Cumulative Effects of Comorbid Burden and Overactive Bladder Symptoms on Fall Risk Among Older Women Seeking Treatment for Urogynecologic Conditions.

IMPORTANCE: Overactive bladder (OAB) syndrome and urinary incontinence, age, and comorbid burden are strong risk factors for falls in women. Less is known about their cumulative effects on fall risk in a urogynecologic population. OBJECTIVE: The purpose of this study was to investigate the effects of coexisting OAB, older age, and comorbidities on risk of falling among treatment seeking women with pelvic floor disorders. STUDY DESIGN: We conducted a retrospective medical records review of 348 consecutive women presenting to a urogynecology clinic over 6 months. Fall risk was determined by the Centers for Disease Control and Prevention's, Stopping Elderly Accidents, Deaths, and Injuries screening tool. Clinical and sociodemographic measures were abstracted from the electronic medical record. Odds of screening positive for high fall risk based on different patient profiles were calculated. We then used a classification and regression tree analysis to determine the relative importance of the different variables on fall risk within the homogeneous subgroups. RESULTS: Of the 348 women (mean age, 58.7 ± 15.8 years) who completed the fall risk screen, 124 (36%) screened positive for increased fall risk. Overactive bladder symptoms increased the likelihood of a positive fall risk screen across all combinations of age and comorbid burden. The patient profile of ≥3 OAB symptoms, ≥4 comorbid conditions, and age 65 years or older increased the odds of screening positive for high fall risk more than 6-fold (odds ratio, 6.4; 95% confidence interval, 3.1-12.9). In the following order of importance, the combination of high comorbid burden, OAB, and older age identified approximately 3 in 4 patients (73.3%) at high risk of falling. CONCLUSION: The presence of 3 easily identifiable patient characteristics is strongly associated with a risk of falls in women seeking care for pelvic floor disorders.

Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study.

Uterine leiomyomas are complex tumours with limited medical treatment options. Simvastatin is used to treat hypercholesterolaemia and has shown promising effects as a treatment option for leiomyomas. Previously, our group demonstrated a promising effect of simvastatin treatment in a patient-derived xenograft mouse model. Here, we tested the efficacy of simvastatin liposomal nanoparticles (NPs). After bilateral leiomyoma xenograft implantation, mice (N = 12) were divided into three treatment arms: control, simvastatin and simvastatin-loaded liposome NPs (simvastatin-NPs). Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP; however, the results were not significant. Due to low bioavailability and short half-life of simvastatin, liposomal NPs have the potential to enhance drug delivery, however, in this study NP did not provide improvement over simvastatin, but did demonstrate their potential for the delivery of simvastatin.Impact statementWhat is already known on this subject? Simvastatin treatment in a patient-derived xenograft mouse model reduced tumour growth and decreased proliferation.What do the results of this study add? Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP, however, it did not improve the efficacy of simvastatin at reducing tumour growth and proliferation.What are the implications of these findings for clinical practice and/or further research? More studies are needed to optimise the formulation of NPs to further enhance the sustainable delivery of simvastatin.

Prevalence and Predictors of Increased Fall Risk Among Women Presenting to an Outpatient Urogynecology and Pelvic Health Center.

OBJECTIVES: The objective of this study was to determine the prevalence of increased fall risk among women presenting to a large pelvic health center using a screening method compatible with the busy clinic environment and to identify factors associated with increased risk. METHODS: A retrospective medical records review was conducted on consecutive treatment-seeking women presenting to a Urogynecology & Pelvic Health Center over 6 months. The Centers for Disease Control and Prevention, Stopping Elderly Accidents, Deaths, and Injuries fall risk screening tool was included among the intake questionnaires all patients completed before their scheduled appointments. Relevant sociodemographic and clinical measures were abstracted from the electronic medical record. RESULTS: Three hundred and forty-eight women completed the fall screen. One hundred and twenty-four (36%) screened positive for increased fall risk. Mean age was 58.7 ± 15.8 years. An age threshold of 68 years best discriminated between those who were and were not identified as at risk. There was a gradient of association between number of urinary symptoms and prevalence of increased fall risk. Patients with 3 or more urinary symptoms were most likely to screen positive (1: odds ratio [OR], 1.51 [0.86-2.66]; 2: OR, 1.62 [0.99-2.64]; 3 or more: OR, 1.84 [1.07-3.17]) after adjusting for other know fall risk factors. CONCLUSIONS: The prevalence of increased fall risk in this patient population is high and highest in women with multiple urinary symptoms. The Stopping Elderly Accidents, Deaths, and Injuries screening tool was a feasible and nonintrusive screening method for identifying increased fall risk during routine patient care. Fall risk and concern about falling should be taken into consideration when deciding management strategies for urinary problems.

