Multiplexed serum biomarkers to discriminate nonviable and ectopic pregnancy.

OBJECTIVE: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. DESIGN: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location. SETTING: Three university hospitals. PATIENTS: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages. INTERVENTIONS: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location.

Breast cancer dataset with biomarker Biglycan.

This dataset is composed of photomicrographs of the immunohistochemical expression of Biglycan (BGN) in breast tissue, with and without cancer, using only the staining of 3-3' diaminobenzidine (DAB), after processing images with color deconvolution plugin, from Image J. The immunohistochemical DAB expression of BGN was obtained using the monoclonal antibody (M01) (clone 4E1-1G7 - Abnova Corporation, mouse anti-human). Photomicrographs were obtained, under standard conditions, using an optical microscope, with UPlanFI 100x objective (resolution: 2.75 mm), yielding an image size of 4800 × 3600 pixels. After color deconvolution, the dataset with 336 images was divided into 2 two categories: (I) with cancer and (II) without cancer. This dataset allows the training and validation of machine learning models to diagnose, recognize and classify the presence of breast cancer, using the intensity of the colors of the BGN.

Deep learning neural network image analysis of immunohistochemical protein expression reveals a significantly reduced expression of biglycan in breast cancer.

New breast cancer biomarkers have been sought for better tumor characterization and treatment. Among these putative markers, there is Biglycan (BGN). BGN is a class I small leucine-rich proteoglycan family of proteins characterized by a protein core with leucine-rich repeats. The objective of this study is to compare the protein expression of BGN in breast tissue with and without cancer, using immunohistochemical technique associated with digital histological score (D-HScore) and supervised deep learning neural networks (SDLNN). In this case-control study, 24 formalin-fixed, paraffin-embedded tissues were obtained for analysis. Normal (n = 9) and cancerous (n = 15) tissue sections were analyzed by immunohistochemistry using BGN monoclonal antibody (M01-Abnova) and 3,3'-Diaminobenzidine (DAB) as the chromogen. Photomicrographs of the slides were analysed with D-HScore, using arbitrary DAB units. Another set (n = 129) with higher magnification without ROI selection, was submitted to the inceptionV3 deep neural network image embedding recognition model. Next, supervised neural network analysis, using stratified 20 fold cross validation, with 200 hidden layers, ReLu activation, and regularization at α = 0.0001 were applied for SDLNN. The sample size was calculated for a minimum of 7 cases and 7 controls, having a power = 90%, an α error = 5%, and a standard deviation of 20, to identify a decrease from the average of 40 DAB units (control) to 4 DAB units in cancer. BGN expression in DAB units [median (range)] was 6.2 (0.8 to 12.4) and 27.31 (5.3 to 81.7) in cancer and normal breast tissue, respectively, using D-HScore (p = 0.0017, Mann-Whitney test). SDLNN classification accuracy was 85.3% (110 out of 129; 95%CI = 78.1% to 90.3%). BGN protein expression is reduced in breast cancer tissue, compared to normal tissue.

Diagnosing ectopic pregnancy using Bayes theorem: a retrospective cohort study.

OBJECTIVE: To verify the accuracy of an online algorithm using Bayes' theorem for diagnosing ectopic pregnancy (EP) using human chorionic gonadotropin (hCG), ultrasound, and clinical data in a real cohort. DESIGN: A retrospective cohort study. SETTING: Gynecologic emergency unit in a tertiary teaching hospital. PATIENT(S): First-trimester pregnant women who attended the gynecologic emergency unit for any reason. Those who had <13 weeks of pregnancy confirmed by a recent positive pregnancy test; a digital image or electronic report of transvaginal ultrasound (TVUS) obtained from hospital database; and a follow-up with a pathology report or a clinical resolution of a confirmed pregnancy were included in the study. Clinical signs and symptoms, the presence of risk factors for EP, the TVUS findings in each consultation, and the hCG levels were independent variables obtained from the electronic medical records. From these data, the pretest probability, based on the clinical presentation and risk factors, and the likelihood ratio for each variable were calculated for their use in the algorithm, yielding a posttest probability. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE(S): The accuracy of the online algorithm to identify cases of EP using clinical signs and symptoms, the presence of risk factors for EP, the TVUS findings in each consultation, and the hCG levels. The main outcome was EP, confirmed either by pathology report or by the presence of fetal heartbeat or gestational sac outside the uterine cavity. RESULT(S): Between January 1, 2009 and December 27, 2016, 2,495 women were analyzed, and the algorithm was applied to 2,185 of them. The incidence of EP was 8.5% (212/2,495); 310 women were excluded because they were submitted to surgery with decision thresholds <95%. The algorithm was applied to 2,185 women. Just one case remained inconclusive after 3 consultations, and it was considered as an error in prediction. The sensitivity, specificity, and accuracy values (95% confidence interval) of the algorithm were 98.9% (96.1%-99.8%), 98.9% (98.3%-99.2%), and 98.9% (98.3%-99.2%), respectively. CONCLUSION(S): The accuracy of the Bayesian algorithm to confirm or rule out EP is excellent. Online Nomogram https://docs.google.com/spreadsheets/d/1jStXlMBjbPyDf6_W0deKGKQLZHU5EFAe8rLhNVPuJuY/edit?usp=sharing.

