First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors.

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors. TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of 16 patients. IMA202 consists of autologous genetically modified cytotoxic CD8+ T cells expressing a T cell receptor (TCR), which is specific for a nine amino acid peptide derived from MAGEA1. Eligible patients underwent leukapheresis, T cells were isolated, transduced with lentiviral vector carrying MAGEA1-specific TCR and following lymphodepletion (fludarabine/cyclophosphamide), infused with a median of 1.4×109 specific T cells (range, 0.086×109-2.57×109) followed by interleukin 2. SAFETY OF IMA202: No DLT was observed. The most common grade 3-4 adverse events were cytopenias, that is, neutropenia (81.3%), lymphopenia (75.0%), anemia (50.0%), thrombocytopenia (50.0%) and leukopenia (25.0%). 13 patients experienced cytokine release syndrome, including one grade 3 event. Immune effector cell-associated neurotoxicity syndrome was observed in two patients and was grade 1 in both. EFFICACY OF IMA202: Of the 16 patients dosed, 11 (68.8%) patients had stable disease (SD) as their best overall response (Response Evaluation Criteria in Solid Tumors V.1.1). Five patients had initial tumor shrinkage in target lesions and one patient with SD experienced continued shrinkage in target lesions for 3 months in total but had to be classified as progressive disease due to progressive non-target lesions. IMA202 T cells were persistent in peripheral blood for several weeks to months and were also detectable in tumor tissue. Peak persistence was higher in patients who received higher doses. CONCLUSION: In conclusion, IMA202 had a manageable safety profile, and it was associated with biological and potential clinical activity of MAGEA1-targeting genetically engineered TCR-T cells in a poor prognosis, multi-indication solid tumor cohort. TRIAL REGISTRATION NUMBERS: NCT04639245, NCT05430555.

Unconscious activation of negative emotional memories increases pain unpleasantness.

OBJECTIVE: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall). METHODS: 72 healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral & 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial. RESULTS: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative vs. neutral images (5.52 [SD = 2.06] vs. 5.23 [SD = 2.10]; p = 0.02). This pattern was also present when comparing cues to remembered negative vs. neutral images (5.62 [SD = 1.94] vs. 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative vs. neutral images when remembered (5.48 [SD = 1.79] vs. 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] vs. 5.16 [SD = 1.93]; p = 0.30). CONCLUSIONS: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to non-recallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.

Automated Electrodermal Activity and Facial Expression Analysis for Continuous Pain Intensity Monitoring on the X-ITE Pain Database.

This study focuses on improving healthcare quality by introducing an automated system that continuously monitors patient pain intensity. The system analyzes the Electrodermal Activity (EDA) sensor modality modality, compares the results obtained from both EDA and facial expressions modalities, and late fuses EDA and facial expressions modalities. This work extends our previous studies of pain intensity monitoring via an expanded analysis of the two informative methods. The EDA sensor modality and facial expression analysis play a prominent role in pain recognition; the extracted features reflect the patient's responses to different pain levels. Three different approaches were applied: Random Forest (RF) baseline methods, Long-Short Term Memory Network (LSTM), and LSTM with the sample-weighting method (LSTM-SW). Evaluation metrics included Micro average F1-score for classification and Mean Squared Error (MSE) and intraclass correlation coefficient (ICC [3, 1]) for both classification and regression. The results highlight the effectiveness of late fusion for EDA and facial expressions, particularly in almost balanced datasets (Micro average F1-score around 61%, ICC about 0.35). EDA regression models, particularly LSTM and LSTM-SW, showed superiority in imbalanced datasets and outperformed guessing (where the majority of votes indicate no pain) and baseline methods (RF indicates Random Forest classifier (RFc) and Random Forest regression (RFr)). In conclusion, by integrating both modalities or utilizing EDA, they can provide medical centers with reliable and valuable insights into patients' pain experiences and responses.

Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer.

IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with T-cell products. IMA101 treatment was feasible and well tolerated. The most common adverse events were cytokine release syndrome (Grade 1, n = 6; Grade 2, n = 4) and expected cytopenias. No patient died during the first 100 days after T-cell therapy. No neurotoxicity was observed. No objective responses were noted. Prolonged disease stabilization was noted in three patients lasting for 13.7, 12.9, and 7.3 months. High frequencies of target-specific T cells (up to 78.7% of CD8+ cells) were detected in the blood of treated patients, persisted for >1 year, and were detectable in posttreatment tumor tissue. Individual T-cell receptors (TCR) contained in T-cell products exhibited broad variation in TCR avidity, with the majority being low avidity. High-avidity TCRs were identified in some patients' products. This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs. See related Spotlight by Uslu and June, p. 865.

