Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Impact of Hormone Replacement Therapy on Risk of Ovarian Cancer in Postmenopausal Women with De Novo Endometriosis or a History of Endometriosis.

The effect of hormone replacement therapy (HRT) on the malignant transformation of postmenopausal endometriosis remains unclear. This study aimed to investigate the impact of HRT on ovarian cancer occurrence in postmenopausal women with de novo endometriosis or a history of endometriosis. A total of 10,304 women that received HRT (the HRT group) and 10,304 that did not (the control group) were selected by 1:1 matching those that met the study criteria. Incidences of ovarian cancer (0.3% in the HRT group and 0.5% in the control group) and cumulative incidence rates of ovarian cancer were similar in the two groups. The overall mean duration of HRT was 1.4 ± 2.2 years, but the duration of HRT in women with ovarian cancer was 2.2 ± 2.9 years. After adjusting for co-variables, receipt of HRT, duration of HRT, combined use of estrogen and progesterone, and tibolone were not found to be risk factors for ovarian cancer. However, the use of estrogen alone was found to be a significant risk factor for ovarian cancer (HR 2.898; 95% CI 1.251-6.715; p = 0.013). With the exception of HRT using estrogen alone, HRT did not increase the risk of ovarian cancer in postmenopausal women with a history of endometriosis or de novo endometriosis.

Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.

The effect of postoperative hormone replacement therapy (HRT) on survival in women with ovarian cancer remains unclear. This study aimed to investigate the impact of postoperative HRT on survival in women with ovarian cancer using the nationwide cohort study. Women aged ≤60 and diagnosed with ovarian cancer that received primary surgery were followed-up for 5.6 ± 2.9 years. Mean ages of women administered HRT (the HRT group; n = 263) or not administered HRT (the control group; n = 1521) were 41.5 ± 8.5 and 41.0 ± 11.4 years, respectively. After adjustment for covariables, OS was significantly greater in the HRT group (HR 0.618; 95% CI 0.414−0.922; p = 0.018). Kaplan−Meier curve analysis showed OS was significantly higher in the HRT group (85.3% vs. 76.6%; p = 0.016). The ratio of women with HRT to women without HRT increased significantly with time (restricted mean survival times for OS, p < 0.001). In addition, OS was significantly greater for those that received HRT for >5 years than for those that received HRT for ≤0.5 years (HR 0.234; 95% CI 0.059−0.936; p = 0.040). Postoperative HRT improved survival among women with ovarian cancer. The impact of HRT on survival increased with time and treatment duration.

Chasing the structural diversity of the transcription regulator Mycobacterium tuberculosis HigA2.

Transcription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a toxin-antitoxin system is an example of negative transcriptional autoregulation: during expression of the cognate toxin it is suppressed through binding to a specific DNA sequence. In the present study, the antitoxin HigA2 from Mycobacterium tuberculosis M37Rv was structurally examined. The crystal structure of M. tuberculosis HigA2 comprises three sections: an N-terminal autocleavage region, an α-helix bundle which contains an HTH motif, and a C-terminal ß-lid. The N-terminal region is responsible for toxin binding, but was shown to cleave spontaneously in its absence. The HTH motif performs a key role in DNA binding, with the C-terminal ß-lid influencing the interaction by mediating the distance between the motifs. However, M. tuberculosis HigA2 exhibits a unique coordination of the HTH motif and no DNA-binding activity is detected. Three crystal structures of M. tuberculosis HigA2 show a flexible alignment of the HTH motif, which implies that the motif undergoes structural rearrangement to interact with DNA. This study reveals the molecular mechanisms of how transcription factors interact with partner proteins or DNA.

Impact of Progesterone on Molecular Mechanisms of Preterm Premature Rupture of Membranes.

