Asymptomatic Women Research Articles

BLADDER HEALTH IN US WOMEN: POPULATION-BASED ESTIMATES FROM THE RISE FOR HEALTH STUDY

Bladder health encompasses total bladder well-being and not merely the absence of urinary symptoms. While much is known about the prevalence of urinary symptoms in women, little is known about the distribution of bladder health (e.g., optimal to poor). We report the distributions of multiple dimensions of bladder health and function in a population-based sample of community-dwelling women, overall and separately in women without urinary symptoms to begin to explore bladder health dimensions that may precede the onset of symptoms. RISE FOR HEALTH is a regionally-representative cohort study of US women aged 18 and older. Baseline surveys included the validated Bladder Health Scales/Bladder Function Indices, the 10-item Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index, and additional study items. Bladder well-being was assessed across 10 scales and bladder function across six indices. Bladder Health Scale scores were adjusted for adaptive/coping behaviors (e.g., using/carrying pads, staying close to a toilet) to account for the perceived impact of urinary symptoms on well-being. Scores for scales and indices ranged from 0 (poor well-being/function) to 100 (optimal well-being/function). We calculated summary statistics for each scale (with and without adaptive behavior adjustment) and each index in the full study population and subset of women without urinary symptoms. The mean age of 3,027 eligible participants was 49.8 years (SD 17.9). The median global Bladder Health Scale score was 72 (IQR: 56, 84) before adjustment for adaptive/coping behaviors and 55 (IQR: 34, 78) after adjustment. Median scores for the other scales ranged from 75-100 before and 61-72 after adjustment. Sixty-nine percent of participants reported using adaptive/coping behaviors, including using pads (40%), toilet mapping (58%), and staying close to a toilet (3%). The median overall Bladder Function Index score was 77 (IQR: 63, 89); individual median scores ranged from 63-68 for frequency, sensation, continence, and emptying indices to 100 for biosis/urinary tract infection and comfort indices. Among participants without reported urinary symptoms (n=700), scores were higher across all scales (unadjusted medians=88-100 and adjusted medians=82-100) and indices (medians=93-100), indicating better, but not optimal health; however, 38% of asymptomatic women reported using adaptive/coping behaviors: 11% using pads, 30% toilet mapping, and 2% staying close to a toilet. We observed a wide range of bladder well-being and function in RISE participants, and high utilization of adaptive/coping behaviors. Bladder health variability and utilization of adaptive/coping behaviors was also observed in women without urinary symptoms, highlighting bladder health dimensions not captured by traditional urinary symptom tools and potentially identifying a group of women with "sub-clinical" symptoms who may be at greater risk of developing urinary symptoms. Future prospective analyses should investigate this novel group of women further.

Long-term prognosis of patients with an SCN5A loss-of-function variant and progressive cardiac conduction disorder or Brugada syndrome

The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown. This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events. Probands and family members with (likely-)pathogenic SCN5A loss-of-function variants were retrospectively included. Clinical and ECG data at baseline and last follow-up were collected. Patients with a history of cardiac arrest, sustained ventricular tachycardia, symptomatic or documented atrial tachy- or bradyarrhythmia, or arrhythmogenic syncope, were categorized as symptomatic. Arrhythmic events at follow-up were defined as sudden death, aborted cardiac arrest, documented ventricular fibrillation and/or sustained ventricular tachycardia. We included 615 patients (349 males, 242 probands, 157 spontaneous type-1 Brugada-ECG and 111 symptomatic at baseline). During 9.5 (5.0-14.3) years follow-up, arrhythmic events occurred in 41 patients (6.7%), equating an overall event rate of 0.7%/year; 2.0%/year in symptomatic and 0.3%/year in asymptomatic patients. In the overall study population, symptoms at baseline, male sex, and QRS prolongation were identified as independent predictors of arrhythmic events. In asymptomatic patients, also male sex and QRS prolongation were identified as predictors. Asymptomatic women with QRS <100ms did not experience arrhythmic events at follow-up. Key predictors of arrhythmic risk in patients with an SCN5A loss-of-function variant, regardless of a Brugada syndrome diagnosis, are symptoms at baseline, male sex, and prolonged QRS. Our findings may enable more tailored management strategies in patients with an SCN5A loss-of-function variant based on their individual risk profiles.