The impact of analgesic on EMG and other biosignals in a postoperative setting.

Background: In the clinical context, the assessment of pain in patients with inadequate communication skills is standardly performed externally by trained medical staff. Automated pain recognition (APR) could make a significant contribution here. Hereby, pain responses are captured using mainly video cams and biosignal sensors. Primary, the automated monitoring of pain during the onset of analgesic sedation has the highest relevance in intensive care medicine. In this context, facial electromyography (EMG) represents an alternative to recording facial expressions via video in terms of data security. In the present study, specific physiological signals were analyzed to determine, whether a distinction can be made between pre-and post-analgesic administration in a postoperative setting. Explicitly, the significance of the facial EMG regarding the operationalization of the effect of analgesia was tested. Methods: N = 38 patients scheduled for surgical intervention where prospectively recruited. After the procedure the patients were transferred to intermediate care. Biosignals were recorded and all doses of analgesic sedations were carefully documented until they were transferred back to the general ward. Results: Almost every biosignal feature is able to distinguish significantly between 'before' and 'after' pain medication. We found the highest effect sizes (r = 0.56) for the facial EMG. Conclusion: The results of the present study, findings from research based on the BioVid and X-ITE pain datasets, staff and patient acceptance indicate that it would now be appropriate to develop an APR prototype.

Immersive medium for early clinical exposure - knowledge acquisition, spatial orientation and the unexpected role of annotation in 360° VR photos.

Aim: 360° VR photos could be a low-threshold possibility to increase early clinical exposure. Apart from granting insights into local routines and premises, the medium should facilitate knowledge acquisition and spatial orientation depending on its design. This assumption, however, is not yet substantiated empirically. Thus, three hypotheses were tested in consideration of Mayer's modality principle: 1) Providing 360° VR photos as visual reference improves retention and comprehension of information. 2) The annotation of text boxes in 360° VR photos compromises spatial orientation and presence. 3) Annotated audio commentary is superior to annotated text boxes in terms of cognitive load and knowledge acquisition. Methods: Using head-mounted displays, students of human (N=53) and dental medicine (N=8) completed one of three virtual tours through a surgical unit, which were created with 360° VR photos. In the first two variants, information about the facilities, medical devices and clinical procedures was annotated either as text boxes or audio commentary comprising 67 words on average (SD=6.67). In the third variant, the same information was given separately on a printed handout before the virtual tour. Taking user experience and individual learner characteristics into account, differences between conditions were measured regarding retention, comprehension, spatial orientation, cognitive load, and presence. Results: Concerning retention and comprehension of information, annotated text boxes outperformed annotated audio commentary and the handout condition. Although annotated audio commentary exhibited the lowest knowledge test scores, students preferred listening over reading. Students with an interest in VR and 360° media reported higher levels of enjoyment and presence. Regarding spatial orientation and presence, no significant group differences were found. Conclusions: 360° VR photos can convey information and a sense of spatial orientation effectively in the same learning scenario. For students, their use is both enjoyable and instructive. Unexpectedly, the ideal mode of annotation is not dictated by Mayer's modality principle. For information like in this study, annotated text boxes are better for knowledge acquisition than the subjectively preferred audio commentary. This finding is probably contingent on the length and the quality of the annotated text. To identify boundary conditions and to validate the findings, more research is required on the design and educational use of 360° VR photos.

Single channel approach for filtering electroencephalographic signals strongly contaminated with facial electromyography.

