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.

Decreased Human Platelet Activation and Mouse Pulmonary Thrombosis by Rutaecarpine and Comparison of the Relative Effectiveness with BAY11-7082: Crucial Signals of p38-NF-κB.

Platelets play a critical role in arterial thrombosis. Rutaecarpine (RUT) was purified from Tetradium ruticarpum, a well-known Chinese medicine. This study examined the relative activity of RUT with NF-κB inhibitors in human platelets. BAY11-7082 (an inhibitor of IκB kinase [IKK]), Ro106-9920 (an inhibitor of proteasomes), and RUT concentration-dependently (1-6 µM) inhibited platelet aggregation and P-selectin expression. RUT was found to have a similar effect to that of BAY11-7082; however, it exhibits more effectiveness than Ro106-9920. RUT suppresses the NF-κB pathway as it inhibits IKK, IκBα, and p65 phosphorylation and reverses IκBα degradation in activated platelets. This study also investigated the role of p38 and NF-κB in cell signaling events and found that SB203580 (an inhibitor of p38) markedly reduced p38, IKK, and p65 phosphorylation and reversed IκBα degradation as well as p65 activation in a confocal microscope, whereas BAY11-7082 had no effects in p38 phosphorylation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay shows that RUT and BAY11-7082 did not exhibit free radical scavenging activity. In the in vivo study, compared with BAY11-7082, RUT more effectively reduced mortality in adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism without affecting the bleeding time. In conclusion, a distinctive pathway of p38-mediated NF-κB activation may involve RUT-mediated antiplatelet activation, and RUT could act as a strong prophylactic or therapeutic drug for cardiovascular diseases.

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.

Outcomes and failure risks in mid-urethral sling insertion in elderly and old age with urodynamic stress incontinence.

INTRODUCTION AND HYPOTHESIS: To study the surgical outcomes and risk factors for failure of three types of mid urethral slings(MUS) surgeries in elderly and old age women with urodynamic stress incontinence(USI). METHODS: Three different types of MUS surgeries [single incision sling(SIS), trans-obturator tape(TOT), retro-public mid-urethral sling-tension-free vagina tape (TVT)]were performed among three age groups of women (young <64 yr, elderly 65-74 yr and old >75 yr) with USI. They were followed up for 1 year. RESULTS: Complete postoperative data was available for 688 women. After 1 year, overall objective cure rate was 88.2% and subjective cure rate was 85.9%. Among the young, elderly, and old age women objective cure rates were 91.0%, 80.6%, 66.7% and subjective cure rates were 89.2%, 77.6%, 58.3% respectively. Urodynamic parameters demonstrated flow rate, higher post-void bladder residual, smaller cystometric capacity, and lower maximum urethral closure pressure were significantly lower among old and elderly group. Subjectively, urinary distress inventory-6 (UDI-6) and incontinence impact questionnaire-7(IIQ-7) improved significantly in all groups with significant changes from baseline only in older women. Intrinsic sphincter deficiency(ISD) was found to be significantly associated with failure in older women. Other preoperative comorbidities were equally distributed among all the three age groups. The operative time, perioperative complications, and length of hospital stay showed no difference between the study groups. CONCLUSIONS: MUS surgery is safe for the young and aging patients with USI and demostrated significant improvement in its outcomes, but objective and subjective cure rates decreases with age. ISD was also found to be significantly associated with failure.

Outcomes of urodynamic mixed urinary incontinence and urodynamic stress incontinence with urgency after mid-urethral sling surgery.