Use of ST/HR hysteresis decreases false positive rate in exercise electrocardiography test of middle-aged asymptomatic women

BackgroundExercise electrocardiography (ECG) is a common diagnostic and prognostic method for the detection of coronary artery disease (CAD). However, its accuracy in asymptomatic women has not been comprehensively investigated and the diagnostic criteria may require refinements. This study evaluated the performance of ECG-derived ST/HR-index, ST/HR hysteresis and ST-segment depression parameters among asymptomatic middle-aged women. Methods108 women (mean age 56 ± 4 years) performed exercise ECG test on treadmill until exhaustion three times within a nine-month period. False-positive rates of maximum ST/HR-index, ST/HR hysteresis, and ST-segment depression values measured from 12 leads at peak exercise and after one-minute recovery were evaluated with recommended diagnostic partition values. Repeatability was assessed with intraclass correlation (ICC) and Bland-Altman plot analysis. ResultsFalse-positive rate was lower for all variables when a two‑lead configuration was used instead of a single‑lead configuration. Using a two‑lead configuration, ST/HR hysteresis (0–1.9 %) and ST-segment depression after one-minute recovery (0–2.8 %) had lower false-positive rates compared to ST/HR index (3.7–20.4 %) and ST-segment depression at peak exercise (9.3–27.8 %). ICC values indicated moderate repeatability for ST/HR hysteresis while ST/HR index, ST-segment at peak exercise, and ST-segment after one-minute recovery had moderate-to-good repeatability. Bland-Altman analysis indicated poor repeatability for all evaluated ECG variables. ConclusionIn asymptomatic middle-aged women, practitioners should prefer the use of ST/HR hysteresis and ST-segment after one-minute recovery over the conventional ST-segment depression at peak exercise or ST/HR index, and evaluate the ECG data from a two‑lead configuration instead of single‑lead.

A Multicenter Cohort Study on DNA Methylation for Endometrial Cancer Detection in Cervical Scrapings.

The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Assessment of Nonmass Lesions Detected with Screening Breast US Based on Mammographic Findings.

Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Automated Breast Ultrasound With Remote Reading for Primary Breast Cancer Screening: A Prospective Study Involving 46 Community Health Centers in China.

Background: China has faced barriers to implementation of a population-based mammographic screening program. Breast ultrasound provides an alternative screening modality to mammography in low-resource settings. Objective: To evaluate the performance of ABUS with remote reading as the primary screening modality for breast cancer. Methods: This prospective study enrolled asymptomatic women 35-69 years old from 46 community health centers across 18 provinces representing all six regions of China from January 2021 to December 2021. Participants underwent screening ABUS as the sole breast cancer screening modality, with images acquired by a technologist at the community health center. The 3D volumetric data were transferred via cloud-based software to a single remote reading center, where examinations were interpreted independently in batches by two subspecialized breast radiologists using BI-RADS; a third radiologist at the remote reader center resolved discrepancies. Diagnostic reports were returned to the community centers, and patients sought follow-up care at local hospitals. The reference standard incorporated a combination of histopathology and 24-month follow-up. Outcomes measures included cancer detection rate, abnormal interpretation rate (AIR), sensitivity, specificity, biopsy rate, and PPV. Results: The final analysis included 5978 enrolled participants (median age, 46 years [IQR 40-52 years]) who underwent screening ABUS at the community health centers with subsequent remote reading. A total of 24 ABUS-detected cancers and two interval cancers were diagnosed. The cancer detection rate was 4.0 per 1000 women (95% CI: 2.7-5.9), and the AIR was 11.9% (95% CI: 11.1-12.7). A total of 95.8% (23/24) of ABUS-detected cancers were invasive. The 23 invasive cancers had a median diameter of 10.0 mm; 73.9% (17/23) were node-negative. Sensitivity was 92.3% (95% CI: 75.9-97.9), and specificity was 88.4% (95% CI: 87.6-89.2). The biopsy rate was 1.7% (95% CI: 1.4-2.0), and the PPV of biopsy was 24.0% (95% CI: 16.7-33.2). Conclusion: ABUS screening with remote reading met benchmark performance for cancer detection in comparison to mammography, with infrequent interval cancers. Clinical Impact: ABUS with remote reading holds promise in enhancing access to breast cancer screening and early detection in low-resource settings or underserved regions where mammographic screening is not established.

Unus Pro omnibus, omnes Pro uno: a commentary on the eternal dilemma of endometrial cancer screening in postmenopausal asymptomatic women. Is it time to team up?

