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Light-based gamma entrainment using sensory stimuli (GENUS) shows considerable potential for the treatment of Alzheimer's disease (AD) in both animal and human models. While the clinical efficacy of GENUS for AD is paramount, its effectiveness will eventually also rely on the barrier to treatment adherence imposed by the discomfort of gazing at luminance flickering (LF) light. Currently, there have been few attempts to improve the comfort of GENUS. Here we investigate if Invisible spectral flicker (ISF), a novel type of light-based 40 Hz GENUS for which the flicker is almost imperceptible, can be used as a more comfortable option. We found that whereas ISF, LF, and chromatic flicker (CF) all produce a 40 Hz steady-state visually evoked potential (SSVEP), ISF scores significantly better on measures of comfort and perceived flicker. We also demonstrate that, while there is a trend towards a lower SSVEP response, reducing the stimulation brightness has no significant effect on the 40 Hz SSVEP or perceived flicker, though it significantly improves comfort. Finally, there is a slight decrease in the 40 Hz SSVEP response when stimulating with ISF from increasingly peripheral angles. This may ease the discomfort of GENUS treatment by freeing patients from gazing directly at the light., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Additional information: The initiators of this project are TSA and PMP. The project has not received any funding. TSA declares that he has no conflict of interest. PMP owns shares in the company OptoCeutics ApS. MHC is CTO and owns shares in the company OptoCeutics ApS. LSH is a full-time employee of OptoCeutics ApS, but initiated the work while at DTU Photonics. MAH is an industrial Ph.D. student enrolled at DTU Compute and partially funded by OptoCeutics ApS and the Innovation Fund Denmark (Case number: 1044-00177A). Both LSH and MAH have stock options in the company OptoCeutics ApS. MTS had a student research position at OptoCeutics ApS, however, he conducted his work while being a Master’s student at DTU. NMN is CEO and owns shares in the company OptoCeutics ApS. JEB owns shares in the company OptoCeutics ApS., (© 2024. The Author(s).)

Background: Modifiable lifestyle factors exert a substantial influence on the development of various diseases. The COVID-19 pandemic necessitated the implementation of containment measures to mitigate the viral spread, which affected the maintenance of healthy habits., Methods: Changes in lifestyle factors (e.g. physical activity, nutrition, smoking, drinking alcohol) within a cohort of German women at increased risk of breast cancer (BC) or ovarian cancer (OC) were evaluated through an anonymous web-based survey. The self-reported assessment of mental health was conducted using the PHQ-4 questionnaire. This tool combines two items from the Patient Health Questionnaire for Depression (PHQ-2) and two queries from the Generalized Anxiety Disorder Scale (GAD-2). Potential predictors of lifestyle changes were determined via multiple logistic regression analysis. A heuristic model was employed to project potential long-term consequences on BC incidence., Results: During the pandemic, 41.6 % of respondents reported reduced engagement in physical activity (PA), whereas 14.3 % reported increased engagement in PA. A score ≥5 on the PHQ-2 scale emerged as an independent risk factor for reduced PA (OR 12.719; 95 % CI 1.089-148.549; p = 0.043). By the heuristic approach, we projected an increase of BC by 3384 cases in Germany by 2030, which is attributable to the alterations in PA patterns during the pandemic., Discussion: Impaired mental health during the pandemic constituted a risk factor for unfavorable changes in PA. Consequently, a surge in BC may arise due to decreased engagement in PA. Healthcare professionals must remain aware of the potential risk factors that facilitate adverse alterations in modifiable risk factors caused by pandemic-related contingency measures or similar future events., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Roxana Schwab reports a relationship with 10.13039/100004337Roche Pharma Schweiz AG Reinach that includes: non-financial support, speaking and lecture fees, and travel reimbursement. Roxana Schwab reports a relationship with 10.13039/100004325AstraZeneca AB that includes: non-financial support, speaking and lecture fees, and travel reimbursement. Roxana Schwab reports a relationship with 10.13039/100009947Merck Sharp & Dohme Corp that includes: speaking and lecture fees. Roxana Schwab reports a relationship with 10.13039/100019944Sanofi-Aventis Deutschland GmbH that includes: non-financial support, speaking and lecture fees, and travel reimbursement. Kathrin Stewen reports a relationship with 10.13039/100019944Sanofi-Aventis Deutschland GmbH that includes: speaking and lecture fees and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100004325AstraZeneca AB that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/501100022274Daiichi Sankyo Inc that includes: consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/501100003769Eisai Inc that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100004312Eli Lilly and Company that includes: board membership, consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100009947Merck Sharp & Dohme Corp that includes: board membership, consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100008792Novartis