The role and mechanisms of progesterone in preterm premature rupture of membranes (PPROM) remains unclear. This study aims to investigate the molecular mechanisms of action of progesterone in pre-labor full-term fetal amniotic membrane cells with and without stimulation by microbial, pro-inflammatory, or thrombogenic agents. Fetal amniotic membranes were collected from 30 women with a normal singleton pregnancy undergoing elective cesarean section at term prior to the onset of labor. The human amniotic epithelial cells isolated were pretreated with and without medroxyprogesterone acetate for 24 h. Then, cells were treated with and without TLR/NLR agonists, pro-inflammatory cytokines, or thrombin for 48 h. Semi-quantitative RT-PCR, Western blot, and caspase-3 activity measurement were performed. Progesterone stimulation decreased the expression of TLR2, TLR5, and Nod2 genes (alone and/or in combination with TLR/NLR agonists) and decreased the expression of IL-1ß and IL-8 genes increased by stimulation with specific agonists for TLR2, TLR4, TLR5, Nod1, and Nod2. Moreover, progesterone decreased thrombin-induced IL-8 gene expression. Progesterone also decreased expression of Bax and Bid proteins (pro-apoptotic factors) increased by stimulation with pro-inflammatory cytokines (TNF-α, NGAL, IL-18, and IL-1ß) and thrombin. Progesterone stimulation alone as well as co-stimulation with TNF-α, NGAL, IL-18, IL-1ß, or thrombin with progesterone either increased, decreased, or did not change the expression of Bcl-2, Bcl-XL, or XIAP genes (anti-apoptotic factors). These data suggest progesterone plays protective roles against PPROM through anti-microbial, anti-inflammatory, and anti-thrombogenic actions on human-term fetal amniotic membrane cells. Progesterone alters pro-inflammatory cytokine- and thrombin-induced apoptosis by controlling the expression of pro-apoptotic and anti-apoptotic factors.

Relationship between threatened miscarriage and gestational diabetes mellitus.

BACKGROUND: Both threatened miscarriage and gestational diabetes mellitus (GDM) are common complications of pregnancy. However, only one pilot study has reported that these complications are not related. We aimed to investigate whether threatened miscarriage is one of the risk factors of GDM. METHODS: An unmatched case-control study of 1567 pregnant Korean women who underwent a two-step approach to diagnose GDM was retrospectively conducted. The eligible women were classified into normal (n = 840), borderline GDM (n = 480), and GDM (n = 247) groups. We analyzed the associations with threatened miscarriage in all groups with adjustment for confounding factors. RESULTS: The proportion of women who experienced threatened miscarriage was significantly lower in the GDM group than in the normal group (adjusted odds ratio (OR), 0.38; 95% confidence interval (CI), 0.18-0.78). It was significantly lower in the maternal hyperglycemia group (borderline GDM and GDM groups) than in the normal group (adjusted OR, 0.66; 95% CI, 0.47-0.91). The proportion of women who experienced threatened miscarriage was also significantly lower in the GDM group than in the normal (adjusted OR, 0.35; 95% CI, 0.17-0.70) and borderline GDM groups (adjusted OR, 0.46; 95% CI, 0.22-0.94). Moreover, the proportion of women who experienced threatened miscarriage significantly decreased according to the severity of glucose intolerance (adjusted OR, 0.94; 95% CI, 0.76-1.16). CONCLUSION: This study demonstrates that threatened miscarriage is associated with decreased risk of GDM and the severity of glucose intolerance in Korean women. Additional studies are warranted to understand the pathophysiologic mechanisms that might exist between these frequent complications of pregnancy.

The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion. METHODS: In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria. RESULTS: The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; P = 0.001; I2, 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; P = 0.001; I2, 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; P = 0.30; I2, 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups. CONCLUSION: Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.

Barbed versus conventional 2-layer continuous running sutures for laparoscopic vaginal cuff closure.

We compared results using unidirectional barbed sutures and conventional sutures for vaginal cuff closure during total laparoscopic hysterectomy (TLH).The electronic medical records and surgical videos of 170 patients who underwent TLH between January 2013 and March 2015 at Uijeong-bu St. Mary's Hospital of Catholic University of Korea were reviewed. Vaginal cuffs were closed using the 2-layer continuous running technique with unidirectional barbed sutures (V-Loc; Covidien, Mansfield, MA) in 64 patients and with polycolic acid Vicryl; Ethicon, Somerville, NJ sutures in 106 patients. Procedure time, clinical characteristics, and postoperative complications were compared between the 2 study groups. There were no differences in clinical characteristics (age, body mass index, and demographic data) between groups. The mean suturing time was significantly reduced in the barbed group (7.2 vs 12.2 minutes; P < 0.001), although the mean number of stitches was greater than in the Vicryl group (14.1 vs 12.3, P < 0.001). Perioperative complications, including episodes of vaginal bleeding, vaginal cuff cellulitis, and postoperative fever, did not differ between groups. There were no instances of vaginal cuff dehiscence in either group. Unidirectional barbed sutures can be used safely to reduce procedure time and surgical difficulty relative to conventional sutures in laparoscopic vaginal cuff closure.

Relationship Between Gonadotropin-Releasing Hormone/Gonadotropin-Releasing Hormone Receptor Signaling and Progesterone Receptors in Human Trophoblasts.