Eliminating facial electromyographic (EMG) signal from the electroencephalogram (EEG) is crucial for the accuracy of applications such as brain computer interfaces (BCIs) and brain functionality measurement. Facial electromyography typically corrupts the electroencephalogram. Although it is possible to find in the literature a number of multi-channel approaches for filtering corrupted EEG, studies employing single-channel approaches are scarce. In this context, this study proposed a single-channel method for attenuating facial EMG noise from contaminated EEG. The architecture of the method allows for the evaluation and incorporation of multiple decomposition and adaptive filtering techniques. The decomposition method was responsible for generating EEG or EMG reference signals for the adaptive filtering stage. In this study, the decomposition techniques CiSSA, EMD, EEMD, EMD-PCA, SSA, and Wavelet were evaluated. The adaptive filtering methods RLS, Wiener, LMS, and NLMS were investigated. A time and frequency domain set of features were estimated from experimental signals to evaluate the performance of the single channel method. This set of characteristics permitted the characterization of the contamination of distinct facial muscles, namely Masseter, Frontalis, Zygomatic, Orbicularis Oris, and Orbicularis Oculi. Data were collected from ten healthy subjects executing an experimental protocol that introduced the necessary variability to evaluate the filtering performance. The largest level of contamination was produced by the Masseter muscle, as determined by statistical analysis of the set of features and visualization of topological maps. Regarding the decomposition method, the SSA method allowed for the generation of more suitable reference signals, whereas the RLS and NLMS methods were more suitable when the reference signal was derived from the EEG. In addition, the LMS and RLS methods were more appropriate when the reference signal was the EMG. This study has a number of practical implications, including the use of filtering techniques to reduce EEG contamination caused by the activation of facial muscles required by distinct types of studies. All the developed code, including examples, is available to facilitate a more accurate reproduction and improvement of the results of this study.

Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy.

T cell receptor (TCR)-based immunotherapy has emerged as a promising therapeutic approach for the treatment of patients with solid cancers. Identifying peptide-human leukocyte antigen (pHLA) complexes highly presented on tumors and rarely expressed on healthy tissue in combination with high-affinity TCRs that when introduced into T cells can redirect T cells to eliminate tumor but not healthy tissue is a key requirement for safe and efficacious TCR-based therapies. To discover promising shared tumor antigens that could be targeted via TCR-based adoptive T cell therapy, we employed population-scale immunopeptidomics using quantitative mass spectrometry across ~1500 tumor and normal tissue samples. We identified an HLA-A*02:01-restricted pan-cancer epitope within the collagen type VI α-3 (COL6A3) gene that is highly presented on tumor stroma across multiple solid cancers due to a tumor-specific alternative splicing event that rarely occurs outside the tumor microenvironment. T cells expressing natural COL6A3-specific TCRs demonstrated only modest activity against cells presenting high copy numbers of COL6A3 pHLAs. One of these TCRs was affinity-enhanced, enabling transduced T cells to specifically eliminate tumors in vivo that expressed similar copy numbers of pHLAs as primary tumor specimens. The enhanced TCR variants exhibited a favorable safety profile with no detectable off-target reactivity, paving the way to initiate clinical trials using COL6A3-specific TCRs to target an array of solid tumors.

FSFI score and timing of tubal ligation in patients: preliminary results of an online survey.

INTRODUCTION: Tubal ligation is the most common contraceptive method worldwide. Apart from a very low pearl index and anxiety relief, other benefits are not commonly recognised. In young patients, there is the post-operative risk of regretting the decision with the need for In-Vitro-Fertilisation or refertilising surgery. Positive side effects have not been widely published. In our study we investigated the change in the female sexual function index score after tubal ligation. MATERIAL AND METHOD: In this survey the FSFI score of participants around the time of the tubal ligation was compared with the FSFI score of intermediate and long-term time distance to the ligation. RESULTS: The data indicate an increase in younger women seeking information on permanent contraception and whilst the FSFI score of the early group indicates a risk of female sexual dysfunction, the intermediate and long-term FSFI scores are comparable to published control groups. DISCUSSION: Besides the obvious benefit of a low pearl index, tubal ligation may contribute to reduce the risk of female sexual dysfunction in the mid and long term. Informed consent is essential for the surgeon and patient to weigh up the risks and benefits individually including possible future perspectives on family planning.

Measurement of the nociceptive flexion reflex threshold in critically ill patients - a randomized observational pilot study.

BACKGROUND: Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. METHODS: This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). RESULTS: 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 - NFRT: 59.40 vs. RASS -4 - NFRT: 29.00, p < 0.001). CONCLUSIONS: NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ -4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. TRIAL REGISTRATION: Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149 .

Skepticism towards advancing VR technology - student acceptance of VR as a teaching and assessment tool in medicine.

