Towards clinical adherence monitoring of oral endocrine breast cancer therapies by LC-HRMS-method development, validation, comparison of four sample matrices, and proof of concept.

Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations.

Dual Sec62/Ki67 immunocytochemistry of liquid-based cytological preparations represents a highly valid biomarker for non-invasive detection of head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid-based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non-invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions. METHODS: 104 HNSCC patients and 28 control patients, including healthy patients (n = 17), papilloma (n = 1) and leukoplakia patients (n = 10), were included in this study. For all patients, an LBC swab followed by simultaneous immunocytochemical detection of Sec62 and Ki67 was performed. Immunocytochemical as well as cytopathological results were correlated with histological diagnoses and clinical findings. RESULTS: All HNSCC patients (100%) showed dual Sec62/Ki67 positivity, and all control patients except for the papilloma patient were negative for Sec62/Ki67 (96.4%), resulting in a 100% sensitivity and 96.4% specificity of Sec62/Ki67 dual stain for non-invasive detection of HNSCC. The positive predictive value was 99% and the negative predictive value was 100%. Sec62 expression levels showed a positive correlation with tumour de-differentiation (p = 0.0489). CONCLUSION: Simultaneous immunocytochemical detection of Sec62/Ki67 using LBC represents a promising non-invasive and easy-to-apply tool for the early detection of HNSCC in routine clinical practice. This novel technique can help to avoid incisional biopsies and reduce the frequency with which general anaesthesia is used in diagnostic procedures in patients with suspicious oral lesions.

Will I soon be out of my job? Quality and guideline conformity of ChatGPT therapy suggestions to patient inquiries with gynecologic symptoms in a palliative setting.

PURPOSE: The market and application possibilities for artificial intelligence are currently growing at high speed and are increasingly finding their way into gynecology. While the medical side is highly represented in the current literature, the patient's perspective is still lagging behind. Therefore, the aim of this study was to evaluate the recommendations of ChatGPT regarding patient inquiries about the possible therapy of gynecological leading symptoms in a palliative situation by experts. METHODS: Case vignettes were constructed for 10 common concomitant symptoms in gynecologic oncology tumors in a palliative setting, and patient queries regarding therapy of these symptoms were generated as prompts for ChatGPT. Five experts in palliative care and gynecologic oncology evaluated the responses with respect to guideline adherence and applicability and identified advantages and disadvantages. RESULTS: The overall rating of ChatGPT responses averaged 4.1 (5 = strongly agree; 1 = strongly disagree). The experts saw an average guideline conformity of the therapy recommendations with a value of 4.0. ChatGPT sometimes omits relevant therapies and does not provide an individual assessment of the suggested therapies, but does indicate that a physician consultation is additionally necessary. CONCLUSIONS: Language models, such as ChatGPT, can provide valid and largely guideline-compliant therapy recommendations in their freely available and thus in principle accessible version for our patients. For a complete therapy recommendation, an evaluation of the therapies, their individual adjustment as well as a filtering of possible wrong recommendations, a medical expert's opinion remains indispensable.

Diagnostic performance of additional imaging tests for staging purposes in a bicentric German series of low-risk early breast cancer patients.

PURPOSE: Low-risk early breast cancer rarely leads to the development of metastatic disease, and in these patients, additional imaging test is controversial. The aim of our study was to evaluate the conventional staging procedures in a bicentric German series of low-risk breast carcinoma patients. METHODS: Retrospective evaluation of all patients diagnosed with early, low-risk breast cancer at Saarland University Hospital and Freiburg University Hospital in 2017 was performed. Clinical patient characteristics, the number and type of additional imaging examinations, follow-up examinations, and results were evaluated. The detection rate of metastases and the rate of false-positive findings were analyzed. RESULTS: A total of 203 patients were included, with all patients received at least one additional imaging test. Initially, a total of 562 additional imaging examinations were performed: 166 chest X-rays, 169 upper abdominal ultrasounds, 199 bone scans, 27 computer tomographies (CT) chest and abdomen, and 1 CT abdomen. 6.8% of patients had abnormal findings reported, requiring 38 additional imaging examinations. One patient (0.5%) was found to have bone metastases. The rate of false-positive findings in the performed additional imaging procedures was 6.6%. CONCLUSION: Metastatic disease was detected in one of 203 patients with low-risk early breast cancer. A total of 562 examinations and additional 38 follow-up examinations were performed without detection of metastasis (this corresponds to approximately 3 examinations/patient). The rate of false-positive findings was 6.6%. The performance of additional imaging procedures for detection of distant metastases should be critically reconsidered in patients with low-risk early breast cancer.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Objective structured assessment of medical students' technical skills in second-degree perineal laceration repair with sponge model-based training.