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI) is defined as symptomatic complaint of involuntary leakage associated with urgency and also with exertion, effort, sneezing or coughing. The paucity of research, especially on the surgical management of MUI, limits its best management. METHODS: This is a retrospective study to determine the outcomes of mixed urinary incontinence after mid-urethral sling surgery with two groups, urodynamic stress incontinence (USI) with urgency and urodynamic mixed urinary incontinence (MUI-UD; USI and detrusor overactivity [DO]). RESULTS: Ninety women (USI + urgency group) with preoperative USI and urgency and no demonstrable DO/DOI attained an objective cure of 82.2%, whereas the remaining 67 (MUI-UD group) women with both USI and DO/DOI were reported to have an objective cure of only 55.2%. Subjective cures were 81.1% and 53.7% respectively. The type of incontinence surgery does not affect postoperative outcomes in either of the groups. Demographic factors identified to have a significant negative effect on cure rates were postmenopausal status (p = 0.005), prior hysterectomy (p = 0.028), pre-operative smaller blafdder capacity (p = 0.001), and a larger volume of pre-operative pad test (p = 0.028). A lower mid-urethral closure pressure (MUCP) was significant with post-operative failure of treatment with MUI-UD group (68.8 ± 36.2 cmH2O vs 51.9 ± 24.7 cmH2O; p = 0.033). CONCLUSIONS: Although there is evidence for a good cure of the stress component of MUI, urodynamic investigation with its findings prior to management of MUI could have greater implications for selective patient centered counseling. Presence of DO or DOI on urodynamics resulted in poorer objective and subjective outcomes.

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.

Satisfaction in parturients receiving epidural analgesia after prenatal shared decision-making intervention: a prospective, before-and-after cohort study.

BACKGROUND: The explanation of epidural analgesia by anesthesiologist would often begin after the parturient is admitted to the hospital. Because of labor pain, the decision of receiving epidural analgesia would often be made by the family members, instead of the parturient herself. We aimed to test whether earlier prenatal shared decision-making (SDM) interventions increase parturient's comprehension and satisfaction of epidural labor analgesia, compared to conventional explanation after labor pain begun. METHODS: During the 28th week of gestation, we provided the SDM parturient health education as well as a leaflet with quick response codes. Scanning the code would link to education videoclips which explained what epidural analgesia is and its advantages and disadvantages. Original routine practice group parturients received explanation of analgesia after admission for delivery. To measure the satisfaction of labor pain service, the accessibility of information, and the communication with medical staff, we designed a questionnaire with reference to (1) Pregnancy and Maternity Care Patients' Experiences Questionnaire (PreMaPEQ), (2) Preterm Birth Experience and Satisfaction Scale (P-BESS), and (3) Women's Views of Birth Labor Satisfaction Questionnaire (WOMBLSQ). The questionnaire was amended after a pretest involving 30 parturients who had received epidural analgesia. Scree test analysis and exploratory factor analysis were performed; then, the questionnaire was revised again. A total of 200 valid questionnaires were collected-100 each from the original routine practice group and the SDM group. RESULTS: The SDM group reported significantly higher satisfaction with and understanding of epidural analgesia, and a significantly higher satisfaction with the information received, and the quality of pain relief. After SDM intervention, significant increasement of the average satisfaction scores in question "my epidural is effective" (9.10%; mean difference: 0.38; 95% confidence interval, 0.17 ~ 0.59; p < 0.001) and "The effect of epidural is just as what I have expected" (10.41%; mean difference: 0.41; 95% confidence interval, 0.18 ~ 0.64; p < 0.001) was demonstrated. CONCLUSIONS: An earlier prenatal SDM intervention with sufficient information through videoclips increased parturients' comprehensions and satisfaction of epidural analgesia service. TRIAL REGISTRATION: ISRCTN registry, 14,256,563. Registered April 1st, 2020 ( https://doi.org/10.1186/ISRCTN14256563 ).

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.

Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway.