Prevalence of Chlamydia trachomatis in Women Who Are Candidates for In Vitro Fertilization in a Private Reference Service in Southern Brazil: A Cross-Sectional Study.

Introduction Chlamydia trachomatis (CT) has been related to fallopian tube damage and infertility. Its prevalence in the population that attend public services is known; however, there is scant data on this factor in private infertility clinics. The objective of this study is to verify the prevalence of CT among women attending a private in vitro fertilization (IVF) reference clinic in southern Brazil. Methods This is a cross-sectional study carried out between January 1, 2019, and August 30, 2021, at an IVF private clinic in southern Brazil. Infertile women between 18 and 50 years old, who provided a morning urinary sample for reverse transcription-polymerase chain reaction (RT-PCR) test for CT analysis, were included in the study. The variables studied included the patient's age, body mass index (BMI), duration of infertility, type of infertility, indication for IVF, and detection or not of CT in the urine. Results The prevalence of CT was 10.84% (22 out of 203; 95% CI: 7.27-15.87). Patients with secondary infertility were older and had more ovarian and tubal factors compared to cases of primary infertility. The tubal factor was the most prevalent (27.3% in women with primary infertility and 35.8% in those with secondary). Time of infertility and BMI were similar between groups. Our results are derived from a single private IVF clinic which reduces the external validity. Conclusion The prevalence of 10.84% of CT in this population raises the importance of screening for sexually transmitted infections for proper treatment and to achieve better IVF outcomes.

Are All Views with and without Displacement Maneuver Necessary in Augmentation Mammography? Putting Numbers Into Perspective.

OBJECTIVE: Augmentation implants pose a challenge for radiologists. Displacing the implant allows slightly more breast tissue to be visualized than the standard compression views. The objective of this study was to verify the agreement between craniocaudal (CC) views and CC with implant displacement (CC-ID), mediolateral oblique (MLO) and MLO-ID and the inter- and intraobserver agreement of mammographic images for finding abnormal images. METHODS: The main outcomes [BI-RADS® normal=1,2; abnormal=3,4,5)] were analysed by 3 readers (reader1; reader 2, 1st round, reader 2, 2nd round) in 360 women with breast implants. Comparison between CC/CC-ID and MLO/MLO-ID, and degree of agreement for mammographic images between researchers were made using Kappa index. Proportions were calculated using a 95% confidence interval (95%CI). RESULTS: A total of 87 abnormal findings were identified by reader 2, 2nd round. Abnormal findings were observed in CC-ID=18.8% (68 out of 360; 95%CI=15.1%-23.2%) compared to CC=10.8% (39 out of 360; 95%CI=8%-14.4%, k=0.49); in MLO=10.5% (38 out of 360; 95%CI=7.7%-14.1%) compared to MLO-ID=15.8% (57 out of 360; 95%CI=12.4%-19.9%, k=0.55). The CC-ID was the view that singly identified more abnormal findings (20 out of 87; 23%; 95%CI=15.4% to 32.8%) and the CC was the view that least detected abnormal findings (1 out 87; 95%CI=0.2% to 6.2%). The inter- and intraobserver agreement between readers views was 0.67 and 0.74 respectively. CONCLUSIONS: In women with breast augmentation implants, all views are necessary to identify breast tissue abnormalities. In our sample, the inter- and intraobserver agreement were "substantial".

