Tomas Kupec

Background: Endometriosis is a chronic inflammatory and estrogen-dependent disease in which oxidative stress, immune dysregulation, and lesion-supportive microenvironmental signaling contribute to lesion development. N-acetylcysteine (NAC), a glutathione-replenishing and redox-modulating agent, has been studied as a possible non-hormonal intervention. Methods: Following preregistration in the Open Science Framework (OSF), we performed a PRISMA-compliant systematic review of studies evaluating NAC in endometriosis-related clinical, in vivo, ex vivo, or in vitro settings. We searched PubMed/MEDLINE, EBSCOhost, and the Bielefeld Academic Search Engine (BASE) from inception to 24 May 2026. Risk of bias was assessed with design-specific instruments. Results: Twenty-two studies were included. Clinical evidence comprised six studies and suggested that the findings vary by clinical context. In non-postoperative settings, NAC was associated with reduced pain, decreased NSAID use, and endometrioma shrinkage or stabilization. In contrast, the only postoperative randomized comparison found no added benefit of NAC over continuous oral contraceptive therapy for recurrence or pain. Fertility-related clinical findings were suggestive but preliminary. Across nonclinical models, NAC reduced proliferation, lesion burden, oxidative stress, inflammatory mediators, and, in selected systems, migration-related behavior. Mechanistic studies linked NAC to modulation of ROS-dependent proliferation, TNF-α, COX-2, MMP-2/-9, autophagy-related signaling, oxidation-sensitive nociception, and partial protection of oocyte and embryo competence under endometriosis-associated oxidative conditions. Conclusions: NAC shows biological plausibility and preclinical activity in endometriosis, but clinical evidence is heterogeneous and methodologically limited.

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: Endometriosis is a chronic gynecological disease associated with pain, infertility, and delayed diagnosis. Non-invasive biomarkers are urgently needed to facilitate earlier detection and reduce the reliance on diagnostic laparoscopy. MicroRNAs (miRNAs) are stable in body fluids and hold promise as diagnostic tools. Methods: In this pilot study, urine samples from 34 patients with histologically confirmed endometriosis and 18 control patients (laparoscopically confirmed absence of disease) were analyzed using next-generation miRNA sequencing. Differential expression analysis was performed with DESeq2. Feature selection applied variance filtering, univariate analysis, mutual information, and recursive feature elimination (RFE). The top 20 miRNAs were used to train four classification models: logistic regression, decision tree, random forest, and support vector machine (SVM). Model performance was evaluated by accuracy, precision, recall, F1-score, and area under the ROC curve (AUC). Results: Among all detected miRNAs, hsa-miR-10400-5p was significantly downregulated in endometriosis compared to controls (log₂ fold change − 2.70; adjusted p = 0.015). RFE identified 20 miRNAs, including hsa-mir-183, hsa-mir-500a, hsa-miR-3184-5p, hsa-miR-151b, and hsa-mir-196a-1, as the most informative for classification. The random forest model achieved the best performance (AUC = 0.91; accuracy and F1-score = 0.81), outperforming logistic regression (AUC = 0.83) and SVM (AUC = 0.81). Several identified miRNAs have been previously implicated in endometriosis pathogenesis, and we additionally identified hsa-miR-10400-5p as a significantly downregulated and previously unreported biomarker candidate, representing a novel finding with potential diagnostic relevance. Conclusions: Urinary miRNA profiling, combined with machine learning, shows promise as a completely non-invasive approach for the diagnosis of endometriosis. The identified miRNA signature, particularly the novel hsa-miR-10400-5p, warrants validation in larger, independent cohorts to confirm its clinical utility and potential to reduce diagnostic delays.

Background: Adenomyosis remains difficult to diagnose non-invasively due to clinical overlap with endometriosis and the limited specificity of imaging techniques. This pilot study evaluated whether serum- and urine-derived microRNA (miRNA) profiles, combined with machine-learning approaches, could support non-invasive diagnosis. Methods: Serum and urine samples were collected from 59 patients undergoing surgery for chronic pelvic pain at the Endometriosis Centre of RWTH Aachen University Hospital. Seven patients had isolated adenomyosis, 34 had histologically confirmed endometriosis, and 18 served as negative controls. miRNAs were profiled using next-generation sequencing. A structured feature-selection pipeline (variance filtering, univariate testing, mutual information, recursive feature elimination) was applied before training Logistic Regression, Random Forest, Support Vector Machine, and Decision Tree models using cross-validation. Model performance was evaluated using accuracy, precision, recall, F1 score, and ROC-AUC. Results: Distinct miRNA signatures were detected in both serum and urine, with urine-based models showing superior discriminatory performance. Logistic Regression and Support Vector Machine achieved excellent separation in urine datasets, although perfect AUC values must be interpreted cautiously due to the small number of adenomyosis cases. In serum, Random Forest achieved the highest AUC values (up to 0.98). Several miRNAs, including miR-183-3p, miR-320d-2, and miR-17, emerged as promising candidate biomarkers for differentiating adenomyosis from endometriosis and from negative controls. Conclusions: This pilot study demonstrates the feasibility of liquid-biopsy miRNA profiling combined with machine learning for non-invasive adenomyosis detection. Although results are preliminary and require validation in larger cohorts, urine miRNA profiles may represent a promising complementary tool to improve diagnostic accuracy and reduce diagnostic delay.