Predictors of same-day discharge after minimally invasive hysterectomy for benign indications.

OBJECTIVE: To identify predictors of same-day discharge after benign minimally invasive hysterectomy. METHODS: In this retrospective cohort study, we identified women (n = 1084) undergoing benign minimally invasive hysterectomy from 2009 to 2016. Multivariate logistic regression was used to examine demographic, operative, and surgeon factors associated with discharge on postoperative day 0. RESULTS: In our study population, 238 women (22%) were discharged on the same day. Robotic hysterectomy (risk ratio [RR] 2.24; 95% confidence interval [CI] 1.13-4.44), shorter operative time (lowest quartile; RR 5.28; 95% CI 2.66-10.46), and minimal blood loss (lowest quartile; RR 3.01; 95% CI 1.68-6.23) were associated with higher same-day discharge likelihood whereas later procedure start time (2-5 pm; RR 0.38; 95% CI 0.17-0.85) and postoperative complications (RR 0.19; 95% CI 0.06-0.55) significantly decreased its likelihood. The strongest predictor was surgeon's number of years in practice, with recently graduated surgeons more likely to discharge their patients on the same day (RR 3.15; 95% CI 2.09-4.77). CONCLUSION: Same-day discharge after minimally invasive hysterectomy is determined by several patient, operative, and surgeon factors that can be incorporated into an implementation plan to promote earlier discharge. Most especially, scheduling patients based on perceived case complexity and targeted surgeon education can qualify a larger cohort for same-day discharge.

Safety and efficacy of robotic-assisted Burch for pure stress urinary incontinence: a large case series.

Burch urethropexy is one of the earliest and most effective surgeries for stress urinary incontinence. Minimally invasive robotic surgery is becoming more popular in the field of urogynecology. Herein, we present the safety and efficacy of a large case series of robotic-assisted Burch urethropexy. A retrospective chart review was performed on robotic-assisted Burch urethropexy cases performed between 2013 and 2019. Patient characteristics, perioperative data and follow-up outcomes were collected at a single teaching institution. A total of 76 women underwent robotic-assisted Burch urethropexy for pure stress urinary incontinence. Fifty of them had concomitant robotic procedures at the time of the Burch. We performed the robotic-assisted Burch urethropexy alone on 26 patients. The mean age was 55 years old. The overall treatment success rate was 85% with a mean follow-up time of 134 (±157.8) days. Complications included cystotomy (3%), urinary tract infection (16%) and postoperative voiding dysfunction (10%). Our study reveals that robotic-assisted Burch urethropexy is a feasible option in the treatment of stress urinary incontinence in terms of operative outcomes and short-term efficacy.Impact statementWhat is already known on this subject? Minimally invasive robotic surgery is becoming more popular in the field of urogynecology. Surgical repairs for stress urinary incontinence will likely increase in the coming years secondary to an aging population. Burch urethropexy is one of the earliest and most effective surgeries for stress urinary incontinence and can be performed abdominally, laparoscopically and now, using robotic assistance.What do the results of this study add? This study reveals that robotic-assisted Burch urethropexy is a feasible option in the treatment of stress urinary incontinence in terms of intraoperative outcomes with good short-term efficacy.What are the implications of these findings for clinical practice and/or further research? Lately, interest in colposuspension procedures has been rekindled as physicians seek alternative stress urinary incontinence treatment options. Robotic-assisted Burch urethropexy will continue to gain popularity with its efficacy and safety.

