Molecular dynamics identifies semi-rigid domains in the PD-1 checkpoint receptor bound to its natural ligand PD-L1.

Cells in danger of being erroneously attacked by leucocytes express PD-L1 on their surface. These cells activate PD-1 on attacking leucocytes and send them to death, thus curbing erroneous, autoimmune attack. Unfortunately, cancer cells exploit this mechanism: By expressing PD-L1, they guard themselves against leucocyte attack and thereby evade immune clearance.

Sexual Function in Postmenopausal Women With Symptomatic Pelvic Organ Prolapse Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial.

Background: Local estrogen therapy (LET) has beneficial effects on genitourinary atrophy; however it is currently unclear if LET improves sexual function in postmenopausal women with pelvic organ prolapse (POP).

Aim: To evaluate if LET vs placebo results in an improved sexual function in postmenopausal women with symptomatic POP.

Methods: We performed a secondary analysis of sexual outcomes of a previous randomized controlled trial comparing LET and placebo in 120 postmenopausal women (60/group) with symptomatic POP stage ≥3 and planned prolapse surgery.

Decision Theory versus Conventional Statistics for Personalized Therapy of Breast Cancer.

Estrogen and progesterone receptors being present or not represents one of the most important biomarkers for therapy selection in breast cancer patients. Conventional measurement by immunohistochemistry (IHC) involves errors, and numerous attempts have been made to increase precision by additional information from gene expression. This raises the question of how to fuse information, in particular, if there is disagreement.

Temporal trends in obstetric anal sphincter injury from the first vaginal delivery in Austria, Canada, Norway, and Sweden.

Introduction: Obstetric anal sphincter injuries (OASI) are severe complications that can cause considerable short- and long-term morbidity. Austria, Canada, Norway, and Sweden have similar socio-economic characteristics, and all four countries have access to national birth registers. In this study, we hypothesized that the incidence of OASI should be very similar for different obstetric scenarios in these four countries.

Wide Variation in Post-Void Residual Management after Urogynecologic Surgery: A Survey of Urogynecologists' Practices.

To date there is no standardized regimen or evidence-based practical guideline concerning post-void residual (PVR) measurement after urogynecologic surgeries. This survey aimed to evaluate current practice patterns and the approach taken among urogynecologists surrounding PVR measurement. An online survey was sent to members of several urogynecologic societies assessing pre- and postoperative management of patients undergoing urogynecologic surgery.

Clinical risk factors for recurrence of pelvic organ prolapse after primary native tissue prolapse repair.

Objective: To define potential risk factors for recurrence of prolapse.

Methods: This short report included all women who presented with recurrence of prolapse as well as without any recurrence signs after a vaginal approach of native tissue prolapse repair at an urogynecological center in Austria.

Results: A total of 124 recurrence cases and 64 women with no signs of recurrence after their index prolapse surgery were included.

Decision theory for precision therapy of breast cancer.

Correctly estimating the hormone receptor status for estrogen (ER) and progesterone (PGR) is crucial for precision therapy of breast cancer. It is known that conventional diagnostics (immunohistochemistry, IHC) yields a significant rate of wrongly diagnosed receptor status. Here we demonstrate how Dempster Shafer decision Theory (DST) enhances diagnostic precision by adding information from gene expression.

Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial.

Purpose: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT.

Patients And Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT.

Pembrolizumab Induces an Unexpected Conformational Change in the CC'-loop of PD-1.

To improve cancer immunotherapy, a clearer understanding of key targets such as the immune checkpoint receptor PD-1 is essential. The PD-1 inhibitors nivolumab and pembrolizumab were recently approved by the FDA. The CC'-loop of PD-1 has been identified as a hotspot for drug targeting.

Multicriteria Decision Analysis Applied to the Clinical Use of Pharmacotherapy for Overactive Bladder Symptom Complex.

Context: The nonspecific storage symptom complex overactive bladder (OAB) is an important clinical condition in functional urology. Until recently, pharmacological therapy comprised antimuscarinic drugs, but more recently beta 3 agonists have added to the available agents. Traditional reporting of efficacy and safety of these agents relies upon regulatory placebo-controlled studies.

The value of pretreatment serum butyrylcholinesterase level as a novel prognostic biomarker in patients with cervical cancer treated with primary (chemo-)radiation therapy.

Background: Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy.

Methods: We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015.

Genetic association in female stress urinary incontinence based on proteomic findings: a case-control study.