Introduction The diagnostic workflow for endometrial carcinoma in postmenopausal asymptomatic women remains an ongoing dilemma. Whereas an ultrasonographic endometrial thickness greater than 4.0 or 5.0 mm is adequate for warranting further investigations in women with postmenopausal vaginal bleeding, there is still no unanimous consensus on what the ideal endometrial thickness cut-off should be, justifying additional inspection through endometrial sampling when bleeding is absent. Methods A comprehensive overview of the most recent literature to summarize the clinical pathway necessary for the diagnostic assessment of a postmenopausal asymptomatic woman with increased ultrasonographic endometrial thickness. Results An endometrial thickness cut-off between 3.0 and 5.9 mm seems to show the lowest specificity while also reducing the chances of missing malignancy. If endometrial thickness can be a valid starting point, a careful evaluation of the other ultrasonographic endometrial features and a thorough scrutiny of patients’ risk factors are pivotal to standardizing the diagnostic process while avoiding overtreatment. Although preventing unnecessary procedures is crucial, stratifying the risk and proceeding with further investigations (preferably through outpatient or office hysteroscopically-guided targeted biopsies) should be the goal. Conclusions Closer collaboration between different fields of medicine (ultrasonography, hysteroscopy, and oncology) is strongly encouraged to facilitate early diagnosis of asymptomatic postmenopausal women at risk of developing endometrial malignancy.

BREATH TEST TO DETECT WOMEN AT LOW RISK FOR BREAST CANCER: POTENTIAL CLINICAL AND ECONOMIC BENEFITS.

A breath test for volatile organic compounds has identified biomarkers associated with breast cancer. We evaluated the potential clinical and economic benefits of a breath test to detect women at low risk for breast cancer by comparing its negative predictive value (NPV) to the NPV of screening mammography. Sensitivity and specificity values for screening mammography were obtained from the Food & Drug Administration Mammography Quality Standards Act; Amendments to Part 900 Regulations Docket No. FDA-2013-N-0134. The high values were sensitivity = 79.0%, specificity = 88.9% and the low values were sensitivity = 66.0%, specificity = 88.9%. In two previous studies of 771 women undergoing mammography, breath testing identified breast cancer with sensitivity=84% and specificity = 68.6% in 178 asymptomatic women, and sensitivity=82% and specificity = 77% in 593 who were symptomatic. These values were projected to a hypothetical screening population of 100,000 asymptomatic women with average breast cancer prevalence of 450/100,000, in order to estimate the NPV and PPV (positive predictive value) for breath testing and screening mammography respectively. Breath test in asymptomatic women: NPV = 99.895% and PPV = 1.19%; in symptomatic women: NPV = 99.895% and PPV = 1.59%. For screening mammography, NPV = 99.83% and PPV = 2.82% (low values), increasing to NPV= 99.89% and PPV = 3.12% (high values). A negative breath test identified 68.3% of the screening population as having low risk of breast cancer, with NPV similar to mammography. Based on Medicare reimbursement rates, elimination of mammography in women with a negative breath test could reduce the annual cost of breast cancer screening by 38.9. In a hypothetical screening population, a negative breath test ruled out breast cancer with the same accuracy as a negative mammogram. A screening breath test could potentially eliminate the need for two thirds of all mammograms and reduce the costs of screening without increasing the risk of false-negative findings. If applied in clinical practice, this approach could potentially reduce the costs and burdens of breast cancer screening services, and benefit women by lessening the discomfort, anxiety, radiation exposure, and costs associated with mammography.

Co-infection of human papillomavirus and herpes simplex virus-2 with cervical dysplasia among women in Kaduna State, Nigeria