Objective: The high didactic potential of Virtual Reality (VR) contrasts with the point of view of students that the technology only has a relatively low significance for current and future teaching. This discrepancy was studied in a differentiated manner in order to gear the further development and implementation of VR towards the target group. Methods: From January 2020 to July 2020, medical students (N=318) were asked to watch ten videos online and rate them on the basis of acceptance indicators (e.g., fun and fairness). Using obstetrics as an example, the videos demonstrated five levels of VR technology functionality (e.g., haptic and adaptive feedback), some of which were visionary, in two use scenarios (teaching and the OSCE). The individual and aggregate indicators were compared with non-parametric testing procedures across application scenarios, functional levels and genders. In addition, correlations between the acceptance and the factors of semester, age, computer affinity, and previous VR experience were analyzed. Results: Across all functional levels, VR was more likely to be accepted in the classroom than in the OSCE. Comparisons across functional levels also revealed that the VR ready to be marketed was significantly more accepted than the visionary functions. This skepticism toward advancing VR technology was most pronounced with regard to the vision of autonomous VR examinations and among female students with a low computer affinity. Conclusion: The results suggest that the students' reservations are due to a lack of experience with the VR technology. In order for young physicians to become familiar with the technology and to be able to use it competently in the everyday clinical practice in the future, VR should not only be used as a teaching tool but also be part of the curriculum. Practical examinations using VR, on the other hand, are only recommended once the technology has become established in teaching and has been proven to be reliable.

Autonomous Nervous Response During Sedation in Colonoscopy and the Relationship With Clinician Satisfaction.

Background: Nurse assisted propofol sedation (NAPS) is a common method used for colonoscopies. It is safe and widely accepted by patients. Little is known, however, about the satisfaction of clinicians performing colonoscopies with NAPS and the factors that negatively influence this perception such as observer-reported pain events. In this study, we aimed to correlate observer-reported pain events with the clinicians' satisfaction with the procedure. Additionally, we aimed to identify patient biosignals from the autonomic nervous system (B-ANS) during an endoscopy that correlate with those pain events. Methods: Consecutive patients scheduled for a colonoscopy with NAPS were prospectively recruited. During the procedure, observer-reported pain events, which included movements and paralinguistic sounds, were simultaneously recorded with different B-ANS (facial electromyogram (EMG), skin conductance level, body temperature and electrocardiogram). After the procedure, the examiners filled out the Clinician Satisfaction with Sedation Instrument (CSSI). The primary endpoint was the correlation between CSSI and observer-reported pain events. The second primary endpoint was the identification of B-ANS that make it possible to predict those events. Secondary endpoints included the correlation between CSSI and sedation depth, the frequency and dose of sedative use, polyps resected, resection time, the duration of the procedure, the time it took to reach the coecum and the experience of the nurse performing the NAPS. ClinicalTrials.gov: NCT03860779. Results: 112 patients with 98 (88.5%) available B-ANS recordings were prospectively recruited. There was a significant correlation between an increased number of observer-reported pain events during an endoscopy with NAPS and a lower CSSI (r = -0.318, p = 0.001). Additionally, the EMG-signal from facial muscles correlated best with the event time points, and the signal significantly exceeded the baseline 30 s prior to the occurrence of paralinguistic sounds. The secondary endpoints showed that the propofol dose relative to the procedure time, the cecal intubation time, the time spent on polyp removal and the individual nurse performing the NAPS significantly correlated with CSSI. Conclusion: This study shows that movements and paralinguistic sounds during an endoscopy negatively correlate with the satisfaction of the examiner measured with the CSSI. Additionally, an EMG of the facial muscles makes it possible to identify such events and potentially predict their occurrence.

Automatic vs. Human Recognition of Pain Intensity from Facial Expression on the X-ITE Pain Database.

Prior work on automated methods demonstrated that it is possible to recognize pain intensity from frontal faces in videos, while there is an assumption that humans are very adept at this task compared to machines. In this paper, we investigate whether such an assumption is correct by comparing the results achieved by two human observers with the results achieved by a Random Forest classifier (RFc) baseline model (called RFc-BL) and by three proposed automated models. The first proposed model is a Random Forest classifying descriptors of Action Unit (AU) time series; the second is a modified MobileNetV2 CNN classifying face images that combine three points in time; and the third is a custom deep network combining two CNN branches using the same input as for MobileNetV2 plus knowledge of the RFc. We conduct experiments with X-ITE phasic pain database, which comprises videotaped responses to heat and electrical pain stimuli, each of three intensities. Distinguishing these six stimulation types plus no stimulation was the main 7-class classification task for the human observers and automated approaches. Further, we conducted reduced 5-class and 3-class classification experiments, applied Multi-task learning, and a newly suggested sample weighting method. Experimental results show that the pain assessments of the human observers are significantly better than guessing and perform better than the automatic baseline approach (RFc-BL) by about 1%; however, the human performance is quite poor due to the challenge that pain that is ethically allowed to be induced in experimental studies often does not show up in facial reaction. We discovered that downweighting those samples during training improves the performance for all samples. The proposed RFc and two-CNNs models (using the proposed sample weighting) significantly outperformed the human observer by about 6% and 7%, respectively.