PURPOSE: In this cohort study, we used a sponge simulator to train students in second-degree perineal laceration repair. We examined whether the training course improved the students' skills, as measured with an objective structured assessment of technical skills (OSATS) and by a senior physician. We also examined the correlation between these ratings to assess the validity of OSATS application in this context. METHODS: Between April and July 2022, 40 medical students took part in gynecological/obstetrics training that included a lecture about perineal trauma and the viewing of a video that demonstrated second-degree perineal laceration repair using a sponge model. They then underwent initial evaluation by a senior physician and OSATS application, yielding two independent scores. After training with the sponge model, a second evaluation was performed. The OSATS assessed practical skills (8 items) and suture results (2 items). The senior physician assigned ratings on a five-point ordinal scale ranging from 1 (excellent) to 5 (poor). RESULTS: Training with the sponge simulator significantly increased students' OSATS (practical skills, p < 0.001; suture results, p < 0.05) and senior physician (p < 0.001) ratings. The OSATS and senior physician ratings correlated strongly (Spearman's r: first assessment, - 0.72; second assessment, - 0.74; p < 0.01). CONCLUSION: The sponge-based training improves students' skills for the repair of a second-degree perineal laceration. The OSATS for the sponge model might be a valid option to examine medical students in an obstetrical course.

Sonographic features of adenomyosis correlated with clinical symptoms and intraoperative findings: a case-control study.

PURPOSE: Adenomyosis is a common disease of females during their reproductive age. As of today, histologic examination of the uterus after hysterectomy constitutes the gold standard for diagnosis. The aim of this study was to determine the validity of sonographic, hysteroscopic, and laparoscopic criteria for the diagnosis of the disease. METHODS: This study included data collected from 50 women in the reproductive age of 18-45 years, who underwent a laparoscopic hysterectomy in the gynecology department of the Saarland University Hospital in Homburg between 2017 and 2018. The patients with adenomyosis were compared with a healthy control group. RESULTS: We collected data of anamnesis, sonographic criteria, hysteroscopic criteria and laparoscopic criteria and compared it with the postoperative histological results. A total 25 patients were diagnosed with adenomyosis postoperatively. For each of these; at least three sonographic diagnostical criteria for adenomyosis were found compared with a maximum of two for the control group. CONCLUSION: This study demonstrated an association between pre- and intraoperative signs of adenomyosis. In this way, it shows a high diagnostic accuracy of the sonographic examination as a pre-operative diagnostic method of the adenomyosis.

Sex Differences in the Frequencies of B and T Cell Subpopulations of Human Cord Blood.

Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether the sex of the newborn affects the lymphocyte subpopulations in the cord blood. Nine B and twenty-one T cell subpopulations were characterized using flow cytometry in human cord blood from sixteen male and twenty-one female newborns, respectively. Except for transitional B cells and naïve B cells, frequencies of B cell counts across all subsets was higher in the cord blood of male newborns than in female newborns. The frequency of naïve thymus-negative Th cells was significantly higher in male cord blood, whereas the remaining T cell subpopulations showed a higher count in the cord blood of female newborns. Our study is the first revealing sex differences in the B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system, urging the need to expand research in this area.

The 3q Oncogene SEC62 Predicts Response to Neoadjuvant Chemotherapy and Regulates Tumor Cell Migration in Triple Negative Breast Cancer.

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.

Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and its prognostic impact resulted in a hazard ratio (HR) of 1.89 (Simulatedaggressive vs SimulatedindolentP < .001), similar to patients with actual CTCs enumeration (HR 2.76; P < .001). The classifier's performance was then tested on an independent retrospective database comprising 446 consecutive hormone receptor (HR)-positive HER2-negative MBC patients. The model further stratified clinical subgroups usually considered prognostically homogeneous such as patients with bone-only or liver metastases. Bone-only disease classified as Simulatedaggressive had a significantly worse overall survival (OS; P < .0001), while patients with liver metastases classified as Simulatedindolent had a significantly better prognosis (P < .0001). Consistent results were observed for patients who had undergone CTCs enumeration in the pooled population. The differential prognostic impact of endocrine- (ET) and chemotherapy (CT) was explored across the simulated subgroups. No significant differences were observed between ET and CT in the overall population, both in terms of progression-free survival (PFS) and OS. In contrast, a statistically significant difference, favoring CT over ET was observed among Simulatedaggressive patients (HR: 0.62; P = .030 and HR: 0.60; P = .037, respectively, for PFS and OS).