Background: The epidemiology of human papillomavirus (HPV) and co-infections with herpes simplex virus type 2 (HSV-2) remains poorly characterized in Africa. High risk HPV (hrHPV) infection is the primary cause of 99.7% all cervical cancer especially in the presence of genital ulcer disease (GUD) which is usually caused by HSV-2. Herpes simplex virus-2 might interact directly with hrHPV to increase the risk of cervical cancer. Co-infection of HPV and HSV-2 in asymptomatic women could provide a clue to early diagnosis of cervical cancer and this could aid in the development of new strategies for effective management and improvement of the quality of life of women who are infected. If the synergy between HPV and HSV-2 can be prevented, there may be significant reduction of the incidence of cervical cancer. Methodology: This was a descriptive cross-sectional study of 515 randomly selected apparently healthy women of reproductive age whose cervical samples were screened for HPV and HSV-2 in Kaduna State, Nigeria. The cervical samples were collected by liquid-based cytology (LBC) for detection of cervical epithelial cell abnormalities (CEA) and molecular detection of HPV and HSV-2 using conventional polymerase chain reaction (PCR) assay. Extracted viral DNAs from the samples were amplified by convectional PCR using specific hrHPV (HPV 16,18, 31 and 45) primer sets and a broad spectrum MY09/11 and GP5+/6+ primers for a wider range of HPV genotypes while HSV-2 DNA was detected by florescence-based PCR assay with HSV-2 gG primers and probes. Results: PCR assay revealed that 14.7% (n=76) of the 515 selected women harbored HPV, HSV-2 or both. The prevalence of HPV, hrHPV, HSV-2 and HPV/HSV-2 co-infection among in the study participants are 11.8% (n=61), 9.3% (n=48), 5.6% 4% (n=29) and 2.3% (n=12) respectively. The frequency of HPV detection in HSV-2 infected participants (41.4%, 12/29) was significantly higher (OR=6.295, p&lt;0.0001) than in HSV-2 negative participants (10.1%, 49/437), but only co-infections of HPV-31 (p=0.004) and HPV-18 (p=0.040) with HSV-2 were significantly associated. Cervical cytology reports on the smears revealed prevalence of cervical epithelial abnormalities (CEA) of 16.7% (n=86), with cervical dysplasia prevalence of 6.4% (n=33), consisting of high grade squamous intraepithelial lesion (HGSIL) of 1.6% (n=8), low grade squamous intraepithelial lesion (LGSIL) of 4.1% (n=21) and atypical squamous cells of uncertain significance (ASCUS) of 0.8% (n=4). The frequency of HPV detection in women with cervical dysplasia (93.9%, 31/33) was significantly higher (OR=14.22, p&lt;0.0001) than in women without cervical dysplasia (6.2%, 30/482), and all HPV genotypes were significantly associated (p&lt;0.05) with cervical dysplasia except HPV 16 (p=0.051). Also, the frequency of HPV/HSV-2 co-infection among women with cervical dysplasia (15.2%, 5/33) was significantly higher than among women without cervical dysplasia (1.5%, 7/482) (OR=12.12, p&lt;0.0001). Comparing women with cervical inflammatory and atrophic changes (n=53), women with cervical dysplasia (HGSIL, LGSIL and ASC-US) had significantly higher frequency of HPV infection (χ2=42.829, p=0.000), HSV-2 infection (χ2=25.140, p=0.001) and HPV/HSV-2 co-infections (χ2=66.602, p=0.000). Conclusion: Co-infection rate of hrHPV and HSV-2 among women in Kaduna State is 2.3%. Demographic factors significantly influencing the rate of co-infections included age and marital status. In spite of the screening method using the traditional Pap smear, GUD and cervical cancer continues to be a major public health problem, thus more sensitive and specific methods such as liquid based cytology technique and polymerase chain reaction for early detection of cervical dysplasia and hrHPV or HSV-2 in asymptomatic women should be adopted for routine use

Rate of preterm delivery and latency period in asymptomatic patients undergoing cerclage for very short cervix ≤10.0 mm

AimTo estimate the rate of preterm delivery (PTD) and mean latency period to delivery in asymptomatic women with no history of preterm delivery and cervical length (CL) ≤10.0 mm undergoing or not cerclage and who were not treated with vaginal progesterone. MethodsRetrospective analysis of asymptomatic patients with singleton pregnancies and no history of preterm delivery, with an incidental finding of a CL ≤10.0 mm measured with transvaginal ultrasound during the mid-trimester scan, 56 of them (63.6%) underwent cerclage placement and 32 (36.4%) did not, none of them received vaginal progesterone. Those with evidence of advanced dilation, prolapsing, membranes, ruptured membranes, or positive signs of infection were not candidates for cerclage placement were excluded from the analysis. Differences in the prevalence of preterm birth, mean gestational age at delivery, and mean latency from very short cervix identification to delivery between the two groups were calculated. Associations between cerclage and preterm delivery adjusted for maternal characteristics and fetal weight, were estimated. ResultsMedian (range) gestational age at time of CL measurement in the cerclage group was (weeks/days) 20w6d (17w5d–23w3d) vs. 21w5d (17w6d–23w6d) in the no-cerclage group (p=0.02). No differences in CL were observed between those who had a cerclage (5.9 mm (SD 3.1 mm)) vs. those who did not (6.5 mm (SD 3.2 mm); p=0.4). The prevalence of preterm delivery (PTD) in women with cerclage vs. women without cerclage was: PTD <37 weeks 31/56 (55.3%) vs. 28/32 (87.5%); adjusted (a) OR 0.17 (95% CI; 0.05-0.62 p=0.008); PTD ≤34 weeks 27/56 (48.2%) vs. 24/32 (75.0%); aOR 0.16 (95% CI 0.05-0.55; p=0.02); PTD ≤28 weeks 19/56 (33.9%) vs. 22/32 (68.7%); aOR 0.15 (95% CI 0.05-0.51; p=0.002). The mean (range) gestational age at delivery was 32w6d (19w1d–40w1d) for the cerclage group, and 28w1d (20w1d–40w2d) for the no-cerclage group (p =0.001). The median (range) latency from the time of CL measurement to delivery in the cerclage group was 84 (8-144) vs. 43 (1-146) days in the no-cerclage group (p=0.003). ConclusionAmong low-risk asymptomatic women with a very short cervix (≤10.0 mm) in the midtrimester scan, those treated with cerclage have increased latency to delivery and lower prevalence of preterm birth as compared to expectant management.