Pharma AG that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with Pantarhei Bioscience BV that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100004319Pfizer Inc that includes: board membership, consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100004337Roche that includes: board membership, consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100020124Seagen Inc that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100004328Genentech Inc that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with Palleos Healthcare that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt reports a relationship with 10.13039/100013226Pierre Fabre SA that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Annette Hasenburg reports a relationship with 10.13039/100004325AstraZeneca AB that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Annette Hasenburg reports a relationship with 10.13039/100006436Celgene GmbH that includes: consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Annette Hasenburg reports a relationship with GSK that includes: board membership, consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Annette Hasenburg reports a relationship with 10.13039/100004319Pfizer Pharma GmbH that includes: consulting or advisory, funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Annette Hasenburg reports a relationship with Tesaro Bio Germany GmbH that includes: board membership, consulting or advisory, non-financial support, speaking and lecture fees, and travel reimbursement. Katrin Almstedt reports a relationship with 10.13039/100004337Roche Pharma Schweiz AG Reinach that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Katrin Almstedt reports a relationship with 10.13039/100004319Pfizer Pharma GmbH that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Katrin Almstedt reports a relationship with 10.13039/100004325AstraZeneca 10.13039/100024877AB that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Anne-Sophie Heimes reports a relationship with 10.13039/100004319Pfizer Pharma GmbH that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Anne-Sophie Heimes reports a relationship with 10.13039/100004337Roche Pharma AG that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Anne-Sophie Heimes reports a relationship with 10.13039/501100022274Daiichi Sankyo Inc that includes: funding grants, non-financial support, speaking and lecture fees, and travel reimbursement. Marcus Schmidt has patent #EP 2390370 B1 licensed to Licensee. Marcus Schmidt has patent #EP 2951317 B1 licensed to Licensee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

N-alkanes offer a promising approach for assessing the nutritional contribution of external sources to the diets of laying hens in free-range production systems. However, traditional laboratory methods, involving extraction, purification and gas chromatographic analysis, are both economically burdensome and time-consuming. Near-infrared spectroscopy (NIRS) is emerging as a viable alternative, with varying degrees of accuracy depending on the chemical nature and concentration of the component of interest. In our research, we focus on the accuracy of NIRS in predicting the concentrations of n-alkanes (C25-C33) in excreta under simulated free-range conditions with two different diets: one containing a commercial feed with minimal n-alkane content and another containing 1% alfalfa on top of the commercial feed. Spectra processing and calibration were tailored for each n-alkane, with NIRS performance influenced by diet type. Notably, plant predictions using NIR-generated data were consistent with laboratory results, despite a slight tendency toward overestimation (3.40% using the NIRS-generated C25-C29-C33 combination versus 2.80% using laboratory analysis). This indicates the potential of NIRS as an efficient tool to assess n-alkanes in excreta of laying hens and, consequently, the nutritional contribution of the free-range environment, providing rapid and cost-effective results.

The shift in animal welfare standards towards free-range housing for laying hens in the EU has raised questions about changes in dietary composition. Accurate assessment of outdoor plant material intake is crucial for effective feeding strategies. This study introduces an approach using n-alkanes as markers to determine plant intake in laying hens, involving n-alkane recovery rate assessment, discriminant analysis and linear equation-solving for both qualitative and quantitative assessment, respectively, considering systematic n-alkane combinations. Two diets: a standard commercial diet and a diet incorporating 1% alfalfa were tested. Chemical analyses showed an altered n-alkane profile due to alfalfa inclusion, resulting a recovery rates ranging from 30-44% depending on the n-alkane type and diet. Statistical analysis revealed significant differences in recovery rates among the different alkanes for the same diets and between the diets for the same alkane, together with an interaction between n-alkane carbon chain length and initial concentration in the diet. The method accurately predicted plant inclusion, with a slight overestimation (2.80%) using the combination C25-C29-C33. Accurate qualitative classification of the animals based on fecal n-alkanes profiles was observed. The study successfully demonstrated the utility of n-alkanes for estimating dietary composition, providing a non-invasive approach for future free-range studies.