Preoperative Sonographic Prediction of Limited Axillary Disease in Patients with Primary Breast Cancer Meeting the Z0011 Criteria: an Alternative to Sentinel Node Biopsy?

PURPOSE: To assess the accuracy of preoperative sonographic staging for prediction of limited axillary disease (LAD, one or two metastatic lymph nodes) and to identify factors associated with high prediction-pathology concordance in patients with early-stage breast cancer meeting the Z0011 criteria. MATERIALS AND METHODS: Patients treated between January 2015 and January 2020 were included in this retrospective, multicentric analysis of prospectively acquired service databases. The accuracy of LAD prediction was assessed separately for patients with one and two suspicious lymph nodes on preoperative sonography. Test validity outcomes for LAD prediction were calculated for both groups, and a multivariate model was used to identify factors associated with high accuracy of LAD prediction. RESULTS: Of 2059 enrolled patients, 1513 underwent sentinel node biopsy, 436 primary and 110 secondary axillary dissection. For LAD prediction in patients with one suspicious lymph node on preoperative ultrasound, sensitivity was 92% (95% CI 87-95%), negative predictive value (NPV) was 92% (95% CI 87-95%), and the false-negative rate (FNR) was 8% (95% CI 5-13%). For patients with two preoperatively suspicious nodes, the sensitivity, NPV, and FNR were 89% (95% CI 84-93%), 73% (62-83%), and 11% (95% CI 7-16%), respectively. On multivariate analysis, the number of suspicious lymph nodes was associated inversely with correct LAD prediction ([OR 0.01 (95% CI 0.01-0.93), p ≤ 0.01]. CONCLUSIONS: Sonographic axillary staging in patients with one metastatic lymph node predicted by preoperative ultrasound showed high accuracy and a false-negative rate comparable to sentinel node biopsy for prediction of limited axillary disease.

Immunohistochemical assessment of PD-L1 expression using three different monoclonal antibodies in triple negative breast cancer patients.

BACKGROUND: PD-L1 receptor expression in breast cancer tissue can be assessed with different anti-human PD-L1 monoclonal antibodies. The performance of three specific monoclonal antibodies in a head-to-head comparison is unknown. In addition, a potential correlation of PD-L1 expression and clinico-pathological parameters has not been investigated. METHODS: This was a retrospective study on tissue samples of patients with histologically confirmed triple negative breast cancer (TNBC). PD-L1 receptors were immune histochemically stained with three anti-human PD-L1 monoclonal antibodies: 22C3 and 28-8 for staining of tumor cell membranes (TC) and cytoplasm (Cyt), SP142 for immune cell staining (IC). Three different tissue samples of each patient were evaluated separately by two observers in a blinded fashion. The percentage of PD-L1 positive tumor cells in relation to the total number of tumor cells was determined. For antibodies 22C3 and 28-8 PD-L1 staining of 0 to < 1% of tumor cells was rated "negative", 1-50% was rated "positive" and > 50% was rated "strong positive". Cyt staining was defined as "negative" when no signal was observed and as "positive", when any positive signal was observed. For IC staining with SP142 all samples with PD-L1 expression ≥ 1% were rated as "positive". Finally, the relationship between PD-L1 expression and clinico-pathological parameters was analyzed. RESULTS: Tissue samples from 59 of 60 enrolled patients could be analyzed. Mean age was 55 years. Both the monoclonal antibodies 22C3 and 28-8 had similar properties, and were positive for both TC in 13 patients (22%) and for Cyt staining in 24 patients (40.7%). IC staining with antibody SP142 was positive in 24 patients (40.7%), who were also positive for Cyt staining. The differences between TC and Cyt staining and TC and IC staining were significant (p = 0.001). Cases with positive TC staining showed higher Ki67 expression compared to those with negative staining, 40 vs 30%, respectively (p = 0.05). None of the other clinico-pathological parameters showed any correlation with PDL1 expression. CONCLUSIONS: Antibodies 22C3 and 28-8 can be used interchangeably for PD-L1 determination in tumor cells of TNBC patients. Results for Cyt staining with 22C3 or 28-8 and IC staining with SP142 were identical. In our study PD-L1 expression correlates with Ki67 expression but not with OS or DFS.

