Lieven Nils Kennes

Objective: The aim of this study was to evaluate the positive predictive value of endocervical curettage (ECC) during colposcopic examination in a dysplasia unit since the implementation of the new cervical cancer screening program in Germany (January 2020). Methods: A total of 202 patients who presented for colposcopy at the Dysplasia Unit of the University Hospital Aachen, Germany, between January 2020 and October 2023, who had cervical intraepithelial neoplasia 1+ (CIN1+) in the endocervical curettage and received a loop-excisional procedure of the cervix (LEEP), were included in a retrospective cohort analysis using machine learning techniques (random forest analysis and leave-one-out cross-validation). Results: There was a low agreement between the results of the ECC and the CIN status after LEEP (kappa 0.0239). A positive result in the histological specimen of the excisional procedure of the cervix (CIN2+) was obtained in 73.7% in case of CIN1 detection in the ECC, 69.4% in case of CIN2 detection in the ECC, and 80.6% in case of CIN3 in the ECC. In the multivariate analysis, the result of colposcopy and the transformation zone, especially combined (kappa 0.259, p = 0.0004), had the highest predictive value with regard to the CIN status. Conclusions: ECC is associated with a low agreement rate in comparison to the final histological result of the LEEP, which should be kept in mind when counseling patients. A finding of CCIN1in an ECC obtained during colposcopy following abnormal HPV-based cervical cancer screening results should be considered an indication of a possible intracervical dysplasia.

Background/Objectives: Endometriosis is a chronic gynecological disorder characterized by ectopic endometrial-like tissue. The symptoms of this disease negatively affect the patient’s quality of life, both physically and mentally. This study aims to identify key factors impacting health-related quality of life in endometriosis patients. Methods: A total of 175 patients from the Endometriosis Centre of the RWTH Aachen University Hospital were assessed using the German version of the EHP-30. The EHP is a patient self-report tool used to measure the wide range of impacts that endometriosis can have on women’s lives (affecting pain levels, leading to feelings of powerlessness and a loss of control, and affecting their emotional well-being, social support, and self-image). Multivariate linear regression and random forest analyses were performed to evaluate predictors of health-related quality of life, focusing on demographic characteristics, pain severity, endometriosis symptoms and planned procedures. Results: Key factors that have a significant negative impact on QoL include higher pain scores, dysuria, and persistent endometriosis. Higher pain scores negatively affect the EHP-30 pain (p < 0.0001), control and powerlessness (p < 0.0001) and emotional well-being (p < 0.01) scores. Dysuria has a negative effect on pain (p < 0.001), control and powerlessness (p < 0.001), emotional well-being (p < 0.05), and social support (p < 0.05). Persistent endometriosis was negatively associated with pain (p < 0.01), control and powerlessness (p < 0.01), and social support. Previous endometriosis surgery has a positive effect on the EHP-30 scores for pain, control and powerlessness, emotional well-being, and self-image (p < 0.05). Conclusions: Our study highlights the multifactorial impact of endometriosis on health-related QoL. Personalized treatments focusing on pain management, emotional support and social interventions are crucial to improve patient outcomes.

Objectives: Transobturator tape (TOT) procedures are a widely used and effective treatment for stress urinary incontinence (SUI), but there is limited research on mesh-related complications and revision surgeries. This study aimed to evaluate the incidence of revision surgeries and mesh-related complications following TOT procedures and identify potential risk factors influencing these outcomes. Methods: This retrospective study analyzed data from patients who underwent TOT procedures at the specialized incontinence center of University Hospital Aachen (UHA), Germany, between January 2010 and May 2023. Patients were divided into three groups: initial surgery without revision, initial surgery with revision, and external referrals requiring revision. Statistical analyses included multivariate logistic regression and predictive cross-validation to identify risk factors for revision and mesh-related complications. Results: Out of 265 TOT procedures performed, the revision rate was 8.7%, and the mesh-related complication rate was 2.6%. Mesh complications, including erosion and wound dehiscence, accounted for 30% of revisions, while 70% of revisions were caused by recurrent stress urinary incontinence (SUI). External referrals showed longer revision intervals compared to UHA patients (53 months vs. 5 months; p = 0.003). Multivariate analysis identified rectoceles as a protective factor against revisions (p = 0.0414), while pre-existing conditions significantly increased revision risk (p = 0.0100). Conclusions: The revision rate following TOT procedures was 8.7%, with mesh-related complications accounting for 2.6%. Pre-existing conditions significantly increased the risk of revision, while rectoceles were associated with improved outcomes. These findings emphasize the importance of identifying patient-specific risk factors to enhance the safety and success of TOT procedures.