Objective: To provide a composite endpoint in pancreatic surgery., Summary Background Data: Single endpoints in prospective and randomized studies have become impractical due to their low frequency and the marginal benefit of new interventions., Methods: Data from prospective studies were used to develop (n=1273) and validate (n=544) a composite endpoint based on postoperative pancreatic fistula, post-pancreatectomy hemorrhage as well as reoperation and reinterventions. All patients had pancreatectomies of different extents. The association of the developed PAncreatic surgery Composite Endpoint (PACE) with prolonged length of hospital stay (LOS) >75th percentile and mortality was assessed. A single-institution database was used for external validation (n = 2666). Sample size calculations were made for single outcomes and the composite endpoint., Results: In the internal validation cohort, the PACE demonstrated an AUC of 78.0%, a sensitivity of 90.4% and a specificity of 67.6% in predicting a prolonged LOS. In the external cohort, the AUC was 76.9%, the sensitivity 73.8% and the specificity 80.1%. The 90-day mortality rate was significantly different for patients with a positive versus a negative PACE both in the development and internal validation cohort (5.1% vs 0.9%; P< 0.001), as well as in the external validation cohort (8.5% vs 1.2%, P< 0.001). The PACE enabled sample size reductions of up to 80.5% compared to single outcomes., Conclusion: The PACE performed well in predicting prolonged hospital stays and can be used as a standardized and clinically relevant endpoint for future prospective trials enabling lower sample sizes and therefore improved feasibility compared to single outcome parameters., Competing Interests: The authors report no conflicts of interest, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: With an increase in robot-assisted surgery across all specialties, adequate training and credentialing strategies need to be identified to ensure patients safety. The meta-analysis assesses the transferability of technical surgical skills between laparoscopic surgery, open surgery, and robot-assisted surgery., Design: A systematic search was conducted in Medline, Cochrane Central Register of Controlled Trials, and Web of Science. Outcomes were categorized into time, process, product, and composite outcome measures and pooled separately using Hedges'g (standardized mean difference [SMD]). Subgroup analyses were performed to assess the effect of study design, virtual reality platforms and task difficulty., Results: Out of 14,120 screened studies, 30 were included in the qualitative synthesis and 26 in the quantitative synthesis. Technical surgical skill transfer was demonstrated from laparoscopic to robot-assisted surgery (composite: SMD 0.40, 95%-confidence interval [CI] [0.19; 0.62], time: SMD 0.62, CI [0.33; 0.91]) and vice versa (composite: SMD 0.66, CI [0.33; 0.99], time [basic skills]: SMD 0.36, CI [0.01; 0.72]). No skill transfer was seen from open to robot-assisted surgery with limited available data., Conclusion: Technical surgical skills can be transferred from laparoscopic to robot-assisted surgery and vice versa. Robot-assisted and laparoscopic surgical skills training and credentialing should not be regarded separately, but a reasonable combination could shorten overall training times and increase efficiency. Previous experience in open surgery should not be considered as an imperative prerequisite for training in robot-assisted surgery. Recommendations for studies assessing skill transfer are proposed to increase comparability and significance of future studies., Prospero Registration Number: PROSPERO CRD42018104507., (© 2023 The Authors. World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Initial learning curves are potentially shorter in robotic-assisted surgery (RAS) than in conventional laparoscopic surgery (LS). There is little evidence to support this claim. Furthermore, there is limited evidence how skills from LS transfer to RAS., Methods: A randomized controlled, assessor blinded crossover study to compare how RAS naïve surgeons (n = 40) performed linear-stapled side-to-side bowel anastomoses in an in vivo porcine model with LS and RAS. Technique was rated using the validated anastomosis objective structured assessment of skills (A-OSATS) score and the conventional OSATS score. Skill transfer from LS to RAS was measured by comparing the RAS performance of LS novices and LS experienced surgeons. Mental and physical workload was measured with the NASA-task load index (NASA-Tlx) and the Borg-scale., Outcomes: In the overall cohort, there were no differences between RAS and LS for surgical performance (A-OSATS, time, OSATS). Surgeons that were naïve in both LS and RAS had significantly higher A-OSATS scores in RAS (Mean (Standard deviation (SD)): LS: 48.0 ± 12.1; RAS: 52.0 ± 7.5); p = 0.044) mainly deriving from better bowel positioning (LS: 8.7 ± 1.4; RAS: 9.3 ± 1.0; p = 0.045) and closure of enterotomy (LS: 12.8 ± 5.5; RAS: 15.6 ± 4.7; p = 0.010). There was no statistically significant difference in how LS novices and LS experienced surgeons performed in RAS [Mean (SD): novices: 48.9 ± 9.0; experienced surgeons: 55.9 ± 11.0; p = 0.540]. Mental and physical demand was significantly higher after LS., Conclusion: The initial performance was improved for RAS versus LS for linear stapled bowel anastomosis, whereas workload was higher for LS. There was limited transfer of skills from LS to RAS., (© 2023. The Author(s).)

