Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications.

BACKGROUND: Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract METHODS: Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1-10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota. RESULTS: We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70-82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation. CONCLUSIONS: Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.

A New Practical Surgical Technique for Hymenoplasty: Primary Repair of Hymen With Vestibulo-Introital Tightening Technique.

BACKGROUND: Hymenoplasty is distinct from other genital surgeries with its ethical and psychological issues. It is performed to narrow the vaginal opening to ensure vaginal bleeding with penetration. There are various kinds of techniques with different success rates. OBJECTIVES: The authors sought to report a new hymenal reconstruction technique with vestibulo-introital tightening with the results of 145 procedures. METHODS: The new technique included a diamond-shaped incision to the vestibulum with the base in the posterior midline and superior corner 2 to 3 cm higher above the hymen. The angles were accommodated according to the degree of tightening, and the submucosal layer was closed from the apex downwards involving the vaginal mucosa. RESULTS: The satisfaction rate of the patients was 99.3%. No adverse events were observed. CONCLUSIONS: Compared with previous techniques described, this hymenal reconstruction technique is an alternative with the advantage of low risk of loosening because the tension on the hymen alone is decreased. Additional tightening of the introitus increases the satisfaction rates in some patients.

Fetal sex prediction measuring yolk sac size and yolk sac-fetal pole distance in the first trimester via ultrasound screening.

PURPOSE: The aim of the study was to determine the accuracy of fetal sex definition by measuring the yolk sac size and the yolk sac-fetal pole distance in the first trimester via ultrasound (US) screening. METHODS: We enrolled 92 gestational women in this prospective study. In the first trimester of US examination, the gestational sac, the gestational sac-fetal pole distance, and the yolk sac size were measured. When the fetal pole was in the longitudinal position, the distance between the fetal pole and the yolk sac was measured in millimeters (mm). The crown-rump length (CRL) was measured in the same position. US examination at 22 weeks was performed to determine whether the fetal gender was male or female. The genders of the fetuses were recorded. The sexes were also confirmed and recorded after birth. RESULTS: Fifty-five (59.8%) of the newborns were found to be male, while 37 (40.2%) of them were found to be female. We compared the yolk sac size and the yolk sac-fetal pole distance in both the female and male groups. We found that the genders showed a significant difference in terms of yolk sac-fetal pole distance, whereas the yolk sac size showed no significant difference between the genders. The optimal cutoff value of the yolk sac-fetal pole distance was 1.80 mm, with 70% sensitivity and 67% specificity for female gender prediction. The distance also showed an independent association with gender prediction in the first trimester. CONCLUSION: Yolk sac-fetal pole distance may have the potential to predict gender in the first trimester of pregnancy.

Transabdominal ultrasonography: A non-invasive method for diagnosing vaginal atrophy.

OBJECTIVE: Genitourinary syndrome of menopause is a definition of all symptoms caused by hypoestrogenemia in menopausal age and one of the most common symptoms is vaginal atrophy. The diagnosis methods which are used for vaginal atrophy may be painful. A novel method total vaginal thickness and total mucosal thickness measuring could be determine vaginal atrophy. MATERIAL AND METHODS: This is a prospective case-control study involving 60 women in each group of 120 patients. One of the groups is comprised postmenopausal, histopathologically diagnosed vaginal atrophic women and the other group comprised 24-35 aged women who were no symptoms of vaginal atrophy and vaginal swab samples are not compatible with vaginal atrophy. All women who participated in the study underwent transabdominal ultrasound and total vaginal thickness and total mucosal thickness were measured. RESULTS: Total vaginal thickness and total mucosal thickness were found lower in the postmenopausal group compared to premenopausal women (p = 0.005 and p = 0.07, respectively). The cutoff value was determined as 8.55 mm for total vaginal thickness and 1.52 mm for total mucosal thickness, and the diagnostic power of these values is a specificity of 88.89% (95% confidence interval: 51.75-99.72%) and a ppv of 92.86% (95% confidence interval: 66.53-98.84%) for total vaginal thickness and a specificity of 80.95% (95% confidence interval: 58.09-94.55%) and a ppv of 89.47% (95% confidence interval: 71.10-96.71%) for total mucosal thickness. CONCLUSION: Vaginal atrophy is a painful symptom for menopausal women and the diagnostic methods may be invasive and painful too. Total vaginal thickness and total mucosal thickness measuring with transabdominal ultrasound could be an alternative method for diagnosis and treat vaginal atrophy easily.