Acute Sheehan's syndrome manifesting initially with diabetes insipidus postpartum: a case report and systematic literature review.

PURPOSE: Acute Sheehan's syndrome is a rare, but potentially life-threatening, obstetric event that can be complicated by diabetes insipidus. Little information on the diagnosis and treatment of Sheehan's syndrome with diabetes insipidus is available. We report on a 28-year-old patient who developed acute Sheehan's syndrome with diabetes insipidus after giving birth, and on a systematic review of similar cases. METHODS: We performed a systematic review of the literature cataloged in PubMed and Google Scholar using the keywords "Sheehan syndrome" OR "Sheehan's syndrome" AND "diabetes insipidus" to identify relevant case reports published between 1990 and 2021. Eight Reports met the inclusion criteria (English-language abstracts available, onset in the puerperium, information about the day of the onset). RESULTS: In the present case, postpartum curettage was necessary to remove the residual placenta. The total amount of blood loss was severe (2500 ml). On the second day postpartal, the patient developed polyuria. Laboratory analysis revealed hypernatremia with increased serum osmolality and decreased urinary osmolality. Hormone analysis showed partial hypopituitarism involving the thyroid, corticotropic, and gonadotropic axes. The prolactin level was elevated. Brain magnetic resonance imaging showed pituitary gland infarction. Desmopressin therapy was initiated and resolved the polyuria. Hormone replacement therapy was administered. Four months later, the patient was well, with partial diabetes insipidus. The literature review indicated that this case was typical in terms of symptoms and disease onset. Most reported cases involve hypotension and peripartum hemorrhage, but some patients without hemorrhage also develop Sheehan's syndrome. Elevated prolactin levels are uncommon and associated with poor prognosis in patients with Sheehan's syndrome. CONCLUSION: Acute Sheehan's syndrome with diabetes insipidus involves nearly all pituitary hormone axes, indicating severe disease. Prolactin elevation could suggest that a case of Sheehan's syndrome is severe.

Cytology-based Cancer Surgery of the Head and Neck (CyCaS-HN): a prospective, randomized, controlled clinical trial.

PURPOSE: Liquid-based cytology (LBC) is routinely used in gynecology but is rarely applied in head and neck oncology though many suspicious lesions are easily accessible. While several studies have evaluated the potential use of LBC for early detection and molecular characterization of head and neck squamous cell carcinomas (HNSCCs), no study investigated its potential role in surgical management and therapy planning so far. METHODS: Twenty-five patients with cT1-2 squamous cell carcinomas of the oral cavity and oropharynx were prospectively enrolled in this study and were randomized to two treatment arms: in the control arm, a diagnostic panendoscopy with incisional biopsy was followed by a second operation with transoral tumor resection ± neck dissection and tracheostomy. In the intervention arm, patients underwent LBC diagnostics and in case of a positive result received one single operation with panendoscopy and incisional biopsy for confirmation of LBC result by rapid section histology followed by transoral tumor resection ± neck dissection and tracheostomy in the same session. RESULTS: Time between clinical diagnosis and definitive surgical treatment was significantly shorter in the intervention group compared with the control group (p < 0.0001). Additionally, time of hospitalization (p < 0.0001) and cumulative operation time (p = 0.062) were shorter in the intervention group. No significant differences in overall, progression-free, and disease-specific survival were observed. CONCLUSION: Cytology-based cancer surgery is a promising therapeutic strategy that can potentially be considered for a well-defined group of early-stage HNSCC patients and help to avoid repetitive general anesthesia, shorten the diagnosis-to-treatment interval and spare operation as well as hospitalization time.

Psychometric properties of the German-language questionnaire for urinary incontinence diagnosis (QUID) in women with urinary incontinence.