[Reconciliation of Family and Work Life in the Department of Gynecology and Obstetrics - Systematic Assessment in Different Occupational Groups of a German University Hospital]. / "Zur Vereinbarkeit von Beruf und Familie bei Beschäftigten einer Universitätsfrauenklinik" ­ Auswertung einer systematischen Berufsgruppen-übergreifenden Befragung.

Reconciliation of family and work life is an important topic for employees. Due to common work in shifts within the health care sector, this is even more essential for health care workers and has great implications in work satisfaction and individuals ́ health. Within all employees of the department of OB/GYN of the German university hospital Ulm, an anonymous and voluntary survey on compatibility of work and family was performed in the summer of 2017. The questionnaires consisted of established and newly designed tools to assess reconciliation of family/work life as well as work-family (WFC) and family-work conflict (FWC). Return rate of questionnaires was 63% (n=136). Physicians (n=33), nurses (n=53), and midwives (n=31) were grouped together as "medical staff" (n=115). There was no significant difference between employees with (n=73) or without children (n=59) regarding WFC and FWC. The group of nurses/midwives and the group of physicians had a significantly higher inter-role conflict (p<0.001) than the group of administrative staff. A negative correlation with "work satisfaction" was found for WFC and FWC. The group of nurses/midwives has significantly higher inter-role conflicts than the administrative staff. Especially the negative correlation of work satisfaction and inter-role conflicts shows the enormous need for improvement in sufficient compatibility of work and family life of employees in the health care sector. This needs to be addressed quickly and effectively as there is an alarming deficit of nurses and midwives in the German health care system.

Choosing a Surgical Access Point for Hysterectomy: A Paradigm Shift Over a 10-Year Span.

Background: When choosing a surgical procedure for a hysterectomy, doctors and patients have various options in terms of the multiple surgical access points available. The aim of this study was to descriptively analyze developments concerning the surgical access point selected over the past 10 years at Ulm University Hospital, (south) Germany, assess the variables associated with the surgical method and explore any potential significant correlations that influence these surgical access routes. Explicitly, we wished to investigate whether the approval of ulipristal acetate and the warning issued by the Food and Drug Administration (FDA) in connection with its use changed existing trends. Material and Methods: This monocentric study retrospectively assessed data from all patients who underwent a hysterectomy due to a benign disease or endometrial cancer from January 2007 until December 2016. Results: Of the benign indications considered, myomas and descensus genitalis occurred most frequently (49.5 and 30.6%, respectively). The percentage of abdominal procedures declined from 61.4 to 13.4% between 2007 and 2016 for all hysterectomies, whilst it increased from 4.1 to 69.7% for laparoscopic hysterectomies. The rate of vaginal hysterectomies increased to 45.5% until 2013 and declined in the years afterwards. Laparoscopic assisted vaginal hysterectomies were comparatively rare. The trends in terms of surgical routes were similar for endometrial cancer. During the observation period, the share of abdominal hysterectomies fell from 100 to 11.3%, whilst the share of laparoscopic hysterectomies increased from 0 to 86.6%. The other two procedures were less frequently used. Use of the laparoscopic hysterectomy procedure also increased significantly after the FDA's 2014 warning. Ulipristal acetate may have tended to influence the process. Conclusion: Contrary to the national decrease in hysterectomy numbers, the annual number of hysterectomies at Ulm University Hospital remained stable during the observation period. Nevertheless, there was a clear shift in the preferred surgical routes for hysterectomy.

Evaluation of an Objective Measurement Tool for Stress Level Reduction by Individually Chosen Music During Colonoscopy-Results From the Study "ColoRelaxTone".