Vulvovaginal candidiasis in pregnant women attending a tertiary care centre in North-Eastern India

BackgroundCandida colonisation in vagina was found to be 20 %, rising to 30 % during pregnancy. According to studies, the prevalence of VVC during pregnancy is higher than healthy women. During pregnancy, candidal colonisation increases, both symptomatic and asymptomatic. However, the difference between strains causing symptomatic infection and those that cause asymptomatic infection is unknown. ObjectiveThis study aimed to compare the virulence factors of Candida VVC isolates from symptomatic and asymptomatic pregnant women. MethodsThe study included 120 pregnant women- 60 symptomatic and 60 asymptomatic, who presented to the Obstetrics and Gynaecology Outpatient Department with vaginitis symptoms. High vaginal swabs from the patient and used for gram stain, direct wet mount, pH detection and fungal culture in SDA with and without antibiotics. Germ tube tests, growth in CMA, and HiCrome Candida Differential Agar were used to identify yeast colonies grown in culture. The isolates were then examined for virulence factors like biofilm formation, phospholipase, coagulase, and hemolysin. Antifungal susceptibility was determined using E-test. ResultsThe current study reveals a high prevalence of Vulvovaginal Candidiasis in pregnant women(35 %). Asymptomatic patients had lower proportion of VVC than symptomatic patients. Non albicans Candida(NAC) outnumbered Candida albicans. Although Candida albicans growth was predominant in asymptomatic patients. Virulence studies revealed that Candida spp. isolated from symptomatic patients expressed a higher proportion of virulence factors. Besides NAC has higher proportion of expressing virulence factors than Candida albicans and has higher propensity to cause infection especially in symptomatic pregnant women. Antifungal susceptibility testing shows Itraconazole to be most sensitive for VVC treatment but Candida albicans was most susceptible to fluconazole while NAC had the least. ConclusionsThe study emphasizes the importance of routine screening of symptomatic pregnant women for VVC, as syndromic treatment will increase antifungal resistance, particularly in NAC.

B-308 Analytical and clinical performance of a novel ovarian cancer screening test in asymptomatic women

Abstract Background Ovarian cancer (OC) ranks among the deadliest gynecological cancers, often diagnosed at advanced stages when treatment options are limited. Costly sequencing methods and established immunoassay and imaging-based methods lack early-stage sensitivity, highlighting the need for a cost-effective test with improved performance. Extracellular vesicles (EVs) produced in abundance by all cells can potentially improve test sensitivity and detection of multiple colocalized cancer specific markers can improve test specificity. The randomized controlled trial UKCTOCS (United Kingdom Collaborative Trial of Ovarian Cancer Screening) where over 200,000 postmenopausal asymptomatic women were randomly assigned to three arms revealed no significant reduction in mortality with OC screening. We report on an EV-based OC Test performance in serum samples from asymptomatic postmenopausal women in UKCTOCS. Methods The OC Test was previously locked (biomarkers, method, cutoff) and validated in an independent cohort. We evaluated the OC Test in a blinded case-control study nested within the no screening (NS) and annual ultrasound screening (USS) arms of UKCTOCS. All UKCTOCS participants provided a blood sample at study entry. Cases were all women who developed high grade serous ovarian cancer (HGSOC) within 36 months following sample donation (spun within 28 hours). They were matched by age at collection (+/-2 years) to women who had no OC detected either before or within the trial follow up period (controls). Where a case had &amp;gt;1 sample within the 0-36 months period, the control sample was matched to the case sample closest to diagnosis. The OC Test was run with a locked method and classifier algorithm utilizing 3 independent biomarker combinations tested in duplicate. OC Test results were calculated based on a previously determined cutoff prior to unblinding of clinical outcomes. Run controls were prepared by harvesting conditioned media from COV413A cell cultures (an ovarian epithelial-serous carcinoma cell line), purifying EVs and spiking into pre-screened OC Test negative human plasma at three levels. Run controls were run twice per day, one replicate per run for 17 days. Results We retrospectively assessed 116 samples from 108 cases (63 clinical Dx NS, 15 clinical Dx USS, 30 screen detected USS) women with HGSOC and 1310 samples from 1310 controls. OC test sensitivity for HGSOC was 84% (36/43; 95% CI 69%-93%), Stage I/II sensitivity was 89% (8/9; 95% CI 51%-99%) and the AUC (area under the curve) was 0.93 for case samples drawn 0-12 months prior to clinical Dx and all control samples. The OC Test specificity was 98% (1099/1176, 95% CI 97%-98%). Within laboratory CVs were 20.9%, 12.7% and 0.6% for low negative, high negative and high positive run controls respectively. Data from 143 samples (10%, 9 cases, 134 controls) were excluded due to operator error, low sample volume or quality issues. Conclusions The OC Test is capable of highly sensitive detection of HGSOC within one year of clinical diagnosis including at the earliest stages of disease while maintaining exceptionally high specificity. The results demonstrate the potential application of the OC Test for ovarian cancer screening in asymptomatic women.