Lower and extended dosage of misoprostol for cervical ripening in 1st trimester miscarriage (MISO200): A randomized clinical trial.

OBJECTIVE: To compare the efficacy of priming the uterine cervix before Manual Vaccum Aspiration (MVA) using 200 µg or 400 µg of vaginal misoprostol, inserted a mean time of 6 h before MVA in first trimester miscarriage. STUDY DESIGN: Randomized, triple-blind, non-inferiority clinical trial. Patients between 18 and 50 years old, with a diagnosis of miscarriage, were eligible for the study. Patients were allocated to receive either 200 µg or 400 µg of misoprostol before the MVA. The primary outcome was the need to dilate the uterine cervix with mechanical dilators (Hegar dilators). As a secondary outcome, cervical dilatation ≥8 mm before the procedure was considered successful. A difference of <25% was considered as non-inferior. RESULTS: Between December 21, 2016 and October 6, 2019, 269 women were screened. After screening, 105 and 106 women received 200 µg and 400 µg of misoprostol, respectively. Mechanical cervical dilatation was not necessary in 84.8% (95%CI 77% to 90%) and 96.2% (95%CI 91% to 99%), in the 200 µg and 400 µg groups, respectively [difference = 11.5% (95%CI 3.7% to 19.2%). Cervical dilatation of ≥8 mm was 52.4% (95%CI 42.9% to 61.7%) in the 200 µg misoprostol group, while in the 400 µg group was 71.7% (95%CI 62.5% to 79.4%) [difference = 19.3% (95%CI 6.5 to 32.2). CONCLUSION: After a mean time of 6 h, 200 µg of vaginal misoprostol is not inferior to 400 µg of misoprostol for cervical priming before MVA, in first trimester miscarriage. This non-inferiority was not observed when the ≥8 mm criterion was considered.

Comparison of leucine-rich alpha-2-glycoprotein-1 (LRG-1) plasma levels between patients with and without appendicitis, a case-controlled study.

Acute appendicitis (AA) is the first cause of emergency surgery. Leucine-Rich Alpha-2-Glycoprotein 1 (LRG1) has been shown to be a potential biomarker in cases of AA in children, but there are conflicting results for its use in adults. The objective of this study is to compare the median plasma values of LRG1 in patients with acute abdomen with and without appendicitis. This case-control study was conducted prospectively at the emergency room (ER) of a tertiary teaching hospital, between March 1st, 2011 and December 31st, 2012. Patients with recent abdominal pain, aged 18-70 years who attended at the ER were included in the study. Blood samples were drawn at the first presentation. Those who were submitted to surgery and had a pathology report of AA were considered as cases. Those without a need for surgery and treated for other conditions, e.g., pelvic inflammatory disease, were considered as controls. Follow-up in controls was made up to 30 days. LRG1 plasma median values were measured using an ELISA kit and compared between groups. A total of 28 participants, 14 cases with acute appendicitis and 14 controls, were included. The median (range) values of leucine-rich alpha-2-glycoprotein-1 level in the group with appendicitis and control group were 8.8 ng/ml (5.5-31) and 11 (4.6-108) ng/ml, respectively (Mann-Whitney test P = 0.26). Median plasma leucine-rich alpha-2-glycoprotein-1 levels were not useful in diagnosing Acute Appendicitis in patients with acute abdominal pain.

Epidemiological Profile of the Victims of Sexual Violence Treated at a Referral Center in Southern Brazil.