Background and Aims: Colonoscopy as standard procedure in endoscopy is often perceived as uncomfortable for patients. Patient's anxiety is therefore a significant issue, which often lead to avoidance of participation of relevant examinations as CRC-screening. Non-pharmacological anxiety management interventions such as music might contribute to relaxation in the phase prior and during endoscopy. Although music's anxiolytic effects have been reported previously, no objective measurement of stress level reduction has been reported yet. Focus of this study was to evaluate the objective measurement of the state of relaxation in patients undergoing colonoscopy. Methods: Prospective study (n = 196) performed at one endoscopic high-volume center. Standard colonoscopy was performed in control group. Interventional group received additionally self-chosen music over earphones. Facial Electromyography (fEMG) activity was obtained. Clinician Satisfaction with Sedation Instrument (CSSI) and Patients Satisfaction with Sedation Instrument (PSSI) was answered by colonoscopists and patients, respectively. Overall satisfaction with music accompanied colonoscopy was obtained if applicable. Results: Mean difference measured by fEMG via musculus zygomaticus major indicated a significantly lower stress level in the music group [7.700(±5.560) µV vs. 4.820(±3.330) µV; p = 0.001]. Clinician satisfaction was significantly higher with patients listening to music [82.69(±15.04) vs. 87.3(±15.02) pts.; p = 0.001]. Patient's satisfaction was higher but did not differ significantly. Conclusions: We conclude that self-chosen music contributes objectively to a reduced stress level for patients and therefore subjectively perceived satisfaction for endoscopists. Therefore, music should be considered as a non-pharmacological treatment method of distress reduction especially in the beginning of endoscopic procedures.

[Challenges of the COVID-19 pandemic in gastrointestinal endoscopy: expectations and implementation of recommendations]. / Gastrointestinale Endoskopie in Zeiten der COVID-19-Pandemie: Umsetzung von Empfehlungen und Erwartungen für die Zukunft.

INTRODUCTION: The COVID-19 pandemic represents a major challenge for health care systems worldwide. Recent data suggests an increased risk for personnel of gastrointestinal (GI) endoscopy units for SARS-CoV-2 infections. Several societies have provided recommendations for the current situation, but their feasibility is unclear and real-world data on preparedness of endoscopy units are lacking. AIMS & METHODS: A web-based survey among German GI-endoscopy heads was conducted from April 1 to April 7, 2020. It comprised 33 questions based on the ESGE (European Society of Gastrointestinal Endoscopy) recommendations and was distributed electronically by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). RESULTS: Of 551 completed surveys, 202 (37 %) endoscopy units cancelled less than 40 % of their procedures. Small-volume units (< 4000 procedures/year) cancelled significantly less procedures than high-volume units (> 4000). Complete spatial separation of high-risk patients was possible in only 17 %. Most units systematically identified patients at risk (91 %) and used risk adapted personal protective equipment (PPE, 85 %). For the future, shortages in PPE (83 %), staff (69 %) and relevant financial losses (80 %) were expected. CONCLUSIONS: Recommendations on structural measures were only partially fulfilled and cancellations of procedures were heterogeneous. Clear definitions of indications to perform endoscopies during such a pandemic are needed. Further, structural recommendations should be adapted and strategies to compensate financial losses need to be developed.

German bronchoscopy unit readiness for the COVID-19 pandemic: a nationwide survey.

BACKGROUND: The worldwide impact of the coronavirus disease 2019 (COVID-19) pandemic is unprecedented. Among the aerosol generating procedures, bronchoscopy in particular is an indispensable diagnostic and therapeutic tool that comes with a high risk of infection. Therefore, national societies have issued guidance statements. However, the individual ability of bronchoscopy units to follow these recommendations is largely unknown. METHODS: We conducted a nationwide survey from 1 April 2020 to 7 April 2020 to which 218 German endoscopy units, 105 solely bronchoscopy and 113 interdisciplinary, responded. The survey was distributed electronically via the German Respiratory Society. RESULTS: While 17% of units did not cancel any interventions, 16% cancelled >80% of their interventions. 73% were unable to completely separate high-risk patients. Most procedural measures, such as risk stratification in patients (95%), training to handle COVID-19 patients and personal protective equipment (PPE) (91%), risk adapted use of PPE (85%) and self-monitoring for staff (84%) were adopted well. Unit managers expected shortages in PPE (74%), staff shortages (68%) and severe financial losses (63%). CONCLUSION: In the short-term, PPE shortages are perceived to be the most imminent threat to bronchoscopic activity as a whole. In this era of uncertainty, sound evidence to guide bronchoscopy units and an international concerted effort are urgently needed to formulate recommendations on facts and adapted to local conditions as described in this study.