A Deeper Look at Office Hysteroscopy in Asymptomatic Postmenopausal Patients: indications and outcomes of 822 Cases.

Study ObjectiveThis study aims to assess the prevalence of malignancy and other endometrial pathologies in asymptomatic postmenopausal women referred for office hysteroscopy, identify main referral indications, and assess their relationship with the risk of malignancy.Secondary objectives included evaluating the association between ultrasound variables and malignancy risk and assessing procedure validity, which encompasses duration, feasibility and patient comfort during office hysteroscopy. DesignRetrospective analysis. SettingThe study was conducted at the Department of Gynecology, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia's largest tertiary care center. ParticipantsThe cohort consisted of 822 asymptomatic postmenopausal women referred for office hysteroscopy, excluding those with postmenopausal bleeding within the last year. InterventionsParticipants underwent office hysteroscopy with or without biopsy. Measurements and Main ResultsThe main indication for hysteroscopy was ultrasound abnormalities alone, with remaining indications including a combination of ultrasound and clinical findings. Among the cohort, 97.4% exhibited benign findings, while 2.6% were diagnosed with cancer or precancerous lesions. The analysis revealed that patients with indications based on ultrasound and clinical findings suggestive of malignancy had a higher risk of malignancy compared to those with ultrasound alone. In 387 patients with documented ultrasound variables, inhomogeneous endometrial appearance (OR: 8.2, 95% CI: 2.4-27.9, p<0.001) and significant liquid content within the uterine cavity (OR: 10.2, 95% CI: 3.6-28.9, p<0.001) exhibited strong associations with malignancy. Analysis of the procedure revealed a high feasibility rate (87.8%), with a median duration of 13,7 minutes and a median VAS pain score after the procedure of 3/10. ConclusionsThe prevalence of endometrial cancer and precancerous lesions in asymptomatic postmenopausal patients is likely low, with most intrauterine pathologies being benign. Our study demises the utility of routine endometrial surveillance for this population in the absence of specific risk factors. A holistic approach, considering individualized assessments and factors beyond endometrial thickness, is crucial in interpreting ultrasonic findings.

Retrospective analysis of 3a obstetric anal sphincter injury repairs in a teaching hospital: Subjective and objective outcomes

IntroductionThe Royal College of Obstetricians and Gynaecologists (RCOG) recommends offering elective caesarean sections (CS) to patients with anorectal dysfunction, or abnormal endoanal ultrasonography (EAUSS) or anal manometry following obstetric anal sphincter injury (OASI) for subsequent deliveries. (1) Asymptomatic OASI patients however, are not always offered these investigations due to limited access to diagnostic resources across the United Kingdom, particularly those with 3a tears. This paper reviews subjective and objective outcomes in women with 3a tears and aims to add to the body of literature supporting good practice and management of these patients. ObjectivesIdentify the incidence of defects in patients with 3a tears following a primary repair and compare the rate and extent of defects found on EAUSS between symptomatic and asymptomatic women. Study DesignWe performed a retrospective study of 69 women following primary repair of 3a OASI tears in a tertiary referral perineal clinic between January 2020 and December 2022. Symptoms were evaluated using the St Mark’s Score for anal incontinence (SMI) and Starck score for defects on EAUSS. Findings were analyzed using R Foundation Statistical Software (version 4.2.2, 2022). ResultsOut of the total, 42 % (29/69) had defects on EAUSS and 30 % (21/69) of women were symptomatic. Thirty eight percent (18/48) of asymptomatic women were noted to have defects compared with 52 % (11/21) of symptomatic patients. Majority of defects were situated in the upper and mid anal canal (69 %) either as <1 hr or >3 hr hypoechoic areas. There was no significant difference in Starck score (2.23 v 1.53, p = 0.46) between the two groups but those delivered by forceps (p = 0.004) and Asian ethnicity (p = 0.01) were more likely to be symptomatic. ConclusionEAUSS should be offered to all patients following an OASI as symptoms alone are not predictive of anorectal compromise in structure and/or function. Asymptomatic patients with 3a tears should be informed that there is up to a 40% chance of finding a defect on EAUSS.