OBJECTIVE: To characterize the sociodemographic profile of women victims of sexual violence treated at a university hospital in southern Brazil. METHOD: The present cross-sectional study included all female victims of sexual violence who attended the sexual violence unit at the Hospital de Clínicas de Porto Alegre (HCPA, in the Portuguese acronym) from April 18, 2000 to December 31, 2017. Data were extracted from the electronic record of the patients and stored in a standardized questionnaire database with epidemiological aspects of the victim, the perpetrators and the type of aggression. Statistical analysis was performed using the chi-squared test for trend and descriptive statistics with 95% confidence interval (CI). RESULTS: During the length of the study, 711 women victims of sexual violence were treated. The mean age of the patients was 24.4 (±10) years old (range from 11 to 69 years old) and most of the victims were white (77.4%), single (75.9%) and sought care at the unit within 72 hours after the occurrence (80.7%). In most cases, violence was exerted by a single perpetrator (87.1%), who was unknown in 67.2% of cases. Victims < 19 years old showed a higher risk of not using contraception (relative risk [RR] = 2.7; 95% CI = 1.9-3.6). CONCLUSION: Most victims of sexual violence were treated within 72 hours of the occurrence. The majority of these victims were white and young, and those < 19 years old had a higher risk of not using contraception and to know the sexual perpetrator.

OBJETIVO: Caracterizar o perfil sociodemográfico de mulheres vítimas de violência sexual atendidas em um hospital universitário da região Sul do Brasil. MéTODOS: Estudo transversal de todas as mulheres atendidas na unidade de vítimas de violência sexual do Hospital de Clínicas de Porto Alegre (HCPA) entre 18 de abril de 2000 a 31 de dezembro de 2017. Os dados foram extraídos a partir do registro eletrônico de um questionário padronizado envolvendo aspectos epidemiológicos da vítima, do agressor e do tipo de agressão. O teste qui-quadrado foi empregado para tendência e estatística descritiva com 95% de intervalo de confiança (IC) foram utilizados para análise estatística. RESULTADOS: Foram atendidas 711 mulheres vítimas de violência sexual. A média da idade das pacientes foi de 24,4 (±10) anos, sendo que a maioria das vítimas era branca (77,4%), solteira (75,9%) e buscou atendimento na unidade dentro de 72 horas após a ocorrência (80,7%). Na maioria dos casos, a violência foi exercida por agressor único (87,1%), sendo este desconhecido em 67,2% dos casos. As vítimas < 19 anos mostraram um maior risco de não estarem usando algum método contraceptivo (risco relativo [RR] = 2,7; IC95% = 1,9­3,6). CONCLUSãO: A maioria das vítimas de violência sexual foi atendida dentro de 72 horas da ocorrência. As vítimas sexuais eram, na sua maioria, brancas e jovens, sendo que as < 19 anos apresentavam um maior risco de não estarem utilizando algum método contraceptivo e de conhecerem o seu agressor.

Antibiotic therapy for pelvic inflammatory disease.