It is still unclear how and why some patients develop painful and others painless polyneuropathy. The aim of this study was to identify multiple factors associated with painful polyneuropathies (NeuP). A total of 1181 patients of the multicenter DOLORISK database with painful (probable or definite NeuP) or painless (unlikely NeuP) probable or confirmed neuropathy were investigated clinically, with questionnaires and quantitative sensory testing. Multivariate logistic regression including all variables (demographics, medical history, psychological symptoms, personality items, pain-related worrying, life-style factors, as well as results from clinical examination and quantitative sensory testing) and machine learning was used for the identification of predictors and final risk prediction of painful neuropathy. Multivariate logistic regression demonstrated that severity and idiopathic etiology of neuropathy, presence of chronic pain in family, Patient-Reported Outcomes Measurement Information System Fatigue and Depression T-Score, as well as Pain Catastrophizing Scale total score are the most important features associated with the presence of pain in neuropathy. Machine learning (random forest) identified the same variables. Multivariate logistic regression archived an accuracy above 78%, random forest of 76%; thus, almost 4 out of 5 subjects can be classified correctly. This multicenter analysis shows that pain-related worrying, emotional well-being, and clinical phenotype are factors associated with painful (vs painless) neuropathy. Results may help in the future to identify patients at risk of developing painful neuropathy and identify consequences of pain in longitudinal studies.

The aim was to compare transperineal ultrasound (TPU) with parameters of the Bishop Score during the first stage of labour and evaluate how TPU can contribute towards improving labour management. Digital examination (DE) and TPU were performed on 42 women presenting at the labour ward with regular contractions. TPU measurements included the head–symphysis distance, angle of progression, diameter of the cervical wall, cervical dilation (CD) and cervical length (CL). To examine if TPU can monitor labour progress, correlations of TPU parameters were calculated. Agreement of DE and TPU was examined for CL and CD measurements and for two groups divided into latent (CD < 5 cm) and active stages of labour (CD ≥ 5 cm). TPU parameters indicated a moderate negative correlation of CD and CL (Pearson: r = −0.667; Spearman = −0.611). The other parameters showed a weak to moderate correlation. DE and TPU measurements for CD showed better agreement during the latent stage than during the active stage. The results of the present study add to the growing evidence that TPU may contribute towards an improved labour management, suggesting a combined approach of TPU and DE to monitor the latent first stage of labour and using only DE during the active stage of labour.

Urinary incontinence (UI) could negatively affect a person’s quality of life (QoL). This study investigates the association among gynecological cancers, their treatments, UI, and its effect on the QoL of survivors of gynecological cancer. This cross-sectional questionnaire-based study included 121 cases from 405 patients who had undergone gyneco-oncological therapy. The participants were asked whether they experienced any form of UI and whether it impacted their QoL. The following therapies were used to treat the 12 gynecologic tumor types found in the participants: surgery (n = 116, 95.87%), chemotherapy (CTx) (n = 51, 42.2%), radiotherapy (RTx) (n = 31, 25.6%), and antibody therapy (ABT) (n = 11, 9.1%). No significant association was determined between tumor type and UI. However, body mass index (BMI), radical hysterectomy, vulvar or vaginal surgery, and presence of UI before treatment had significant impacts on the presence of UI. The surgical access routes, CTx, ABT, and hysterectomy had significant impacts on the severity of UI after treatment. Among all patients, 55.4% reported very good QoL. These reports of good QoL by patients could be due to their very good adjustment to the situation, with regard to being diagnosed with and receiving treatment for cancer, or due to the patients considering UI to not be much of an issue. Additionally, 34% of patients reported they had not been informed about the risk of UI before treatment. Informing patients about UI as one of the risks of therapy before initiating the treatment is crucial as patients who had been informed beforehand coped with UI far better than those who were not informed. Hence, the treatment of UI is often successful, so patients should be encouraged to receive urogynecological consultation.

Summary: MCP‐Mod has been proposed as analysis method for investigating the dose‐response (DR) relationship and dose finding in clinical Phase II trials. The original methodology as well as several generalizations are well accepted by Health Authorities. In this paper, we investigate the application of the generalized MCP‐Mod approach in chronic pain, a challenging therapeutic area with primary endpoints based on patient reported outcomes, repeatedly measured over time, with high inter‐subject variability and potentially high premature discontinuation rates. In a simulation study, we investigate the impact of several study design factors on the ability to establish proof of concept, to derive information on the functional DR relationship, and to estimate target doses of interest (eg, ED80). Furthermore, different methods to derive confidence intervals for the target doses of interest are compared regarding their coverage rates and widths. Proof of concept is well established by MCP‐Mod even in longitudinal trials with high inter‐subject variability. While the most reasonable DR model is also selected in most cases, estimated target doses and their bootstrap confidence intervals have to be treated with some caution, if trial data are strongly affected by individual heterogeneity as observed in two recent chronic pain trials. We describe encountered challenges and provide recommendations for designing future dose ranging longitudinal trials with high inter‐subject variability under model uncertainty.

Randomized controlled clinical trials are regarded as the gold standard for comparing different clinical interventions, but generally their conduct is operationally cumbersome, time-consuming, and expensive. Studies and investigations based on clinical routine data on the contrary utilize existing data acquired under real-life conditions and are increasingly popular among practitioners. In this paper, methodological aspects of studies based on clinical routine data are discussed. Important limitations and considerations as well as unique strengths of these types of studies are indicated and exemplarily demonstrated in a recent real-case study based on clinical routine data. In addition two simulation studies reveal the impact of bias in studies based on clinical routine data on the type I error rate and false decision rate in favor of the inferior intervention. It is concluded that correctly analyzing clinical routine data yields a valuable addition to clinical research; however, as a result of a lack of statistical foundation, internal validity, and comparability, generalizing results and inferring properties derived from clinical routine data to all patients of interest has to be considered with extreme caution.