Predictors of the cost of hysterectomy for benign indications.

INTRODUCTION: Hysterectomy is a commonly performed procedure with widely variable costs. As gynecologists divert from invasive to minimally invasive approaches, many factors come into play in determining hysterectomy cost and efforts should be sought to minimize it. Our objective was to identify the predictors of hysterectomy cost. MATERIALS AND METHODS: This was a retrospective cohort study where women who underwent hysterectomy for benign conditions at the University of Texas Medical Branch from 2009 to 2016 were identified. We obtained and analyzed demographic, operative, and financial data from electronic medical records and the hospital finance department. RESULTS: We identified 1,847 women. Open hysterectomy was the most frequently practiced (35.8 %), followed by vaginal (23.7 %), laparoscopic (23.6 %), and robotic (16.9 %) approaches. Multivariate regression demonstrated that hysterectomy charges can be significantly predicted from surgical approach, patient's age, operating room (OR) time, length of stay (LOS), estimated blood loss, insurance type, fiscal year, and concomitant procedures. Charges increased by $3,723.57 for each day increase in LOS (P <0.001), by $76.02 for each minute increase in OR time (P <0.001), and by $48.21 for each one-year increase in age (P 0.037). Adjusting for LOS and OR time remarkably decreased the cost of open and robotic hysterectomy, respectively when compared with the vaginal approach. CONCLUSION: Multiple demographic and operative factors can predict the cost of hysterectomy. Healthcare providers, including gynecologists, are required to pursue additional roles in proper resource management and be acquainted with the cost drivers of therapeutic interventions. Future efforts and policies should target modifiable factors to minimize cost and promote value-based practices.

Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model.

Uterine leiomyomas represent a challenging problem with limited medical treatment options. The anti-tumor agent 2-methoxyestradiol (2-ME) shows promising results but its efficacy is limited by inadequate pharmacokinetics. We previously demonstrated that 2-ME nanoparticles can be successfully formulated and that they show improved in vitro anti-leiomyoma cell activity. Here, we examined the effects of the in vivo delivery of 2-ME nanoparticles in a patient-derived xenograft (PDX) leiomyoma mouse model. Patient-derived leiomyoma tumor tissues were xenografted subcutaneously in estrogen/progesterone pretreated immunodeficient NOG mice. Animals (n = 12) were treated with liposomal 2-ME nanoparticles by intra-peritoneal (IP) injection (50 mg/kg/dose, three times weekly) or control for 28 days. Tumor volume was measured weekly by calipers and prior to sacrifice by ultrasound. In addition, the expression of the cell proliferation marker Ki67 and the apoptosis marker cleaved caspase-3 in tumor tissues after treatment were measured by immunohistochemistry. Liposomal 2-ME treatment was associated with a significant tumor growth inhibition (30.5% less than controls as early as 2 weeks, p = 0.025). In addition, injections of liposomal 2-ME inhibited the expression of the proliferation marker Ki67 (55.8% reduction, p < 0.001). Furthermore, liposomal 2-ME treatment was associated with a 67.5% increase of cleaved caspase-3 expression of increase (p = 0.048). Our findings suggest that liposomal nanoparticle formulation can successfully deliver 2-ME and can be a promising therapeutic strategy for uterine leiomyoma. Further characterization of the liposomal-2ME, including pharmacokinetics, maximal tolerated dose, and safety, is needed in preclinical models prior to clinical trials.

Association of preoperative sleep pattern with posthysterectomy pain: a pilot study.