Platelets are major players in the occurrence of cardiovascular diseases. Auraptene is the most abundant coumarin derivative from plants, and it has been demonstrated to possess a potent capacity to inhibit platelet activation. Although platelets are anucleated cells, they also express the transcription factor, nuclear factor-κB (NF-κB), that may exert non-genomic functions in platelet activation. In the current study, we further investigated the inhibitory roles of auraptene in NF-κB-mediated signal events in platelets. MG-132 (an inhibitor of proteasome) and BAY11-7082 (an inhibitor of IκB kinase; IKK), obviously inhibited platelet aggregation; however, BAY11-7082 exhibited more potent activity than MG-132 in this reaction. The existence of NF-κB (p65) in platelets was observed by confocal microscopy, and auraptene attenuated NF-κB activation such as IκBα and p65 phosphorylation and reversed IκBα degradation in collagen-activated platelets. To investigate cellular signaling events between PLCγ2-PKC and NF-κB, we found that BAY11-7082 abolished PLCγ2-PKC activation; nevertheless, neither U73122 nor Ro31-8220 had effect on NF-κB activation. Furthermore, both auraptene and BAY11-7082 significantly diminished HO• formation in activated platelets. For in vivo study, auraptene prolonged the occlusion time of platelet plug in mice. In conclusion, we propose a novel inhibitory pathway of NF-κB-mediated PLCγ2-PKC activation by auraptene in human platelets, and further supported that auraptene possesses potent activity for thromboembolic diseases.

Prophylactic midurethral sling insertion during transvaginal pelvic reconstructive surgery for advanced prolapse patients with high-risk predictors of postoperative de novo stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the clinical outcome of continent women with high-risk predictors for de novo stress urinary incontinence (SUI) offered prophylactic midurethral sling (MUS) insertion during vaginal pelvic reconstructive surgery (PRS) for advanced pelvic organ prolapse (POP). MATERIALS AND METHODS: This was a prospective cohort study in patients with POP stage ≥ 3 and maximum urethral closure pressure (MUCP) <60 cmH2O and functional urethral length (FUL) <2 cm. Patients were divided into PRS and PRS + MUS groups. Surgery commenced with vaginal hysterectomy, application of Uphold® and insertion of MUS to the PRS + MUS group. Main outcome measures were incidence of de novo urodynamic stress incontinence (USI), lower urinary tract symptoms (LUTS), quality of life (QoL), and topographic and anatomical relationship of implanted mesh. RESULTS: Based on sample size calculation, 40 patients were recruited-20 in each group. Rate of de novo USI in PRS + MUS was 5% objectively and 10% subjectively, while in the PRS it was 50% objectively and 60% subjectively. No significant difference was noted in patient demographics. Intraoperative blood loss was greater for PRS + MUS but was not statistically significant. No organ injuries, mesh exposure, or infections occurred. Postoperatively, MUCP significantly increased from 43.3 ± 8.9 to 58.5 ± 19.2 cmH2O and FUL from 17.2 ± 1.9 to 20.3 ± 3.1 mm in the PRS + MUS group. Residual urine significantly decreased. No patient had bladder outlet obstruction (BOO). Sonographic assessment showed no difference in mesh mobility with urethral kinking observed in 11 (55%) patients with MUS. CONCLUSION: Based on a validated small sample, prophylactic MUS for continent women at high risk for postoperative USI with advanced POP lowers its incidence to 5%. Continence is achieved in 95%. Concern for complications, LUTS, and QoL did not significantly differ.

Cumulative use of therapeutic bladder anticholinergics and the risk of dementia in patients with lower urinary tract symptoms: a nationwide 12-year cohort study.

BACKGROUND: Studies have shown an association between lower urinary tract symptoms (LUTS) and an increased risk of dementia. Whether anticholinergic use contributes to the development of dementia in patients with LUTS remains unknown, especially in Asian populations. This study aims to investigate the association between anticholinergic use and dementia in patients with LUTS. METHODS: This study included patients aged 50 years and over with newly diagnosed LUTS (January 2001 to December 2005), divided into four groups according to their cumulative defined daily doses (cDDDs) of anticholinergics: < 28 cDDDs, 28-84 cDDDs, 85-336 cDDDs, ≥337 cDDDs. Patients were followed up until dementia developed or until the end of 2012. RESULTS: We recruited a total of 16,412 patients. The incidence of dementia was 10% in the < 28 cDDD group, 8.9% in the 28-84 cDDD group, 11.5% in the 85-336 cDDD group, and 14.4% in the ≥337 cDDD group (p = .005). In a Cox proportional hazards analysis, the adjusted hazard ratio of dementia was 1.15 (95% CI = 0.97-1.37) in the 85-336 cDDD group, and 1.40 (95% CI = 1.12-1.75) in the ≥337 cDDD group after adjusting for covariates. CONCLUSIONS: Our study indicates that higher cumulative anticholinergic exposure is associated with an increase in the risk of incident dementia in patients with LUTS aged 50 years of age and over. Either using one anticholinergic agent or switching anticholinergic agents cumulatively increases this risk. Therapeutic risks and benefits of using anticholinergics in LUTS treatment should be clinically reviewed and weighed.