The histopathological results of vestibulectomy specimens in localized provoked vulvodynia in Turkey.

INTRODUCTION: Localized Provoked Vulvodynia (LPV) is a gynecological disease that is difficult to manage. Despite the wide spectrum of pathophysiological mechanisms and treatment modalities, there is limited success in the management of this disease. Surgical treatment is usually performed as the last resort. We aimed to investigate the histopathological results of 38 women with LPV who underwent surgical vestibulectomy. METHODS: of the 55 women that were diagnosed with LPV and underwent vulvar vestibulectomy, 38 patients with complete histopathological results were included in this retrospective study. RESULTS: in 14 patients, the pathological reports revealed Low-Grade Squamous Intraepithelial Lesions (LGSIL) (36.8%) whereas for 21 cases (55.2%), the findings were concordant with vestibulitis. The remaining three patients (7.8%) were diagnosed with lichen simplex chronicus. CONCLUSION: the presence of LGSIL in the surgical specimens of LPV cases is noteworthy. In this group of patients, surgical excision may contribute to the prevention of progression into high-grade lesions. The relationship between Human Papilloma Virus (HPV) infections and LPV should be further investigated.

Decreased levels of liver-expressed antimicrobial peptide-2 and ghrelin are related to insulin resistance in women with polycystic ovary syndrome.

Liver-expressed antimicrobial peptide 2 (LEAP-2) is a newly identified peptide hormone involved in glucose metabolism. It acts as a noncompetitive antagonist of ghrelin hormone's receptor. Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disease associated with insulin resistance. We aimed to compare circulating LEAP-2 levels in subjects with PCOS and controls. We also focused to determine whether there was a relationship between LEAP-2 and metabolic parameters in women with PCOS. We enrolled 64 subjects with PCOS and 64 age and body mass index (BMI)-matched controls into the current cross-sectional study. Circulating LEAP-2 and ghrelin levels were measured via ELISA method. Metabolic and hormonal parameters of the involved subjects were analyzed. We found that circulating LEAP-2 and ghrelin levels were decreased in women with PCOS as compared with controls. LEAP-2 showed a positively independent association with ghrelin while LEAP-2 exhibited an inverse association with insulin resistance, BMI, and free-androgen index (FAI). Additionally, subjects having the lowest tertile of LEAP-2 were in positive link of developing PCOS risk with respect to those subjects having the highest tertile of LEAP-2 levels. Decreased LEAP-2 levels were associated with a high possibility of having PCOS risk associated with insulin resistance.

Correlation of Swede score colposcopy scoring system and histopathological results in patients with high-risk HPV infection other than HPV16 and 18.

OBJECTIVE: Triage with HPV genotyping has some caveats and debates for HPV positive cases other than 16 and 18. The Swede score colposcopic scoring system has not previously been evaluated in this group of patients. OBJECTIVE: To use the Swede score colposcopic scoring system to compare scores and final histopathological results in women who have undergone colposcopy owing to infection with high risk-HPVs other than HPV16 and 18 and to establish new cut-off values to predict pre-malignant lesions in this group of patients. METHODS: This study was conducted in 613 women undergoing colposcopic evaluation because of abnormal cervical cytology together with high-risk HPV infection. All patients referred were evaluated by an expert colposcopist, given a Swede score (using the Swede score colposcopic scoring system) by using five variables (acetowhiteness, margins plus surface, vessel pattern, lesion size, and iodine staining), and had at least one biopsy procedure (either colposcopically directed or by a loop electrical excision procedure). Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio values, and receiver operating characteristic curves for each clinico-pathological variable to detect low-grade and high-grade squamous intra-epithelial lesions, and any squamous cell abnormality (low-grade + high-grade squamous intra-epithelial lesions) were evaluated individually. RESULTS: Final histopathological results of the patients were normal in 53.2% of cases, low-grade lesions in 32.5% of cases, and high-grade lesions in 14.4% of cases. Swede score was ≥8 (median 7.97) for high-grade lesions and ≥5 (median 5.06) for low-grade lesions. The area under the curve values (95% CI) of Swede scores for low-grade and high-grade squamous intra-epithelial lesions, and low-grade + high grade lesions were 0.92, 0.98, and 0.96, respectively. A Swede score cut-off value ≥6 had a sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios of 92%, 98%, 93%, 98%, and 50 (22.6 to 110.8), respectively, for high-grade lesions at the final pathology (P<0.001). One high-risk HPV type (except 16 and 18) was no better than another for calculating the median Swede score during colposcopy (P=0.43). CONCLUSIONS: The Swede score colposcopic scoring system appears to be a useful tool for evaluating atypical cervical cytology in women with high-risk HPV infection other than HPV types 16 and 18.

