc, Solyx, and Ajust with voiding dysfunction were collated and analyzed. The primary outcome measure was the recovery of normal post-void residual urine (PVR) after TRS manipulation. The secondary outcome measures were the pain intensity noted during manipulation (quantified by visual analog scale) and the continence rate [assessed by (1) objective cure: 1-h pad test weight < 2 g and absence of USI; (2) subjective cure index score ≤ 1 on question 3 of the UDI-6: "Urine leakage related to physical activity, coughing, or sneezing?"]. RESULTS: There were 73 patients with high post-void residual (PVR) urine. The 42 (9.5%) patients with over-tensioned slings were managed with TRS manipulation while the 31 patients (7%) with high PVR and no sling over-tension were managed with intermittent catheterization. All patients in both groups regained normal PVR. The TRS-manipulated group demonstrated an objective cure rate of 92.9% (39/42) and subjective cure rate of 91% (38/42). Pain experienced during TRS manipulation was significantly higher with the Ajust system (p = 0.018). Three patients had persistence of USI, two with MiniArc and one with Solyx. CONCLUSIONS: The TRS manipulation is a well-tolerated procedure that can effectively relieve voiding dysfunction for over-tensioned SIS without affecting continence cure rates.

Risks of interstitial cystitis among patients with systemic lupus erythematosus: A population-based cohort study.

OBJECTIVE: To investigate whether the risk of interstitial cystitis increases among the patients with systemic lupus erythematosus. METHODS: This was a nationwide population-based cohort study. Data were obtained from the National Health Insurance Research Database in Taiwan. Women aged >18 years newly diagnosed as systemic lupus erythematosus during 2001-2008 were identified as the control group. The comparison included individuals randomly selected from the National Health Insurance Research Database in the year of 2000, by matching one systemic lupus erythematosus participant with eight non-systemic lupus erythematosus participants with sex and age. These participants were followed up until being diagnosed as interstitial cystitis, or the end of 2011. Women diagnosed with lupus cystitis were excluded from this study. RESULTS: This study included 7240 women with systemic lupus erythematosus and 57 920 women without systemic lupus erythematosus as controls. The incidence rate of interstitial cystitis was significantly higher in the systemic lupus erythematosus group, with an incidence rate ratio of 2.26 (95% confidence interval 1.57-3.27, P < 0.0001). After adjustment, the risk increased by 2.45-fold (adjusted hazard ratio 2.45, 95% confidence interval 1.57-3.27, P < 0.05). Age as a factor increases incidence rate ratios among all age groups, 2.12-, 3.32- and 4.65-fold. Age ≥45 years had an increased adjusted hazard ratio (2.07, 95% confidence interval 1.37-3.13, P < 0.05). Comorbidities, for example, hypertension, diabetes mellitus, dyslipidemia and renal disease, were insignificant. CONCLUSIONS: This is the first population-based cohort study showing a higher incidence of interstitial cystitis among patients with systemic lupus erythematosus. These findings support the concordance of interstitial cystitis with autoimmune diseases, and the temporal relationship to develop interstitial cystitis in patients with systemic lupus erythematosus.

KRAS mutation coupled with p53 loss is sufficient to induce ovarian carcinosarcomas in mice.

Ovarian carcinosarcoma cancer is the most lethal form of gynecological malignancy, but the pathogenesis and biological function for this ovarian cancer remain unknown. We establishment the transgenic mouse model of K-rasG12D p53loxP/loxP and found that K-ras mutation and p53 deletion within the ovarian surface epithelium gave rise to ovarian lesions with a hyperproliferation and endometrioid glandular morphology. Furthermore, double mutant ovaries formed ovarian carcinosarcomas that were high grade and poorly differentiated. Induction was widely metastatic and spread to abdominal organs including liver, spleen, and kidney at 4 wk. We also confirmed the role of K-rasG12D in ovarian cancer cell lines MCAS and PA-1 and showed that K-rasG12D overexpression strongly induced cell proliferation, migration, and invasion. The ovarian cancer model we developed recapitulates the specific tumor histomorphology and the probable mechanism of malignant transformation in endometriosis.