Evaluation of Clinical Outcome and Risk Factors for Failure of Single-incision Midurethral Short Tape Procedure (Solyx Tape) for Stress Urinary Incontinence.

STUDY OBJECTIVE: To evaluate the clinical outcome and identify risk factors for failure of the Solyx (Boston Scientific Corporation, Marlborough, MA) single-incision sling (SIS) in the treatment of urodynamic stress incontinence (USI). DESIGN: A retrospective observational study (Canadian Task Force classification II-2). SETTING: A tertiary referral center. PATIENTS: Patients diagnosed with USI without needing concurrent procedures that underwent continence surgery using the Solyx SIS from February 2015 to May 2017. INTERVENTIONS: Anti-incontinence surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was the rate of objective cure defined as the absence of demonstrable leakage of urine on the cough stress test and a 1-hour pad test weight of less than 2g. The secondary outcome was the rate of subjective cure defined as a negative response to Urinary Distress Inventory question 3 (no leakage on coughing, sneezing, or laughing) and the identification of the different risk factors of cure failure. A total of 113 patients were evaluated in the study. Postoperative USI and the 1-hour pad test significantly improved from 24.2 ± 26.9 gm (range, 19.1-29.3) to 2.5 ± 8.7 gm (range, 0.9-4.2); p <0.001 through 1 year. Data analysis showed an objective cure rate of 90% (102/113) and a subjective cure rate of 86% (97/113). USI recurred in 11 patients with no repeat surgery done becausesymptoms were tolerable to the patients. No patient had bladder outlet obstruction. Peak flow rates 23.7 ± 9.1 ml/s (20.0-27.4) and residual urine volume 38.5 ± 25.8 ml (29.8-47.2) were within normal limits with no significant changes. Previous anti-incontinent surgery, previous prolapsed surgery, intrinsic sphincter deficiency, maximum urethral closure pressure <40cm H2O, and neurogenic disease were significant risk factors for sling failure. Subjective assessment on the quality of life significantly improved (p <0.001). CONCLUSION: The Solyx SIS is an effective and safe treatment option for women with USI, showing high objective and subjective cure rates with a low incidence of complications 1 year after treatment. The identified independent risk factors forfailure are related to poor urethral function and previous pelvic reconstructive surgery.

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.

Pregnancy outcomes following nonobstetric surgery during gestation: a nationwide population-based case-control study in Taiwan.

BACKGROUND: Whether nonobstetric surgery during gestation is associated with a higher risk of spontaneous abortion or adverse delivery outcomes is still unclear. METHODS: We performed a retrospective case-control study using a Longitudinal Health Insurance Database (LHID 2000) containing claim-data of 1 million randomly selected beneficiaries. We compared the incidences and estimated the adjusted odds ratios (aOR) with 95% confidence interval (95% CI) for spontaneous abortion, adverse delivery outcomes, cesarean delivery, and prolonged hospital stay to determine the risk of adverse outcomes in women who had nonobstetric surgery during gestation as compared to those who did not have any surgery during gestation. RESULTS: After exclusion, we were left with 114,852 delivery and 3999 abortion cases in our study; and 462 (0.39%) of them had nonobstetric surgery under general or regional anesthesia during pregnancy. The leading surgeries were repair of cervical os (33.12%), appendectomy (17.32%), ovarian surgeries (13.64%), and fixation of fractured bone (8.01%).The risk of spontaneous abortion (4.23% vs. 2.43%, aOR:1.53; 95% CI: 1.01-2.31), antepartum hemorrhage (7.14% vs. 2.83%, aOR: 2.51; 95% CI: 1.74-3.61), pre-eclampsia/eclampsia (2.60% vs. 1.01%, aOR: 2.35; 95% CI: 1.30-4.23), gestational diabetes (2.38% vs. 0.69%, aOR: 3.12; 95% CI: 1.69-5.78), prematurity (9.06 vs. 4.90%, aOR: 3.31; 95% CI: 2.54-4.31), cesarean section (43.55% vs. 33.76%, aOR: 1.41; 95% CI: 1.17-1.71), and prolonged hospital stay (1.82% vs. 5.91%, aOR: 3.23; 95% CI: 2.16-4.83) were higher in those women who had nonobstetric surgery after adjusting for age and comorbidities. CONCLUSIONS: Nonobstetric surgery during gestation were associated with a higher risk of spontaneous abortion, adverse delivery outcomes, cesarean section, and prolonged hospital stay.

Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate.

Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2⁻PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.

Epidemiological profile and obstetric outcomes of patients with peripartum congestive heart failure in Taiwan: a retrospective nationwide study.

BACKGROUND: During pregnancy, the hyperdynamic physiology of circulation can exacerbate many cardiovascular disorders. Congestive heart failure (CHF) usually occurs during late pregnancy, which is significantly associated with a high level of maternal and neonatal morbidities and mortalities. The profile of women who develop peripartum CHF (PCHF) is unknown. We investigated the epidemiological profiles of PCHF. METHODS: In this retrospective cohort study, PCHF patients were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in Taiwan's National Health Insurance Research Database. Risk factors and obstetric outcomes were compared in women with and without PCHF. RESULTS: From 2,115,873 birth-mothers in Taiwan between 1997 and 2013, we identified 512 with PCHF (incidence: 24.20/105). More women with than without PCHF were older (≥ 35, 18.16% vs. 9.62%), and had more multifetal gestations (7.42% vs. 1.40%), gestational hypertension (HTN) (19.2% vs. 1.31%), and gestational diabetes mellitus (4.10% vs. 0.67%). After the analysis had been adjusted for confounders, the leading comorbidities associated with PCHF were structural heart diseases (adjusted odds ratio [aOR]: 67.21; 95% confidence interval [CI]: 54.29-83.22), pulmonary diseases (aOR: 13.12; 95% CI: 10.28-16.75), chronic HTN (aOR: 11.27; 95% CI: 6.94-18.28), thyroid disease (aOR: 9.53; 95% CI: 5.27-17.23), and gestational HTN (aOR: 5.16; 95% CI: 3.89-6.85). PCHF patients also had a higher rate of cesarean sections (66.41% vs. 34.46%; p < 0.0001). CONCLUSION: Maternal structural heart diseases, pulmonary diseases, thyroid disorders, and preexisting or gestational HTN are associated with a higher risk of developing PCHF. Birth-mothers with PCHF also had a higher risk of caesarean section and adverse outcomes, including maternal death. Our findings should benefit healthcare providers, and government and health insurance policy makers.

Novel synthetic benzimidazole-derived oligosaccharide, M3BIM, prevents ex vivo platelet aggregation and in vivo thromboembolism.