Background: Endometriosis is a chronic gynecological condition marked by ectopic endometrial-like tissue, leading to inflammation, pain, and infertility. Diagnosis is often delayed by up to 10 years. Identifying non-invasive biomarkers could facilitate earlier detection. MicroRNAs, known for their stability in biological fluids and role in disease processes, have emerged as potential diagnostic tools. This pilot study investigated whether serum miRNA profiling can differentiate endometriosis from other causes of chronic pelvic pain. Methods: Serum samples from 52 patients (36 with laparoscopically confirmed endometriosis and 16 controls) treated for chronic pelvic pain at a University Endometriosis Centre were analyzed. High-throughput miRNA sequencing was performed. Feature selection reduced 4285 miRNAs to the 20 most informative MiRNAs. Machine learning models, including logistic regression, decision tree, random forest, and support vector machine, were trained and evaluated. Results: Among the tested machine learning models, support vector machine achieved the best overall performance (accuracy 0.71, precision 0.80), while logistic regression and random forest showed the highest AUC values (0.84 and 0.81, respectively), indicating strong diagnostic potential of serum miRNA profiling. Conclusions: This study demonstrates the feasibility of using serum miRNA profiling combined with machine learning for the non-invasive classification of endometriosis. The identified miRNA signature shows strong diagnostic potential and could contribute to earlier and more accurate detection of the disease.

Background and Clinical Significance: A vesicocervical fistula is an abnormal connection between the urinary tract and the cervix. With the increased prevalence of cesarean sections in recent years, the incidence of vesicocervical fistulas has also increased. The objective of this study was to evaluate the available evidence regarding the laparoscopic approach and to present a case study of a patient who underwent minimally invasive repair of a vesicocervical fistula after vacuum delivery. Case Presentation: A 32-year-old mother was admitted to our center with symptoms of urine leakage through the cervix uteri 5 days after vacuum-assisted delivery. In particular, the patient had recently undergone a vacuum-assisted delivery and cesarean section. A positive methylene blue staining test and transvaginal ultrasonography demonstrated an anatomical connection between the bladder and the cervix. Surgical repair of the vesicocervical fistula was performed under general anesthesia and a Foley catheter was inserted for 7 days. Urodynamic studies conducted seven days postoperative and six weeks post-surgery showed normal bladder function and capacity. Conclusions: Early detection and surgical correction of vesicocervical fistulas using a minimally invasive approach is crucial for the treatment of this condition. This case report emphasizes the importance of considering vesicocervical fistulas, particularly in patients with a history of cesarean section who have undergone vacuum-assisted delivery.

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.

Purpose: To evaluate the main factors influencing anxiety in endometriosis patients presenting to an endometriosis centre in Germany. Methods: One hundred and eighty-two patients were asked to complete the German version of the STAI (state anxiety and trait anxiety) questionnaire prior to examination for diagnosis and treatment of pelvic pain or suspected endometriosis. Typical endometriosis symptoms, main complaints, operations, type of endometriosis and planned treatment were analyzed as influencing factors of anxiety in endometriosis patients. We performed linear multiple regression analyses using the forward stepwise method to test which characteristics associated with endometriosis symptoms were associated with trait anxiety and state anxiety. Results: Analysis of the STAI results showed that higher levels of trait anxiety were found in patients with ovarian endometriosis: t (177) = 3.06, p = 0.003 and in patients with symptoms of dyspareunia: t (177) = 2.36, p < 0.020). On the other hand, patients with recurrent endometriosis showed lower levels of trait anxiety: t (177) = − 2.39, p = 0.018. Significantly higher levels of state anxiety were found in patients with persistent endometriosis: t (177) = − 2.45, p = 0.015 and in women with endometriosis who were indicated for surgical therapy: t (177) = 3.89, p < 0.001. Conclusions: We were able to show that higher levels of ongoing anxiety in endometriosis patients are associated with dyspareunia and ovarian endometriosis, which may have a negative impact on partnership and desire to have children. On the other hand, patients with persistent endometriosis or a type of disease that requires surgery have higher levels of immediate situational anxiety.

Endometriosis is a chronic disease associated with pain that affects at least 10% of all women of reproductive age. The symptoms of endometriosis have a negative impact on quality of life; they limit the patient physically and psychologically and are the cause of significant anxiety. The aim of our study was to investigate the anxiety levels of women presenting to our specialized endometriosis outpatient clinic at the RWTH Aachen University Hospital. We sought to record their anxiety symptoms and investigate the effect of extensive counseling on anxiety in patients with endometriosis. We hypothesized that detailed counseling and the planning of multimodal endometriosis therapy would reduce anxiety.Data from 183 patients with lower abdominal pain or suspected endometriosis were analyzed. Prior to the examination, the patients completed a standardized anamnesis form including the German version of the STAI (State Trait Anxiety Inventory). The diagnosis of endometriosis was made in accordance with the recent ESHRE guideline and was based on anamnesis, gynecological examination, and ultrasound by a specialist senior physician with many years of experience in treating endometriosis.Prior to the medical examination, we observed a mean STAI-State score of 48.44 ± 11.56 and STAI-Trait score 45.68 ± 11.27. Following medical examination and planning of multimodal therapy, there was a significant decrease in the mean STAI-State score from 48.44 ± 11.56 to 42.43 ± 10.01 (p < 0.0001) and a minimal but significant decrease in the mean STAI-Trait score from 45.68 ± 11.27 to 45.01 ± 11.57 (p < 0.05).Our study showed that endometriosis is associated with high levels of anxiety. Detailed counseling and the planning of a multimodal therapy led to a significant improvement in anxiety levels.

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.