BACKGROUND: Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered intravenously, intramuscularly or orally. We assessed the optimal treatment regimen for PID.  OBJECTIVES: To assess the effectiveness and safety of antibiotic regimens to treat PID. SEARCH METHODS: In January 2020, we searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2020, located through hand and electronic searching; CENTRAL; MEDLINE; Embase; four other databases; and abstracts in selected publications. SELECTION CRITERIA: We included RCTs comparing antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to a comparison of drugs in current use that are recommended by the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the quality of evidence. MAIN RESULTS: We included 39 RCTs (6894 women) in this review, adding two new RCTs at this update. The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision. None of the studies reported quinolones and cephalosporins, or the outcomes laparoscopic evidence of resolution of PID based on physician opinion or fertility outcomes. Length of stay results were insufficiently reported for analysis. Regimens containing azithromycin versus regimens containing doxycycline We are uncertain whether there was a clinically relevant difference between azithromycin and doxycycline in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55; 2 RCTs, 243 women; I2 = 72%; very low-quality evidence). The analyses may result in little or no difference between azithromycin and doxycycline in rates of severe PID (RR 1.00, 95% CI 0.96 to 1.05; 1 RCT, 309 women; low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34; 3 RCTs, 552 women; I2 = 0%; low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin probably improves the rates of cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67; 133 women; moderate-quality evidence), compared to doxycycline.  Regimens containing quinolone versus regimens containing cephalosporin The analysis shows there may be little or no clinically relevant difference between quinolones and cephalosporins in rates of cure for mild-moderate PID (RR 1.05, 95% CI 0.98 to 1.14; 4 RCTs, 772 women; I2 = 15%; low-quality evidence), or severe PID (RR 1.06, 95% CI 0.91 to 1.23; 2 RCTs, 313 women; I2 = 7%; low-quality evidence). We are uncertain whether there was a difference between quinolones and cephalosporins in adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72; 6 RCTs, 1085 women; I2 =  0%; very low-quality evidence). Regimens with nitroimidazole versus regimens without nitroimidazole There was probably little or no difference between regimens with or without nitroimidazoles (metronidazole) in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09; 6 RCTs, 2660 women; I2 = 50%; moderate-quality evidence), or severe PID (RR 0.96, 95% CI 0.92 to 1.01; 11 RCTs, 1383 women; I2 = 0%; moderate-quality evidence). The evidence suggests that there was little to no difference in in adverse effects leading to discontinuation of treatment (RR 1.05, 95% CI 0.69 to 1.61; 17 studies, 4021 women; I2 = 0%; low-quality evidence). . In a sensitivity analysis limited to studies at low risk of bias, there was little or no difference for rates of cure in mild-moderate PID (RR 1.05, 95% CI 1.00 to 1.12; 3 RCTs, 1434 women; I2 = 0%; high-quality evidence). Regimens containing clindamycin plus aminoglycoside versus quinolone We are uncertain whether quinolone have little to no effect in  rates of cure for mild-moderate PID compared to clindamycin plus aminoglycoside (RR 0.88, 95% CI 0.69 to 1.13; 1 RCT, 25 women; very low-quality evidence). The analysis may result in little or no difference between quinolone vs. clindamycin plus aminoglycoside in severe PID (RR 1.02, 95% CI 0.87 to 1.19; 2 studies, 151 women; I2 =  0%; low-quality evidence). We are uncertain whether quinolone reduces adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72; 3 RCTs, 163 women; I2 =  0%; very low-quality evidence). Regimens containing clindamycin plus aminoglycoside versus regimens containing cephalosporin We are uncertain whether clindamycin plus aminoglycoside improves the rates of cure for mild-moderate PID compared to cephalosporin (RR 1.02, 95% CI 0.95 to 1.09; 2 RCTs, 150 women; I2 =  0%; low-quality evidence). There was probably little or no difference in rates of cure in severe PID with clindamycin plus aminoglycoside compared to cephalosporin (RR 1.00, 95% CI 0.95 to 1.06; 10 RCTs, 959 women; I2= 21%; moderate-quality evidence). We are uncertain whether clindamycin plus aminoglycoside reduces adverse effects leading to discontinuation of treatment compared to cephalosporin (RR 0.78, 95% CI 0.18 to 3.42; 10 RCTs, 1172 women; I2 =  0%; very low-quality evidence). AUTHORS' CONCLUSIONS: We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias, a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared to tetracycline (doxycycline).

Simple Trick for Placement of the Robotic Single-Site Device in Obese Patients.

BACKGROUND: The creation of the da Vinci Single-Site© Surgical Platform (DVSSP) allowed robotic surgery to perform single portal procedures. Due to the characteristics of the robotic single-site system, the triangulation of the instruments was optimized, facilitating the execution of the movements. For this, the care in the placement of the portal have fundamental importance. In overweight and patients with obesity, the subcutaneous can impede the ideal positioning of the portal, affecting the movement of the robotic arms and creating discomfort for the surgeon and bringing risks to the patient. TECHNIQUE: Three points are made for subcutaneous reduction, allowing better adaptation of the device. EXPERIENCE: This technique is performed in all patients with obesity submitted to single-site robotic surgery at our service. CONCLUSION: It is a simple, fast, and low-cost method, allowing more safety to patient and comfort for the surgeon.

Unexplained recurrent pregnancy loss and unexplained infertility: twins in disguise.