BACKGROUND: Thrombus formation, a phenomenon primarily related to increased platelet activation, plays a key role in cardiovascular and cerebrovascular diseases. Although the established antiplatelet agents, such as aspirin and clopidogrel, have been shown to be beneficial in treating thromboembolic diseases, they have considerable limitations. Hence, the development of more effective and safe antithrombotic agents is necessary to satisfy a substantial unmet clinical need. In recent years, the favorable properties of imidazole-related drugs have prompted medicinal chemists to synthesize numerous novel therapeutic agents. The chemical structure of the benzimidazole backbone has proven antiplatelet properties. Moreover, synthetic oligosaccharides have exhibited antiplatelet properties. Therefore, we developed a new aldo-benzimidazole-derived oligosaccharide compound, M3BIM, for achieving a stronger antiplatelet effect than the drugs which are being used in clinical aspects. We investigated the effects of M3BIM on platelet activation ex vivo and its antithrombotic activity in vivo. RESULTS: M3BIM (10-50 µM) exhibited a more potent activity in inhibiting platelet aggregation stimulated by collagen than it did in inhibiting that stimulated by thrombin in washed human platelets. The M3BIM treatment revealed no cytotoxicity in zebrafish embryos, even at the highest concentration of 100 µM. In addition, M3BIM inhibited the phosphorylation of phospholipase Cγ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 2 and c-Jun N-terminal kinase 1), and markedly reduced the ATP-release reaction and intracellular calcium mobilization in collagen-activated platelets. By contrast, M3BIM showed no effects on either collagen-induced p38 MAPK and Akt phosphorylation or phorbol 12, 13-dibutyrate-induced PKC activation and platelet aggregation. Moreover, the M3BIM treatment substantially prolonged the closure time in human whole blood, and increased the occlusion time in mesenteric microvessels and attenuated cerebral infarction in mice. For the study of anticoagulant activities, M3BIM showed no significant effects in the prolongation of activated partial thromboplastin time and prothrombin time in mice. CONCLUSION: The findings of our study suggest that M3BIM is a potential therapeutic agent for preventing or treating thromboembolic disorders.

Trends in reoperation for female stress urinary incontinence: A nationwide study.

AIMS: Using the National Health Insurance (NHI) database in Taiwan, the study aimed to evaluate the rates and associated factors for reoperation of female stress incontinence. METHODS: Records of female patients who had received a primary surgical treatment for stress incontinence from January 2000 to December 2006 were retrieved. Among these, patients who had reoperations during follow-up till December 2010 were identified. The data were analyzed for reoperation rates, surgery methods, patient demography, surgeon, and hospital attributes. RESULTS: Among 14,613 patients with a mean follow-up of 86.28 ± 26.76 months, 563 (3.85%) had reoperations, an incidence rate of 54.37 per 10,000 person year (PY). Injection procedures had the highest reoperation rate of 893.30/10,000 PY. The adjusted hazard ratio (HR) of reoperation was higher for mid-urethral sling when compared to pubovaginal sling (HR 1.54, 95% CI 1.16-2.05) or retropubic urethropexy including Burch operation (HR 1.30, 95% CI 1.04-1.61). Surgeons with high service volumes tended to have fewer reoperations. No correlations were noted between the reoperation rate with patient age, surgeon age/gender, year of operation and hospital status. However, urologists had higher reoperation rates than gynecologists. For repeat surgery, the majority of patients chose the same specialty but different surgical types. Mid-urethral sling was used most commonly in 48.85% of reoperations. CONCLUSIONS: Substantial number of patients need reoperation for stress incontinence. The choice of primary surgery type and surgeon specialty may affect the reoperation rates. Mid-urethral sling is the most common reoperation choice.

Evaluation of the single-incision Elevate system to treat pelvic organ prolapse: follow-up from 15 to 45 months.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the 2-year clinical outcomes of pelvic reconstructive surgery with the single-incision Elevate system (American Medical Systems, Minnetonka, MN, USA). METHODS: This retrospective study was conducted from November 2010 to August 2013, and included 210 patients with pelvic organ prolapse stage 3 or 4 who underwent pelvic reconstructive surgery with an Elevate system and were followed for 1 to 3 years postoperatively. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and multi-channel urodynamic examinations. Anatomical success was defined as postoperative POP-Q stage 0 or I. RESULTS: The anatomical success rates were 95 % for the anterior vaginal wall, 99 % for the posterior vaginal wall and 94 % for the apical vaginal wall after a median 27 months of follow-up. POP-Q, UDI-6 and IIQ-7 scores, maximal flow rate and post-voiding residual urine all improved significantly after surgery. Complications included 1 case of internal bleeding, 4 cases of mesh exposure, 5 cases of recurrent prolapse that required salvage operations, and 3 cases of urine retention that required intermittent catheterization. There were no bladder or bowel injuries during surgery. CONCLUSIONS: Pelvic reconstructive surgery with the Elevate system yielded good anatomical outcomes and symptom improvement after 2 years of follow-up.