STUDY OBJECTIVES: To evaluate the association of preoperative sleep pattern with posthysterectomy pain perception and satisfaction with surgery. METHODS: This pilot study included women undergoing minimally invasive hysterectomy for benign conditions. Sleep quality, insomnia severity, and insomnia risk were assessed pre- and postoperatively via standard questionnaires. Total sleep time, wake after sleep onset, and sleep efficiency were measured before and after hysterectomy using daily sleep diaries and wrist-worn actigraphy. Pain perception and satisfaction with hysterectomy were assessed postoperatively. Repeated-measures analysis of variance, Pearson's correlation, and linear regression were used for analysis. RESULTS: Twenty women participated; of them 16 had complete data and were analyzed. Total sleep time increased from 384 ± 102 minutes before to 468 ± 96 minutes after surgery (P = .023). Wake after sleep onset, a measure of sleep fragmentation, increased from 26 ± 15.1 minutes before to 52 ± 22.9 minutes after surgery (P = .014). Pearson's correlation showed preoperative total sleep time was inversely correlated with postoperative pain intensity (r = -.92, P = .01). Preoperative wake after sleep onset was positively correlated with postoperative pain intensity (r = .86, P = .008). Preoperative insomnia severity and insomnia risk were positively associated with postoperative pain and pain behaviors (ß = 0.41, P < .05; ß = 0.55, P < .01, respectively). Finally, preoperative sleep efficiency was positively associated with overall satisfaction with hysterectomy (ß = 0.39, P < .05). CONCLUSIONS: Sleep duration and fragmentation increase following hysterectomy. Shorter, more fragmented preoperative sleep is associated with greater postoperative pain intensity. Better preoperative sleep was associated with more satisfaction after hysterectomy. Further studies are needed to determine if preoperative sleep interventions such as cognitive behavioral therapy improve pain perception and satisfaction after hysterectomy.

Pelvic Pain and Apical Prolapse Surgery: A Population-Based Retrospective Cohort Study.

OBJECTIVES: The aims of this study were to evaluate the association of preoperative pelvic pain with operative characteristics and the association of patient and operative characteristics with postoperative pain. METHODS: This is a retrospective cohort study utilizing Clinformatics DataMart, a large national commercial insurance database. We collected data for patients older than 18 years who underwent apical prolapse surgery between January 2005 and December 2014. We stratified data by preoperative (prior) pain and analyzed for associations of prior and postoperative pain. Logistic regression analysis was performed using SAS software. RESULTS: A total of 14,440 patients met inclusion criteria and were analyzed. Patients with prior pain were more likely to have an abdominal (open or laparoscopic) approach, a concomitant hysterectomy, but less likely to have additional repairs or a mesh insertion (P < 0.001). Postoperative pain was less with a concomitant hysterectomy, whether they had prior pain (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.41-0.77) or not (OR, 0.68; 95% CI, 0.56-0.82). Additional vaginal repairs were associated with more postoperative pain for those without prior pain (OR, 1.63; 95% CI, 1.3-2.04). Age older than 45 years was associated with less pain. Length of hospital stay of more than 2 days was associated with more pain. CONCLUSIONS: Patients with prior pain were more likely to undergo an abdominal approach and have a concomitant hysterectomy. Postoperative pain was less with a concomitant hysterectomy, but more with additional vaginal repairs. There is a need to include pain as an outcome in future studies, particularly clinical trials.

Short-term results of changes in existing and de novo lower urinary tract symptoms after robot-assisted laparoscopic uterosacral ligament suspension and sacrocolpopexy.