OBJECTIVE: To investigate the relationship between gonadotropin-releasing hormone (GnRH)/gonadotropin-releasing hormone receptor (GnRHR) signaling and progesterone receptors (PGRs). STUDY DESIGN: HTR-8/SV neo cells and JEG-3 cells were incubated for 24 hours with GnRH-I or -II. The expression of PGRs was measured by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blotting. RESULTS: In both cells lines after incubation with 1-1,000 nM/L GnRH-I or -II the ratio of PGR-B to PGR-AB mRNA level did not differ in any of the groups as compared to the control. Relatively higher expression of PGR-B than PGR-A mRNA and expression of only PGR-B protein without PGR-A protein were observed in all specimens. There were no significant differences in the expression of PGR-B protein in each group when compared to the control group after incubation with GnRH-I or -II at 0.001-1,000 mM/L in both cell lines. CONCLUSION: PGRs are expressed regardless of GnRH/GnRHR signaling in human trophoblasts, in which PGR-B expression is more dominant than PGR-A expression.

Relationships among hearing loss, cognition and balance ability in community-dwelling older adults.

[Purpose] The purpose of this study was to determine the relationships among hearing loss, cognition, and balance ability in elderly individuals. [Subjects and Methods] In total, 46 elderly individuals over 65 years of age who were attending senior welfare centers participated in this study. Through a hearing test, the speech frequency pure tone average in the better ear was checked. We set a criterion of hearing loss if the better ear hearing level (BEHL) value was 25 dB or more. Cognition ability was evaluated using the Korean mini-mental state examination (K-MMSE). Dynamic balance ability was evaluated by the timed up and go (TUG) test, and static balance ability was tested using a one-leg stance test (OLST). [Results] The ages of the subjects were all related to BEHL, TUG, K-MMSE, and OLST. BEHL had a negative correlation with OLST, whereas it had no correlation with K-MMSE or TUG. The hearing loss group had a significantly shorter OLST time than the normal hearing group. [Conclusion] As elderly individuals get older, their hearing and cognition, as well as their balance abilities deteriorate. The results of this study indicate there is a significant correlation between hearing loss and static balance.

Maternal hyperglycemia and the 100-g oral glucose tolerance test.

OBJECTIVES: To compare the characteristics of pregnant women with hyperglycemia according to the severity of glucose intolerance using the 100-g oral glucose tolerance test (OGTT) and to demonstrate the need to manage the condition of women with mild hyperglycemia. MATERIALS AND METHODS: In this retrospective cohort study, a total of 258 women at high risk of gestational diabetes (GDM) based on a positive 50-g oral glucose challenge test (OGCT) were classified into 0+, 1+, 2+, 3+, and 4+ groups according to the number of abnormal plasma glucose values on the 100-g OGTT. The clinical characteristics of the groups were compared. RESULTS: The rates of advanced maternal age (≥ 35 years), multiparity, prior history of GDM, preterm birth, cesarean delivery, and elevated body mass index were all positively correlated with the number of abnormal plasma glucose values on the OGTT (p < 0.05 for all variables). After adjusting for confounding factors, the fasting plasma glucose levels predicted birth weight in 44.4%, 48.4%, and 58.6% of the women in the positive 50-g OGCT group, the 0+ group, and the 1+ group, respectively. Weight gain during pregnancy predicted birth weight in 42%, 44.6%, and 37.6% of the women in the positive 50-g OGCT group, the 0+ group, and the 2+ group, respectively (p < 0.001 in each case). CONCLUSIONS: These data demonstrate that the detection and management of mild hyperglycemia below the current diagnostic criteria of GDM as well as GDM diagnosed using the 100-g OGTT are necessary for improving pregnancy outcomes.

A Pilot Study to Investigate the Efficacy of Fibrin Sealant (Tisseel®) in the Loop Electrosurgical Excision Procedure.

AIMS: The objective of the current study was to evaluate the efficacy and feasibility of fibrin sealant (Tisseel®) in the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN 2 or 3). METHODS: We designed a single-blind, prospective, randomized study in 40 consecutive women undergoing LEEP for CIN 2 or 3 at our institute. Two milliliters of fibrin sealant (Tisseel) was applied to the uterine cervix of 20 women immediately after LEEP surgery (treatment group). We evaluated abdominal pain, vaginal bleeding, vaginal discharge and impairment in daily living after 1 week using visual analogue scale questionnaires and compared the results with those of 20 women who did not receive fibrin sealant (control group). RESULTS: Among 40 women who returned for a follow-up 1 week after LEEP, 25 women (62.5%) reported at least one moderate to severe postprocedural symptom. The mean duration of moderate to severe vaginal bleeding and impairment in daily living during postoperative week 1 for the treatment group and the control group was 0.3 ± 0.80 versus 1.7 ± 2.36 days (p = 0.015) and 0.9 ± 1.37 versus 3.00 ± 2.62 days (p = 0.060), respectively. CONCLUSION: Intraoperative application of fibrin sealant (Tisseel) in LEEP can decrease postoperative vaginal bleeding and impairment in daily living.