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Prevalence of bacterial vaginosis, sexually transmitted infections and their association with HPV infections in asymptomatic women attending antenatal care in Ethiopia.

Sexually transmitted infections (STIs) and human papillomavirus (HPV) infections are common among women of reproductive age and can lead to infertility, adverse pregnancy outcomes, neonatal infections and cervical cancer. In countries with limited medical coverage, untreated infections contribute to high morbidity. This study aimed to expand the current knowledge on the prevalence of bacterial vaginosis (BV) and STIs in pregnant Ethiopian women and assess the association of these conditions with HPV infections. Socio-demographic data and vaginal lavage samples were collected from 779 asymptomatic women aged 18 to 45 years (median age, 25.9 years) attending antenatal care in seven centres across Ethiopia. Multiplex polymerase chain reaction was used to test for BV, Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, herpes simplex virus types 1 and 2 (HSV-1/2), Mycoplasma, Ureaplasma, Candida species and HPV. Overall, 26.8% (95% confidence interval (CI): 23.7-29.9) of women tested positive for BV or one of the following STIs: C. trachomatis, T. vaginalis, N. gonorrhoeae, Mycoplasma genitalium, HSV-1/2 or Ureaplasma urealyticum. Additionally, 22.1% tested positive for at least one high-risk HPV type. Chlamydia trachomatis and HSV-2 were significantly more common among women who were positive for HPV and high-risk HPV. This study reveals a high prevalence of asymptomatic pregnant women who are positive for BV, STIs or HPV, putting them at risk of adverse pregnancy outcomes, secondary infertility or cervical cancer in a country with limited medical coverage. Screening and treating these women could be crucial in reducing morbidity.

Plasma Inflammatory Proteome Profile in a Cohort of Patients with Recurrent Vulvovaginal Candidiasis in Kenya.

Vulvovaginal candidiasis (VVC) affects up to 75% of women at least once during their lifetime, and up to 8% of women suffer from frequent recurrent episodes of VVC (RVVC). A lack of a protective host response underlies vaginal Candida infections, while a dysregulated hyperinflammatory response may drive RVVC. This study aimed to investigate the systemic inflammatory protein profile in women with RVVC in an African population, considering the potential influence of hormonal contraceptive use on systemic inflammation. Using multiplex Proximity Extension Assay technology, we measured 92 circulatory inflammatory proteins in plasma samples from 158 RVVC patients and 92 asymptomatic women (controls). Hormonal contraceptive use was not found to have a statistically significant correlation with a systemic inflammatory protein profile in either RVVC patients or the asymptomatic women. RVVC women had lower circulating Fibroblast Growth Factor 21 (FGF-21) concentrations compared with healthy controls (adjusted p value = 0.028). Reduced concentrations of FGF-21 may be linked to the immune pathology observed in RVVC cases through IL-1β. This study may help to identify new biomarkers for the diagnosis and future development of novel immunomodulatory treatments for RVVC.

Management After Obstetric Anal Sphincter Injury: Anorectal Manometry and Symptoms Predict Long-Term Fecal Incontinence.

Obstetric anal sphincter injury (OASI) is associated with serious morbidity and reduced quality of life. The role of anorectal manometry (ARM) to guide treatment is unclear. We aimed to define the role of ARM and symptom assessment after OASI in predicting anal incontinence at long-term follow-up. Prospective evaluation of 205 consecutive post-OASI women who underwent baseline ARM and symptom assessment in a tertiary setting was undertaken. Ninety-nine women were available for long-term follow-up (median 6.6 years). Associations between post-OASI ARM testing and short-term and long-term anal incontinence were examined in addition to clinical and obstetric factors. Fourth degree tears and lower anal resting and squeeze pressures were associated with short-term anal incontinence. Women with anal incontinence at baseline and women with lower anal resting pressure were more likely to suffer from long-term fecal incontinence (FI). A best-fit cutoff value of 59 mm Hg for baseline anal resting pressure predicted long-term FI, and none of the short-term asymptomatic women with an anal resting pressure of >59 mm Hg reported FI at long-term follow-up. Symptoms of anal incontinence and ARM in patients after OASI are both useful to predict subsequent long-term FI with a best-fit cutoff of 59 mm Hg for anal resting pressure. This provides rationale for routine ARM and accurate symptom assessment in all patients after OASI, to identify high-risk groups to follow and treat, and it may assist decision making regarding mode of subsequent obstetric deliveries.