STUDY QUESTION: Is B-cell CLL/lymphoma 6 (BCL6) endometrial expression, a surrogate biomarker of endometriosis, elevated in women with unexplained recurrent pregnancy loss (uRPL) and unexplained infertility (UI) compared to fertile subjects? SUMMARY ANSWER: Endometrial BCL6 expression is elevated to a similar degree in women with uRPL and UI compared to fertile controls. WHAT IS KNOWN ALREADY: Endometriosis has been linked to the genesis of endometrial progesterone resistance and to specific nuclear proteins, including endometrial BCL6. BCL6 overexpression (immune histologic score > 1.4) has been strongly associated with poor reproductive outcomes in IVF cycles in women with UI. Our previous data have demonstrated an accuracy of 94% for diagnosing endometriosis, and BCL6 protein is elevated in the decidua of women with uRPL. STUDY DESIGN SIZE DURATION: In this case-control study, at a tertiary university teaching hospital, 110 samples (control n = 28; uRPL n = 29; UI n = 53) from pathological archives were analyzed. Timed endometrial biopsies were obtained between 2 January 2002 and 31 December 2016. PARTICIPANTS/MATERIALS SETTING METHOD: LH-timed endometrial biopsies were obtained from women with UI, uRPL (two or more consecutive losses) and normal fertile subjects during the mid-secretory phase of the menstrual cycle. Endometrial BCL6 protein levels were compared in women with UI and uRPL and fertile controls using western blot analysis and immunohistochemistry (HSCORE). MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of the uRPL group was significantly higher than the others [mean (SD)] control = 32.7 (2.6); uRPL = 35.8 (3.7); UI = 32.7 (4.4); P = 0.002, ANOVA]. Seventy-nine percent of women in both subfertile groups (uRPL and UI, 65 out of 82) displayed elevated BCL6 protein levels. From these, a subset of cases with abnormal BCL6 went to laparoscopy and endometriosis was found in 9 out of 11 cases of uRPL and in 20 out of 21 cases of UI. Median BCL6 HSCORE for controls versus uRPL and UI was significantly different [median (interquartile); control = 0.3 (0.02 to 0.5); uRPL = 3 (1.9 to 3.6); UI = 2.9 (1.6 to 3.1); P < 0.0001, Kruskal-Wallis]. A significant trend in the association between the degree of infertility (fertile, uRPL and UI) and the HSCORE level (negative, medium and high) was found (P < 0.001; x 2 for trend). Western blot of representative samples from each group demonstrated similar findings based on protein levels in the whole endometrium. After running ANCOVA analysis for age difference, the BCL6 difference among groups was still significant (P-value < 0.0001). LIMITATIONS REASONS FOR CAUTION: We studied subjects with two consecutive pregnancy losses rather than the definition adopted in Europe of three losses. The findings may lack external validity in other clinical settings (e.g. low prevalence of endometriosis). WIDER IMPLICATIONS OF THE FINDINGS: Based on the data presented here, we postulate that the degree of BCL6 expression may represent a continuum of progesterone resistance and response to inflammation that occurs in women with endometriosis, yielding different degrees of infertility, from uRPL to UI. STUDY FUNDING/COMPETING INTERESTS: This study was supported by NICHD/NIH R01 HD067721 (SLY and BAL), by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: Grant 99999.003035/2015-08 (BAL) and by CAPES/PROAP (RFS). Two authors (BAL, SLY) have licensed intellectual property for the detection of endometriosis. Dr Bruce Lessey is an unpaid scientific Advisor for CiceroDx. The other authors report no conflict of interest.

Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression.

PURPOSE: To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic. METHODS: All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group. RESULTS: Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group. CONCLUSIONS: Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management.

Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID). DESIGN: This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. DATA SOURCES: Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature. ELIGIBILITY CRITERIA: RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. RESULTS: We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed. CONCLUSIONS: We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.

IL-17 blood levels increase in healthy pregnancy but not in spontaneous abortion.

Cytokines are essential to maintain and coordinate the correct activity of immune cells during human pregnancy. IL-17 is a pro-inflammatory cytokine that induces the expression of many inflammatory mediators. The aim of this study was to compare the levels of Th1, Th2 and Th17 cytokines of women ongoing normal pregnancy with those found in women who suffered spontaneous abortion. IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ peripheral blood levels were measured in women who suffered spontaneous abortion (n = 13, blood collected up to 24 h after abortion), and were compared with healthy successful pregnancies (n = 16). Cytokine levels were measured using a cytometric bead array (CBA analysis). Similar cytokine levels were observed between spontaneous abortion and healthy pregnant women excepted to IL-17, which levels were increased in the healthy pregnant women (p = 0.0232). Our results show high IL-17 levels in the peripheral blood of women at late stages of healthy pregnancy, although low IL-17 levels were detected in the peripheral blood of women just after spontaneous abortion. In line with recent studies, this finding highlights IL-17 as a regulatory cytokine essential to the maintenance of a successful pregnancy.