An investigation of vitamin and mineral supplement recommendation among first-trimester pregnancies.

Background Healthy and balanced nutrition in pregnancy can affect the mother's and the fetus' health. Therefore, health professionals should provide information about this issue to pregnant women. The aim of the study was to examine the rate of vitamin and mineral supplement recommendation among first-trimester pregnant women. Methods The study sample consisted of 697 first-trimester pregnant women between 18 and 40 years of age. The pregnant women who registered to an obstetric outpatient clinic between January and June 2018 were retrospectively reviewed, and data were collected from patient medical records using a questionnaire. Results Physician's laboratory test orders from the women included the following: ferritin was 18.4%, mean corpuscular hemoglobin (MCH) was 99.7%, folic acid was 10.2%, vitamin D was 6.3%, vitamin B12 was 17.2% and calcium was 20.4%. All of the women's hemoglobin levels had been examined. A total of 58.8% of the women were recommended to take folic acid, 32.7% iron, 25.7% iodine, 18.8% calcium, 17.2% vitamin A, 21.1% vitamin B12, 17.4% vitamin C, 31.6% vitamin D and 17.5% vitamin E supplements. Conclusion It was determined that ferritin, vitamins B12 and D, calcium, folic acid, iron and iodine levels were not examined routinely in this study. Folic acid and iron supplementation were the most commonly suggested nutrient supplements in the first trimester.

Evaluation of occult uterine leiomyosarcomas.

OBJECTIVES: To determine the frequency of occult uterine leiomyosarcomas following hysterectomies and myomectomiesperformed for benign reasons at our clinic and to draw comparisons with similar studies in the literature. MATERIAL AND METHODS: All hysterectomies and myomectomies that have been performed for benign reasons at our clinicbetween 2010 and 2017 were retrospectively examined via the hospital's information system and the patients that werefound to have leiomyosarcomas were analysed. The incidence of occult uterine leiomyosarcoma per 1000 surgeries at ourclinic was calculated using the Wilson score interval. RESULTS: A total of 6,173 hysterectomies were performed, and occult uterine leiomyosarcoma was identified in 5 patients. Theincidence of occult uterine leiomyosarcoma was calculated to be 0.08% (95% CI 0.03-0.018%). Only 1 of the 771 patientswho underwent myomectomy was identified with occult uterine leiomyosarcoma, making its incidence in myomectomy0.12% (95% CI 0.02-0.073%). When all the patients are considered, occult uterine leiomyosarcoma was identified in 6 of the6,944 patients, and the general incidence of occult uterine leiomyosarcoma was calculated as 0.08% (95% CI 0.03-0.018%). CONCLUSIONS: In our study, the incidence of occult uterine sarcoma following myomectomy and hysterectomy was foundto be lower than that reported in the literature. The reason for this lower incidence includes not only genetic causes andracial differences but also preoperative imaging, endometrial and cervical sampling that is performed on every patient.

Association of decreased C1q/tumor necrosis factor-related protein-5 levels with metabolic and hormonal disturbance in polycystic ovary syndrome

Objective: C1q/tumor necrosis factor-related protein-5 (CTRP5) is a novel peptide hormone involved in the metabolism of energy regulation. Polycystic ovary syndrome (PCOS), which is a reproductive and metabolic disorder, is associated with insulin resistance. The aim of the current study was to compare circulating levels of CTRP5 in women with and without PCOS and to investigate possible associations between CTRP5 and metabolic-hormonal parameters. Material and Methods: The present cross-sectional study contained 80 women with PCOS and 80 age and body mass index-matched women without PCOS. Circulating levels of CTRP5 were calculated using an enzyme-linked immunosorbent assay. We also measured hormonal and metabolic parameters. Results: Patients with PCOS had lower levels of circulating CTRP5 compared with women without PCOS (6.90±2.64 vs 11.73±3.66 ng/mL, p<0.001). CTRP5 was negatively correlated with insulin resistance, free-androgen index, and body mass index in both the PCOS and control groups. Moreover, patients with PCOS who had insulin resistance showed lower circulating CTRP5 levels compared with those without insulin resistance. In both the control and PCOS groups, overweight subjects had lower circulating levels of CTRP5 compared with participants of normal weight. Logistic regression analyses indicated that subjects in the lowest tertile for CTRP5 level had higher risk for PCOS compared with those in the highest tertile of CTRP5. Conclusion: Decreased circulating levels of CTRP5 were associated with higher risk of PCOS, as well as having metabolic disturbance among women with PCOS.

Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome.

Asprosin associated with insulin resistance is a newly discovered peptide hormone. The peptide promotes hepatic glucose production. Polycystic ovary syndrome (PCOS) is a metabolic disorder. Insulin resistance plays a vital role in the pathogenesis of the disease. The aim of this study was to discover the association between insulin resistance and asprosin in women with PCOS. We recruited 78 subjects with PCOS and 78 age-matched and body mass index (BMI)-matched controls into this cross-sectional study. Circulating asprosin levels were validated using ELISA method. We also determined metabolic and hormonal parameters of the involved subjects. We found that circulating asprosin levels were elevated in women with PCOS with respect to controls. Asprosin levels showed a positive correlation with insulin resistance, BMI, and free androgen index (FAI). Moreover, subjects with the highest tertile of asprosin levels represented increased odds of having PCOS as compared to those subjects with the lowest tertile asprosin levels. Increased asprosin levels resulted to high possibility of having PCOS risk associated with insulin resistance.

Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

Background: Lynch syndrome is an inherited cancer disorder that causes an increased lifetime risk of various types of cancers. Endometrial cancer is the most common extracolonic cancer in Lynch syndrome. Guidelines recommend that patients with endometrial cancer younger than 50 years of age should be evaluated for Lynch syndrome. Molecular analysis of the mismatch repair genes and EPCAM gene is required for a definitive diagnosis of Lynch syndrome. Aims: To report the mutation analysis of mismatch repair genes using targeted next-generation sequencing in endometrial cancer diagnosed patients <50 years of age. Study Design: Retrospective cross-sectional study. Methods: Seventy-nine endometrial cancer diagnosed patients <50 years of age underwent genetic counseling. They were selected among 1094 consecutive endometrial cancer patients between 2006 and 2017. Molecular analysis of MLH1, MSH2, and MSH6 genes was performed in 79 patients by using next-generation sequencing. Deletion/duplication analysis of mismatch repair genes and EPCAM gene was also performed in 79 patients by using the multiplex ligation-dependent probe amplification method. Results: Germline testing of mismatch repair genes was performed in 79 endometrial cancer patients. Lynch syndrome was confirmed in 4 patients (5%; 4/79). A total of 14 variants (6 in MSH2, 5 in MLH1, 3 in MSH6 genes) were found in 14 patients. Four variants were assessed as pathogenic/likely pathogenic, and 10 variants were assessed as variants of uncertain significance. Conclusion: Lynch syndrome should be investigated in patients diagnosed with endometrial cancer that are less than 50 years of age due to the increased lifetime risk of developing cancer.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. METHODS: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. RESULTS: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 µg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001). CONCLUSIONS: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.

Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

Comparison of transvaginal sonography, saline infusion sonography, and office hysteroscopy in reproductive-aged women with or without abnormal uterine bleeding.

OBJECTIVE: To compare the diagnostic accuracy and acceptability of transvaginal sonography (TVS), saline infusion sonography (SIS), and office hysteroscopy (OHS) for detecting intracavitary abnormalities in women with or without abnormal uterine bleeding (AUB). DESIGN: Prospective double-blind study. SETTING: Zekai Tahir Burak Women's Health Education and Research Hospital, Gynecology Clinic (Ankara, Turkey). PATIENT(S): A total of 26 women with AUB and 24 women without AUB were enrolled in this study. INTERVENTION(S): Transvaginal sonography, SIS, and OHS were performed on women scheduled for hysterectomy. MAIN OUTCOME MEASURE(S): Sensitivity, specificity, and positive and negative predictive values of TVS, SIS, and OHS to detect intracavitary abnormalities (with histopathologic findings used as the gold standard), duration of procedure, and pain scores. RESULT(S): The sensitivity and specificity of TVS, SIS, and OHS in detecting intracavitary abnormalities were 56.3% and 72%, 81.3% and 100%, and 87.5% and 100%, respectively. The prevalence of endometrial polyps was not different in women with and without AUB. Saline infusion sonography was less painful than OHS (pain scores of 4.3 and 7.2, respectively). CONCLUSION(S): The diagnostic accuracy of SIS was equal to that of OHS in diagnosing intracavitary abnormalities. Moreover, SIS was less painful than OHS for patients.