A Comparative Analysis of the Bleeding Profile and Quality of Life Among Women With Hemophilia Genotype Compared to Other Bleeding Disorders.

Introduction Women with bleeding disorders continue to be underdiagnosed as well as undertreated. Women with bleeding disorders include those with genotype for hemophilia (traditionally named hemophilia carriers), von Willebrand disease (VWD), platelet function disorders, and rare bleeding disorders. Among these women, the carriers of hemophilia are usually considered asymptomatic. The present study compares the bleeding profile and quality of life (QOL) of women and girls with hemophilia and compares it to those diagnosed with VWD and rare bleeding disorders. Methods The present study is part of a prospective observational study (August 2023-July 2028) done on women and girls >12 years in two groups. Group 1 was mothers, sisters, or daughters of patients with hemophilia A who were proven carriers. Group 2 was girls and women registered at our center as following bleeding symptoms and diagnosed as either suffering from VWD or rare bleeding disorders. The bleeding profile was assessed by 1:1 interview using the International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT). Health-related QOL (HRQOL) was assessed using the EuroQOL five dimension (EQ5D5L) questionnaire. Results The baseline data collected in the first six months of this prospective study is being presented here. At the time of submission, the center caters to 970 patients with hemophilia and inherited bleeding disorders. Eighty girls (post pubertal) and women with either obligate carrier status for hemophilia (n=68) or a previously diagnosed bleeding disorder (10 VWD, one afibrinogenemia, one factor VII deficiency) were enrolled.The median age of Group 1 was 35 years (25-70 years), whereas that of Group 2 was 15.5 years (13-23 years). In Group 1 (women and girls with hemophilia (WGH)), 58 and 10 were carriers of hemophilia A and B, respectively. Additionally, 83% of WGH had more than one family member with bleeding disorder, whereas 75% of Group 2 had a positive family history. The number of family members with the same disorder ranged from 0-4. Among 68 hemophilia carrier women, 20 reported bleeding symptoms (29.4%), of which 18 reported menorrhagia, one antepartum hemorrhage, and one post-partum hemorrhage and two had joint/muscle bleeds and one each had ENT and gastrointestinal bleeding. Three of them were admitted for treatment of excessive bleeding and treated with plasma/red cells. Three women reported gynecological procedures for excessive bleeding, one was on treatment for ovarian cysts, and four received packed red cells after delivery. The BAT score above 6 was reported only in 10% of WGH. Eighteen patients had undergone a surgical procedure in their life, and three of these women required a transfusion during surgery. Only one woman reported similar complaints in her daughter. The comparative analysis of HRQOL showed a significantly worse score for Group 1 in EQ5D5L domains for pain and anxiety/depression compared to that of Group 2. Conclusions A significant proportion of previously asymptomatic women with hemophilia carrier status were recognized to have significant bleeding tendencies. The QOL of these carriers is comparable to girls with VWD and rare bleeding disorders and requires special attention.

Chlamydia Trachomatis Prevalence in Asymptomatic Women in Madrid: Study Findings and Their Association with Risk Factors and Mental Health.

Chlamydia trachomatis (CT) is a sexually transmitted infection that requires early detection to prevent complications. This study aimed to evaluate the prevalence of CT among asymptomatic women in Spain and investigate the relationship between CT and risk factors associated with sexual practices, as well as factors such as stress and depression. We found that 3.8% of asymptomatic women tested positive for CT. Our findings suggested that having more than five sexual partners increases the risk of sexually transmitted infections (STIs) by 3.87 times when compared with having fewer partners (p = 0.005, OR: 3.87, 95% CI 1.24-11.65). Additionally, 4.5% of participants admitted to using drugs. We found that there was a slightly higher proportion of anxiety and depression among women who tested positive for CT. We aimed to establish a basis for the implementation of screening in asymptomatic women. Early identification and preventive measures are crucial in minimizing the long-term complications and transmission of the disease. Sexual behavior must be recognized as a risk factor, and women's psychological well-being should be given top priority as a vital aspect of their sexual health.