Which mode and potency of electrocoagulation yields the Smallest Unobstructed Area of the Fallopian Tubes? / Qual modo e potência produzem a menor área de nãoobstrução nas tubas de Falópio?

Abstract Objective To determine which mode and potency of electrocoagulation, using a modern electrosurgical generator, yields the smallest unobstructed area of the Fallopian tubes. Methods In an experimental study, tubes from 48 hysterectomies or tubal ligation were evaluated. Tubes were randomly allocated to one of the following groups: group A) 25 W x 5 seconds (n = 17); group B) 30 W x 5 seconds (n = 17); group C) 35 W x 5 seconds (n = 18), group D) 40 W x 5 seconds (n = 20); group E) 40 W x 5 seconds with visual inspection (blanch, swells, collapse) (n = 16); group F) 50 W x 5 seconds (n = 8). Bipolar electrocoagulation was performed in groups A to E, and monopolar electrocoagulation was performed in group F. Coagulation mode was used in all groups. Digital photomicrography of the transversal histological sections of the isthmic segment of the Fallopian tube were taken, and themedian percentage of unobstructed luminal area (mm2) was measured with ImageJ software (ImageJ, National Institutes of Health, Bethesda, MD, USA). The Kruskal-Wallis test or analysis of variance (ANOVA) was used for statistical analysis. Results Ninety-six Fallopian tube sections were analyzed. The smallest median occluded area (%; range) of the Fallopian tube was obtained in the group with 40 W with visual inspection (8.3%; 0.9-40%), followed by the groups 25 W (9.1%; 0-35.9%), 40 W (14.2; 0.9-43.2%), 30 W (14.2; 0.9-49.7%), 35 W (15.1; 3-46.4%) and 50 W (38.2; 3.1-51%). No statistically significant difference was found among groups (p = 0.09, Kruskal-Wallis test). Conclusion The smallest unobstructed area was obtained with power setting at 40 W with visual inspection using a modern electrosurgical generator. However, no statistically significant difference in the unobstructed area was observed among the groups using these different modes and potencies.

Resumo Objetivo Determinar em qual modo e potência, usando unidades geradoras modernas de eletrocoagulação, produz a menor área de não-obstrução das tubas de Falópio. Métodos Num estudo experimental, tubas uterinas derivadas de 48 histerectomias ou ligadura tubária foram avaliadas. As tubas foram alocadas aleatoriamente para um dos seguintes grupos: grupo A) 25 W x 5 segundos (n = 17); grupo B) 30 W x 5 segundos (n = 17); grupo C) 35 Wx 5 segundos (n = 18), grupo D) 40 W, 5 segundos (n = 20); grupo E) 40 W x 5 segundos inspeção visual (branqueia, incha e colapsa) (n = 16); grupo F) 50 Wx 5 segundos (n = 8). A eletrocoagulação bipolar foi usada nos grupos de A a E, e a eletrocoagulação monopolar, no grupo F. O modo de coagulação foi utilizado em todos os grupos. Cortes histológicos transversais do segmento ístmico das tubas de Falópio foram corados e fotografados digitalmente, e a percentagem da área luminal (mm2) não-obstruída foi medida com o software ImageJ (ImageJ, National Institutes of Health, Bethesda, MD, USA). O teste de Kruskal-Wallis ou ANOVA foram usados para a análise estatística. Resultados Noventa e seis cortes histológicos de tubas de Falópio foram analisados. A mediana da menor área não-obstruída (%; amplitude) da tuba de Falópio foi obtida no grupo 40 W com inspeção visual (8,3%; 0,9-40%), seguido do grupo 25 W (9,1%; 0- 35,9%), 40W(14,2; 0,9-43,2%), 30 W(14.2; 0,9-49,7%), 35 W(15,1; 3-46,4%) e 50 W (38,2; 3.1-51%). Não houve diferença significativa entre os grupos (p = 0,09, teste de Kruskal-Wallis). Conclusão A menor área não-obstruída foi obtida com a potência de 40 W com inspeção visual usando um gerador moderno de eletrocirurgia. Contudo, nenhuma diferença significativa na área não-obstruída foi observada entre os grupos usando esses modos e potências.