Association between fetal abdominal circumference and birthweight in maternal hyperglycemia.

OBJECTIVES: To compare fetal abdominal circumference and its relationship with birthweight at increasing gestational ages in the context of maternal hyperglycemia of varying severity. DESIGN: Retrospective cohort study. SETTING: Two centers participated in building one database. POPULATION: A total of 1538 Korean pregnant women were subjected to a two-step approach to diagnose gestational diabetes mellitus. METHODS: Pregnant women were classified into gestational diabetes mellitus, borderline gestational diabetes mellitus, and normal groups. Fetal abdominal circumferences, which were measured with ultrasound at 4-week intervals starting at 16 weeks of gestation and ending prior to delivery, were evaluated in the groups. MAIN OUTCOME MEASURE: The significance of fetal abdominal circumferences as predictors or risk factors of macrosomia/large-for-gestational age. RESULTS: Fetal abdominal circumferences measured from 16 weeks of gestation until prior to delivery predicted birthweight in all groups with some exceptions. Fetal abdominal circumferences measured from 32 weeks of gestation until prior to delivery were predictive of macrosomia in all groups. Fetal abdominal circumferences measured from 28 weeks of gestation until prior to delivery were predictive of neonates being large-for-gestational age in all groups. Fetal abdominal circumferences measured at 16 and 24 weeks of gestation were also predictive of large-for-gestational age in the borderline gestational diabetes mellitus group. Fetal abdominal circumference measured at 24 weeks of gestation was also a predictor of macrosomia/large-for-gestational age in normal women. CONCLUSIONS: Fetal abdominal circumferences measured during the second and especially third trimesters were significantly associated with excessive birthweight, irrespective of the severity of maternal glucose intolerance.

Pregnancy coexisting with uterus didelphys with a blind hemivagina complicated by pyocolpos due to Pediococcus infection: a case report and review of the published reports.

A woman in early pregnancy was referred due to severe pelvic pain. Vaginal examination showed a severely protruding left vaginal wall with severe tenderness. A transvaginal ultrasound showed a double uterus and a mixed echogenic mass next to the cervix of the left uterus. After creating an opening in the left vaginal wall and inserting a Foley catheter through the opening into the vaginal wall for drainage with antibiotic therapy, the patient's condition rapidly improved. A culture of the pus drained from the vaginal wall showed Pediococcus species. The patient delivered a healthy infant by cesarean section at term gestation without recurrence of pyocolpos. Ten months after delivery, resection of the vaginal septum was performed and the left cervix was exposed. Ultrasound revealed normal kidneys.

Infectious morbidity after cesarean delivery: 10 strategies to reduce risk.

Puerperal infection remains a major cause of maternal morbidity and mortality. The primary risk factor is cesarean delivery, which increases the risk 5- to 20-fold. This article reviews in detail the risk of puerperal infection following cesarean delivery, both endometritis and surgical site infection, in both high- and low-risk populations. Strategies to prevent such infections are also discussed using a systematic evidence-based approach.

Immunohistochemical evidence for the over-expression of Glutathione peroxidase 3 in clear cell type ovarian adenocarcinoma.

Glutathione peroxidase 3 (GPX3) is a member of glutathione peroxidase family, exerting one of the most important cellular defense mechanisms against stress signals, including oxidative damage. In this study, the expression of GPX3 mRNA and protein was analyzed for ovarian cancer tissues to test its applicability as a biomarker that can distinguish the four major histologic types of epithelial ovarian cancer. A public microarray dataset containing 99 ovarian cancer and 4 normal ovary samples was downloaded, and GPX3 mRNA expression was analyzed. The expression of GPX3 protein was measured by immunohistochemical staining in 40 epithelial ovarian cancer tissues, 10 for each of the serous, endometrioid, mucinous, and clear cell type. Histoscores were made from the immunohistostaining, and analysis of variance (ANOVA) was performed to quantitate the differences in protein level. Analysis of genomic dataset confirms a GPX3 overexpression in clear cell type ovarian adenocarcinoma compared with normal ovary and 3 other subtypes of epithelial ovarian cancer at mRNA level. GPX3 also shows the highest average antibody staining intensities in clear cell type ovarian adenocarcinomas over the other 3 types in immunostaining on tissue arrays. This is the first validation of GPX3 as a clear cell type-specific biomarker in ovarian cancer patients' tissues by immunostaining. GPX3 may serve as an important molecular marker for the diagnosis and molecular understanding of clear cell carcinoma of the ovary.