PURPOSE: The aim of this study was to translate the questionnaire for urinary incontinence diagnosis (QUID) into German and to assess its psychometric properties in German-speaking women with urinary incontinence (UI). The QUID contains two subscales to measure symptom severity of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) and to distinguish between both forms. METHODS: A total of 161 women with UI completed the QUID and the King's Health Questionnaire (KHQ), each in the German version. To examine construct validity Spearman's correlation coefficients between both questionnaires were computed. Furthermore, the internal consistency (Cronbach's alpha) of the QUID and its criterion validity were examined. Looking at criterion validity, sensitivity, specificity, ROC curves, and Youden-indexes were computed for both subscales. RESULTS: The QUID showed good construct validity by strong correlations with related domains of the KHQ. Cronbach's alpha values were good for both subscales of the QUID (SUI-subscale: 0.76; UUI-subscale: 0.86). Sensitivity and specificity were 83% (95% CI, 0.72-0.9) and 45% (95% CI, 0.25-0.67) for the SUI-subscale and 83% (95% CI, 0.7-0.91) and 56% (95% CI, 0.4-0.72) for the UUI-subscale. Youden-index was 0.28 for the SUI-subscale and 0.39 for the UUI-subscale at the given cut-off values. CONCLUSION: Psychometric properties of the German-language QUID are principally good and support its use in the German-speaking area. However, the modest specificity when distinguishing between SUI and UUI should be taken into account. TRIAL REGISTRATION NUMBER: DRKS00018777 (date of registration: 16-January-2020).

Urogynecology in obstetrics: impact of pregnancy and delivery on pelvic floor disorders, a prospective longitudinal observational pilot study.

PURPOSE: To assess changes in the pelvic floor anatomy that cause pelvic floor disorders (PFDs) in primigravidae during and after pregnancy and to evaluate their impact on women's quality of life (QoL). METHODS: POP-Q and translabial ultrasound examination was performed in the third trimester and 3 months after delivery in a cohort of primigravidae with singleton pregnancy delivering in a tertiary center. Results were analyzed regarding mode of delivery and other pre- and peripartal factors. Two individualized detailed questionnaires were distributed at 3 months and at 12 months after childbirth to determinate QoL. RESULTS: We recruited 45 women, of whom 17 delivered vaginally (VD), 11 received a vacuum extraction delivery (VE) and 17 a Cesarean section in labor (CS). When comparing third-trimester sonography to 3 months after delivery, bladder neck mobility increased significantly in each delivery group and hiatal area increased significantly in the VD group. A LAM avulsion was found in two women after VE. Connective tissue weakness (p = 0.0483) and fetal weight at birth (p = 0.0384) were identified as significant risk factors for the occurrence of PFDs in a multivariant regression analysis. Urinary incontinence was most common with 15% and 11% of cases at 3, respectively, 12 months after delivery. 42% of women reported discomfort during sexual intercourse, 3 months after delivery and 24% 12 months postpartum. Although 93% of women engage a midwife after delivery, only 56% participated in pelvic floor muscle training. CONCLUSION: Connective tissue weakness and high fetal weight at birth are important risk factors for the occurrence of PFDs. Nevertheless, more parturients should participate in postpartal care services to prevent future PFDs.

Influences on pathologic complete response in breast cancer patients after neoadjuvant chemotherapy.

PURPOSE: Pathologic complete response is associated with longer disease-free survival and better overall survival after neoadjuvant chemotherapy in breast cancer patients. We, therefore, evaluated factors influencing pathologic complete response. METHODS: Patients receiving neoadjuvant chemotherapy from 2015 to 2018 at the Saarland University Hospital were included. Patients' age, tumor stage, tumor biology, genetic mutation, recurrent cancer, discontinuation of chemotherapy, and participation in clinical trials were extracted from electronic medical records. Binary logistic regression was performed to evaluate the influence of these factors on pathologic complete response. RESULTS: Data of 183 patients were included. The median patient's age was 54 years (22-78). The median interval between diagnosis and onset of chemotherapy was 28 days (14-91); between end of chemotherapy and surgery 28 days (9-57). Sixty-two patients (34%) participated in clinical trials for chemotherapy. A total of 86 patients (47%) achieved pathologic complete response. Patient's age, genetic mutation, recurrent cancers, or discontinuation of chemotherapy (due to side effects) and time intervals (between diagnosis and onset of chemotherapy, as well as between end of chemotherapy and surgery) did not influence pathologic complete response. Patients with high Ki67, high grading, Her2 positive tumors, as well as patients participating in clinical trials for chemotherapy had a higher chance of having pathologic complete response. Patients with Luminal B tumors had a lower chance for pathologic complete response. CONCLUSION: Particularly patients with high risk cancer and patients, participating in clinical trials benefit most from chemotherapy. Therefore, breast cancer patients can be encouraged to participate in clinical trials for chemotherapy.