Which mode and potency of electrocoagulation yields the Smallest Unobstructed Area of the Fallopian Tubes?

OBJECTIVE: To determine which mode and potency of electrocoagulation, using a modern electrosurgical generator, yields the smallest unobstructed area of the Fallopian tubes. METHODS: In an experimental study, tubes from 48 hysterectomies or tubal ligation were evaluated. Tubes were randomly allocated to one of the following groups: group A) 25 W x 5 seconds (n = 17); group B) 30 W x 5 seconds (n = 17); group C) 35 W x 5 seconds (n = 18), group D) 40 W x 5 seconds (n = 20); group E) 40 W x 5 seconds with visual inspection (blanch, swells, collapse) (n = 16); group F) 50 W x 5 seconds (n = 8). Bipolar electrocoagulation was performed in groups A to E, and monopolar electrocoagulation was performed in group F. Coagulation mode was used in all groups. Digital photomicrography of the transversal histological sections of the isthmic segment of the Fallopian tube were taken, and the median percentage of unobstructed luminal area (mm2) was measured with ImageJ software (ImageJ, National Institutes of Health, Bethesda, MD, USA). The Kruskal-Wallis test or analysis of variance (ANOVA) was used for statistical analysis. RESULTS: Ninety-six Fallopian tube sections were analyzed. The smallest median occluded area (%; range) of the Fallopian tube was obtained in the group with 40 W with visual inspection (8.3%; 0.9-40%), followed by the groups 25 W (9.1%; 0-35.9%), 40 W (14.2; 0.9-43.2%), 30 W (14.2; 0.9-49.7%), 35 W (15.1; 3-46.4%) and 50 W (38.2; 3.1-51%). No statistically significant difference was found among groups (p = 0.09, Kruskal-Wallis test). CONCLUSION: The smallest unobstructed area was obtained with power setting at 40 W with visual inspection using a modern electrosurgical generator. However, no statistically significant difference in the unobstructed area was observed among the groups using these different modes and potencies.

OBJETIVO: Determinar em qual modo e potência, usando unidades geradoras modernas de eletrocoagulação, produz a menor área de não-obstrução das tubas de Falópio. MéTODOS: Num estudo experimental, tubas uterinas derivadas de 48 histerectomias ou ligadura tubária foram avaliadas. As tubas foram alocadas aleatoriamente para um dos seguintes grupos: grupo A) 25 W x 5 segundos (n = 17); grupo B) 30 W x 5 segundos (n = 17); grupo C) 35 W x 5 segundos (n = 18), grupo D) 40 W, 5 segundos (n = 20); grupo E) 40 W x 5 segundos inspeção visual (branqueia, incha e colapsa) (n = 16); grupo F) 50 W x 5 segundos (n = 8). A eletrocoagulação bipolar foi usada nos grupos de A a E, e a eletrocoagulação monopolar, no grupo F. O modo de coagulação foi utilizado em todos os grupos. Cortes histológicos transversais do segmento ístmico das tubas de Falópio foram corados e fotografados digitalmente, e a percentagem da área luminal (mm2) não-obstruída foi medida com o software ImageJ (ImageJ, National Institutes of Health, Bethesda, MD, USA). O teste de Kruskal-Wallis ou ANOVA foram usados para a análise estatística. RESULTADOS: Noventa e seis cortes histológicos de tubas de Falópio foram analisados. A mediana da menor área não-obstruída (%; amplitude) da tuba de Falópio foi obtida no grupo 40 W com inspeção visual (8,3%; 0,9­40%), seguido do grupo 25 W (9,1%; 0­35,9%), 40W (14,2; 0,9­43,2%), 30 W (14.2; 0,9­49,7%), 35 W (15,1; 3­46,4%) e 50 W (38,2; 3.1­51%). Não houve diferença significativa entre os grupos (p = 0,09, teste de Kruskal-Wallis). CONCLUSãO: A menor área não-obstruída foi obtida com a potência de 40 W com inspeção visual usando um gerador moderno de eletrocirurgia. Contudo, nenhuma diferença significativa na área não-obstruída foi observada entre os grupos usando esses modos e potências.