OBJECTIVE: This study presents short-term outcomes related to changes in existing and de novo lower urinary tract symptoms (LUTS), pelvic pain, and bowel function following robot-assisted laparoscopic uterosacral ligament suspension (RALUSLS) and sacrocolpopexy (RALSC). METHODS: Observational data for RALUSLS (n = 23) and RALSC (n = 25) collected between August 2014 and March 2016 from a single institute (The University of Texas Medical Branch) were evaluated retrospectively. Patient characteristics, concomitant procedures, and the occurrence of lower urinary tract, pelvic pain, and bowel symptoms were compared between patients undergoing RALUSLS and RALSC. RESULTS: There was no significant difference in background characteristics between the 2 groups, except for parity, which was high in the RALUSLS group. In the RALUSLS group, patients experienced significant resolution of urinary urgency (P < .001) and frequency, urge and mixed incontinence, and pelvic pain (P < .05). In the RALSC group, there was significant resolution of nocturia, mixed incontinence, pelvic pain, and dyspareunia (P < .05). There was no significant difference in the occurrence of de novo symptoms in the RALUSLS and RALSC groups (P > .05), although newly appearing urinary urgency or frequency and stress or urge incontinence were more common after RALSC. CONCLUSION: Mixed incontinence and pelvic pain improved significantly in patients after RALUSLS or RALSC. In RALUSLS patients, urgency, frequency, and urge incontinence also improved, whereas additional improvement in nocturia and dyspareunia was evident only in RALSC patients. De novo LUTS developing after these procedures, especially after RALSC, necessitate careful patient consultation prior to surgery.

Erratum to "Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases".

[This corrects the article DOI: 10.1155/2017/5316845.].

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost.

OBJECTIVE: Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. MATERIAL AND METHODS: We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. RESULTS: Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. CONCLUSION: PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits.

Therapeutic Roles of Statins in Gynecology and Obstetrics: The Current Evidence.

INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate-limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition of downstream products of this pathway, which explains the pleiotropic effects of these agents in addition to their well-known lipid-lowering effects. Accumulating evidence suggests that statins might be beneficial in various obstetric and gynecologic conditions. METHODS: Literature searches were performed in PubMed and EMBASE for articles with content related to statins in obstetrics and gynecology. The findings are hereby reviewed and discussed. RESULTS: Inhibition of mevalonate pathway leads to subsequent inhibition of downstream products such as geranyl pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. These products are required for proper intracellular localization of several proteins, which play important roles in signaling pathways by regulating membrane trafficking, motility, proliferation, differentiation, and cytoskeletal organization. The pleiotropic effects of statins can be summarized in 4 categories: antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic. The growing body of evidence is promising for these agents to be beneficial in endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome. Although in vivo studies showed varying degrees of benefit on fibroids and preterm birth, appropriately designed clinical trials are needed to make definitive conclusions. CONCLUSION: Statins might play a role in the treatment of endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome.

Endometrial myomectomy: a novel surgical method during cesarean section.

STUDY OBJECTIVE: Comparing surgical outcomes of a novel surgical technique endometrial myomectomy (EM) to serosal myomectomy (SM) during ceserean section (CS). DESIGN: Retrospective cohort study (Canadian task force classification level II 1). SETTING: Private hospital. PATIENTS: Fourty-six women with leiomyomas during cesarean section Interventions: Endometrial myomectomy and serosal myomectomy during cesarean section between 2013 and 2016. MAIN OUTCOME MEASURES: Total 22 consequtive cases (Group 1) underwent EM in the last 2 years. The control group created from SM (Group 2) cases performed before EM implemented in our practice. Group 2 was matched based on anteriorly located intramural or submucosal leiomyoma. The size, location and number of leiomyoma, hematological course during pre- and postoperative period, the need for blood transfusion, duration of surgery, and any prolongation of hospital stay also documented. RESULTS: Median number of leiomyoma was higher in EM than in SM (p = 0.001). Median myomectomy procedure time and amount of intra-operative bleeding in SM were higher than EM (respectively, p = 0.005 and p = 0.001). In terms of other variables, there is no difference between the two myomectomy groups (p > 0.05). CONCLUSION: This novel technique EM is a safe, feasible surgical technique compared with SM. Besides the less intra-operative blood loss, it also has the potential to diminish the risk of abdominal adhesion formation.

Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases.

The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2; FAKpY397; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.

Medicolegal Review of Methotrexate Administration to Viable Intrauterine Pregnancies.