Students' attitudes toward digital learning during the COVID-19 pandemic: a survey conducted following an online course in gynecology and obstetrics.

PURPOSE: The purpose of this survey was to assess medical students' opinions about online learning programs and their preferences for specific teaching formats during COVID 19 pandemic. METHODS: Between May and July 2020, medical students who took an online gynecology and obstetrics course were asked to fill in a questionnaire anonymously. The questionnaire solicited their opinions about the course, the teaching formats used (online lectures, video tutorials featuring real patient scenarios, and online practical skills training), and digital learning in general. RESULTS: Of 103 students, 98 (95%) submitted questionnaires that were included in the analysis. 84 (86%) students had no problem with the online course and 70 (72%) desired more online teaching in the future. 37 (38%) respondents preferred online to traditional lectures. 72 (74%) students missed learning with real patients. All digital teaching formats received good and excellent ratings from > 80% of the students. CONCLUSION: The survey results show medical students' broad acceptance of the online course during COVID 19 pandemic and indicates that digital learning options can partially replace conventional face-to-face teaching. For content taught by lecture, online teaching might be an alternative or complement to traditional education. However, bedside-teaching remains a key pillar of medical education.

Incidence of and risk factors for vaginal cuff dehiscence following total laparoscopic hysterectomy: a monocentric hospital analysis.

PURPOSE: Vaginal cuff dehiscence (VCD) is one of the major surgical complications following hysterectomy with data on incidence rates varying largely and studies assessing risk factors being sparse with contradictive results. The aim of this study was to assess the incidence rate of and risk factors for VCD in a homogenous cohort of women treated for benign uterine pathologies via total laparoscopic hysterectomy (TLH) with standardized follow-up. METHODS: All patients undergoing TLH at the Department of Gynecology and Obstetrics, Saarland University Hospital between November 2010 and February 2019 were retrospectively identified from a prospectively maintained service database. RESULTS: VCD occurred in 18 (2.9%) of 617 patients included. In univariate and multivariate analyses, a lower level of surgeon laparoscopic expertise (odds ratio 3.19, 95% confidence interval (CI) 1.0-9.38; p = 0.03) and lower weight of removed uterus (odds ratio 0.99, 95% CI 0.98-0.99; p = 0.02) were associated positively with the risk of VCD. CONCLUSION: In this homogenous cohort undergoing TLH, laparoscopic expertise and uterine weight influenced the risk of postoperative VCD. These findings might help to further reduce the rate of this complication.

Cervical and Lower Uterine Parameter Ultrasound and Elastographic Parameters for the Prediction of a Successful Induction of Labor.

PURPOSE: The prediction of successful induction of labor (IOL) has been the subject of a series of studies. The predictive role of cervical sonographic and elastographic parameters has been controversially discussed. Lower uterine segment (LUS) thickness and strain values have not been discussed yet in this regard. MATERIALS AND METHODS: A prospective cohort study was performed to examine the predictive power of Bishop score parameters, sonographic cervical length (CL), cervical funneling, cervical strain values, LUS thickness and its strain values regarding successful IOL within 24 hours and intervals to onset of labor, ROM and delivery of the fetus. A p-value of < 0.05 was considered statistically significant. RESULTS: 135 patients were examined. A cervical length of 25 mm, the presence of cervical funneling and digital shorter cervix was significant for the prediction of successful induction of labor (IOL) within 24 hours. There was weak correlation between the functional CL and the onset of labor (r2 = 0.10) and ROM (r2 = 0.13). There was also a weak correlation between the cervical funnel width and the time interval to the onset of labor (r2 = 0.25), ROM (r2 = 0.23) and delivery of the fetus (r2 = 0.22). Cervical elastography, LUS thickness and strain values were not significant for the prediction of a successful IOL. CONCLUSION: We were able to show that cervical structural changes at the level of the internal os, i. e., shortening through funneling, may be the determining factor for successful IOL.