Introduction And Hypothesis: Previous studies have indicated a hereditary component of stress urinary incontinence; however, evidence on candidate genes or single-nucleotide polymorphisms (SNPs) is scarce. We hypothesize a genetic association of female stress urinary incontinence based on significant differences of the urinary and serum proteomic pattern in the identical study population.

Methods: Case-control study of 19 patients and 19 controls.

Prolapse surgery versus vaginal pessary in women with symptomatic pelvic organ prolapse: which factors influence the choice of treatment?

Objective: To investigate which specific clinical factors influence patients' choice of prolapse treatment.

Methods: This study includes a total of 510 cases with symptomatic pelvic organ prolapse (POP) of stage II or higher requiring prolapse treatment. Patients were divided into surgery and pessary groups according to their own choice and treatment preference.

Association of uterine leiomyoma and overactive bladder syndrome.

Objective: To assess associations between anterior and/or fundal uterine leiomyoma and overactive bladder syndrome.

Methods: The present cohort study recruited women diagnosed with fundal/anterior uterine leiomyoma by standardized transvaginal ultrasonography at the Medical University of Vienna, Austria, between January 1, 2010, and December 31, 2013, in addition to an age-matched control group of women without uterine leiomyoma. The International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB) was mailed to all eligible participants.

AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer - a retrospective multi-centre study.

Background: AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC).

Methods: AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC.

Serum proteomic pattern in female stress urinary incontinence.

The pathophysiology of Stress Urinary Incontinence (SUI) is poorly understood. The aim of this study was to identify the serum proteomic profile in patients with SUI and to replicate findings from a preceding study in which a significant difference in the urinary proteome was identified. Serum samples were collected from 38 patients (19 SUI; 19 matched, continent controls).

Association of endogenous circulating sex steroids and condition-specific quality of life domains in postmenopausal women with pelvic floor disorders.

Objective: To examine the relationship between endogenous sex steroids and various condition-specific quality of life domains in postmenopausal women with pelvic floor disorders. We hypothesized that woman with lowest androgen and estradiol concentrations would report worse scores of quality of life domains.

Methods: Forty-six women with pelvic organ prolapse (POP) and 47 cases with stress urinary incontinence (SUI) answered the validated pelvic floor questionnaire and underwent serum sex steroid measurement.

Gene expression information improves reliability of receptor status in breast cancer patients.

Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements.

Role of serum steroid hormones in women with stress urinary incontinence: a case-control study.

Objectives: To investigate the potential relationship between endogenous sex steroids and presence of stress urinary incontinence (SUI).

Patients And Methods: A total of 47 peri- and postmenopausal women with SUI were matched 1:1 with 47 continent women based on age, menopausal status, body mass index (BMI) and parity. Blood samples were drawn from all the women for assessment of oestradiol (E2), follicle-stimulating hormone, luteinizing hormone, testosterone, androstendion (AEON), dehydroepiandrosterone sulphate and sex hormone-binding globulin with an electrochemiluminescence immunoassay.

Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence.

Context: Surgical nonautologous meshes have been used for several decades to repair abdominal wall herniae. Implantable materials have been adopted for the treatment of female and male stress urinary incontinence (SUI) and female pelvic organ prolapse (POP).

Objective: A consensus review of existing data based on published meta-analyses and reviews.

Management of vesicovaginal fistulas (VVFs) in women following benign gynaecologic surgery: A systematic review and meta-analysis.

Background: Vesicovaginal fistulas (VVF) are the most commonly acquired fistulas of the urinary tract, but we lack a standardized algorithm for their management. Surgery is the most commonly preferred approach to treat women with primary VVF following benign gynaecologic surgery.

Objective: To carry out a systematic review and meta-analysis on the effectiveness of operative techniques or conservative treatment for patients with postsurgical VVF.

The Impact of the Duration of Adjuvant Chemotherapy on Survival in Patients with Epithelial Ovarian Cancer - A Retrospective Study.

Objective: The aim of the present study was to investigate the prognostic role of the duration of adjuvant chemotherapy in patients with epithelial ovarian, fallopian tube and primary peritoneal cancer (EOC).

Materials And Methods: Within the present study we retrospectively evaluated the data of 165 consecutive patients with EOC treated with primary surgery followed by six completed cycles of platinum-taxan based intravenous adjuvant chemotherapy. Medians of total duration of chemotherapy were compared with clinical-pathological parameters.