Objective: To examine 3 legal cases in which physicians prescribed methotrexate to women with a viable intrauterine pregnancy, presumed to be ectopic, resulting in adverse fetal outcomes. Study Design: We conducted an electronic literature search for legal cases using the keywords "methotrexate" and "pregnancy" in the LexisNexis legal research engine as well as an Internet-wide search using the additional keyword "verdict." We manually searched the resultant list of identified cases and categorized the studies identified in the search by verdict, award amount, and outcome of the embryo exposed to methotrexate. Results: The monetary awards are typically greater when the embryo exposed to methotrexate lives and requires continuous medical and custodial care as compared to when the fetus dies in utero or shortly after birth. Conclusion: Physicians who, with all good intentions, prescribe methotrexate to women with a viable pregnancy, presumed to be ectopic, could find them-selves liable for an adverse fetal outcome. For the benefit of patients, their unborn offspring, and the liability exposure of the physician, it is important to be very cautious when prescribing methotrexate.

Estrogen Receptors and Signaling in Fibroids: Role in Pathobiology and Therapeutic Implications.

Uterine fibroids are the most common gynecologic tumors with a significant medical and financial burden. Several genetic, hormonal, and biological factors have been shown to contribute to the development and growth of fibroid tumors. Of these factors, estrogen is particularly critical since fibroids are considered estrogen dependent because no prepubertal cases have been described in the literature and tumors tend to regress after menopause. Understanding the role of estrogen in fibroids is not only important for understanding the pathobiology of fibroids but also for the development of successful therapeutics. In this review, we discuss the types and structure of estrogen receptors (nuclear and membrane bound, including α and ß receptors and G protein-coupled estrogen receptor 1 GPER1). Estrogen-signaling pathways in fibroids include genomic (direct and indirect) and nongenomic including Ras-Raf-MEK (MAPK/Erk Kinase)-mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)-phosphatidylinositol-3,4,5-trisphosphate (PIP3)-Akt (Protein kinase B)-mammalian target of rapamycin (mTOR) pathways; shortly Ras-Raf-MEK-MAPK and PI3K-PIP3-Akt-mTOR pathways. Several aberrations in estrogen receptors and signaling pathways are implicated in fibroid pathobiology. Current therapeutic and research agents targeting ERs/signaling include gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, aromatase inhibitors, selective ER modulators, gene therapy, and others. Future research can identify potential targets for the development of novel treatments. In particular, epigenomics of estrogen activity and individualized (precision) medicine appear to be attractive areas for future research.

A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells.

OBJECTIVE: Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). STUDY DESIGN: The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. RESULTS: 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. CONCLUSION: Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors.

Management of the Jehovah's Witness in Obstetrics and Gynecology: A Comprehensive Medical, Ethical, and Legal Approach.

IMPORTANCE: Obstetricians and gynecologists frequently deal with hemorrhage so they should be familiar with management of patients who refuse blood transfusion. Although there are some reports in the literature about management of Jehovah's Witness patients in obstetrics and gynecology, most of them are case reports, and a comprehensive review about these patients including ethicolegal perspective is lacking. OBJECTIVE: This review outlines the medical, ethical, and legal implications of management of Jehovah's Witness patients in obstetrical and gynecological settings. EVIDENCE ACQUISITION: A search of published literature using PubMed, Ovid Medline, EMBASE, and Cochrane databases was conducted about physiology of oxygen delivery and response to tissue hypoxia, mortality rates at certain hemoglobin levels, medical management options for anemic patients who refuse blood transfusion, and ethical/legal considerations in Jehovah's Witness patients. RESULTS: Early diagnosis of anemia and immediate initiation of therapy are essential in patients who refuse blood transfusion. Medical management options include iron supplementation and erythropoietin. There are also some promising therapies that are in development such as antihepcidin antibodies and hemoglobin-based oxygen carriers. Options to decrease blood loss include antifibrinolytics, desmopressin, recombinant factor VII, and factor concentrates. When surgery is the only option, every effort should be made to pursue minimally invasive approaches. CONCLUSION AND RELEVANCE: All obstetricians and gynecologists should be familiar with alternatives and "less invasive" options for patients who refuse blood transfusions.