Purpose: Despite the growing understanding of the carcinogenesis of pelvic high-grade serous carcinoma (HGSC) of the ovary and peritoneum and its precursor lesion serous tubal intraepithelial carcinoma (STIC), evidence-based proven recommendations on the clinical management of patients with STIC are lacking so far., Methods: A questionnaire containing 21 questions was developed to explore the clinical experience with patients with the diagnosis of STICs and the diagnostic, surgical and histopathological approaches in Germany. Overall, 540 clinical heads of department in all German gynaecological centres were asked to participate., Results: 131 questionnaires (response rate 24.3%) were included in this survey. 45.8% of the respondents had treated one to three STIC patients during their career. 75.6% of the respondents performed opportunistic bilateral salpingectomies during other gynaecological surgeries. Most of the participants (31.3%) started with the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol in 2014. It was requested by 39.7% centres for prophylactic salpingectomies, by 13.7% for both prophylactic and opportunistic salpingectomies and by 22.1% for neither of both. 38.2%, 1.5% and 24.4% of the participants would use the laparoscopic, transverse and midline laparotomic approach for a surgical staging procedure, respectively. 25.6% (54.7%) of the respondents recommended a hysterectomy in premenopausal (versus postmenopausal) patients with a STIC, 24.4% (88.4%) a bilateral oophorectomy and 50.0% (4.7%) an affected side oophorectomy (all p values < 0.001). Omentectomy, pelvic and para-aortic lymphadenectomy would be performed by 60.5% (64.0%), 9.3% (11.6%) and 9.3% (11.6%) of respondents in premenopausal (versus postmenopausal) patients (all p values > 0.05)., Conclusion: Our survey highlights significant inconsistency in the management of patients with STIC. Prospective data are urgently needed to elucidate the clinical impact of a STIC lesion and its clinical management., (© 2023. The Author(s).)

Fatigue is a very common side effect during intravenous chemotherapy. Unfortunately, only few effective therapeutic options are available, mostly based on daily activity. In our pilot trial we were able to demonstrate that intermittent fasting can reduce fatigue in healthy people, thus we aimed to assess the effects of the fasting dietary on quality of life during chemotherapy in patients with gynecological cancer, especially on the domain of fatigue. The IFAST trial is designed as a prospective, randomized-controlled, multi-center trial. Participation will be offered to women with gynecological cancers (breast cancer, ovarian cancer including peritoneal and fallopian tube cancers, endometrial cancer and cervical cancer) who are planned to receive intravenous chemotherapy for at least three months. Eligible patients will be randomized 1:1, stratified by tumor type and study center. Primary endpoint is the difference in mean change in fatigue, assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT- FS © ). Exploratory secondary endpoints will include general Quality of Life impairment, tolerance of chemotherapy, immunological changes, peripheral cell damage in blood cells, as well as tumor response to chemotherapy. There is new evidence that prolonged fasting periods of 46-96 hours during chemotherapy can positively influence the quality of life during chemotherapy. However, these fasting regiments are not feasible for many patients. Intermittent fasting could be a feasible (manageable) option for many patients to actively improve their quality of life and tolerance to chemotherapy and possibly even enhance the effectiveness of chemotherapy., Trial Registration: https://drks.de, identifier DRKS00031429., Competing Interests: MB reports honoraria and expenses from Pharma Mar AG, Astra Zeneca, TesaroBio GmbH, GSK, Roche, Clovis Oncology and consultant activity to AstraZeneca, Clovis Oncology, Eisai, GSK, MSD, PharmaMar, Roche and Tesaro Bio GmbH. Furthermore, he has received research funding by AstraZeneca, Clovis Oncology, MSD, Eisai and Novartis. None were related to this study. MS reports personal fees from AstraZeneca, BioNTech, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre-Fabre, and Roche. Travel reimbursement from Pfizer and Roche. In addition, M.S. has a patent for EP 2390370 B1 issued and a patent for EP 2951317 B1 issued. AH reports honoraria and expenses from AstraZeneca, Celgen, Leo Pharma, MedConcept GmbH, Med update GmbH, Medpublico GmbH, Pfizer, PharmaMar GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG, Tesaro Bio Germany GmbH as well as work as a consultant to MSD SHARP & DOHME GmbH, PharmaMar, Medpublico GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG and Tesaro Bio Germany GmbH. None were related to this study. RS reports honoraria and expenses from Roche Pharma AG and AstraZeneca GmbH. SS reports honoraria from Lilly, Eisai, and Pfizer as well as expenses from Kite Gilead, all outside of this trial. KAn reports paid lectures by Clovis Oncology, AstraZeneca, Pharma Mar, MSD and Eisai not related to this trial. KAl received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH, Seagen, Med publico GmbH and AstraZeneca not related to the current work. All author authors report no conflict of interest. BB-S reports honoraria from Seagen and MSD not related to this trial. ALe reports honoraria from Astra Zeneca and Roche not related to this trial. SK received speaker honoraria from Roche Pharma AG and Novartis Pharma GmbH Germany, research funding from Novartis Pharma GmbH Germany and travel reimbursement from PharmaMar and Novartis Pharma GmbH Germany, non-related to this trial. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schmidt, Brenner, Gebhard, Schmidt, Singer, Weidenbach, Hahn, Puzankova, Blau-Schneider, Lehnert, Battista, Almstedt, Lütkemeyer, Radsak, Mähringer-Kunz, Krajnak, Linz, Schwab, Gabriel, Hasenburg and Anic.)

Introduction:  Minimally invasive surgery skill laboratories are indispensable in training, especially for complex procedural skills such as intracorporal suturing and knot tying (ICKT). However, maintaining a laboratory is expensive, and specially trained teachers are in short supply. During the COVID-19 pandemic, in-person instruction has reduced to almost zero, while model learning via video instruction (VID) has become an integral part of medical education. The aim of this study was to compare the learning effectiveness and efficiency of ICKT by laparoscopically inexperienced medical students through video versus direct expert instruction., Materials and Methods:  A secondary analysis of two randomized controlled trials was performed. We drew data from students who were trained in ICKT with expert instruction (EXP, n  = 30) and from students who were trained via VID, n  = 30). A laparoscopic box trainer including laparoscope was used for ICKT. Objective Structured Assessment of Technical Skills (OSATS), knot quality, and total ICKT time were the parameters for the assessment in this study. Proficiency criteria were also defined for these parameters., Results:  Students in the EXP group performed significantly better in OSATS-procedure-specific checklist (PSC) and knot quality compared with students in the VID group, with no difference in task time. Of the students who reached the proficiency criteria for OSATS-PSC and knot quality, those in the EXP group required fewer attempts to do so than those in the VID group. Students in both groups improved significantly in all parameters over the first hour of evaluation., Conclusion:  For the laparoscopically inexperienced, training in ICKT through expert instruction presents an advantage compared with video-based self-study in the form of faster understanding of the procedure and the associated consistent implementation of good knot quality. Both teaching methods significantly improved participants' ICKT skills., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed., Methods: Models of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying., Results: In the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1-5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on -2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on -2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7)., Conclusion: The biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Frailty is a frequent and underdiagnosed multidimensional age-related syndrome, involving decreased physiological performance reserves and marked vulnerability against major stressors. To standardize the preoperative frailty assessment and identify patients at risk of adverse surgical outcomes, commonly used global health assessment tools were evaluated. We aimed to assess three interdisciplinary preoperative screening assessments to investigate the influence of frailty status with in-hospital complications irrespective of surgical complexity and radicality in older women with ovarian cancer (OC)., Methods: Preoperative frailty status was examined by the G8 geriatric screening tool (G8 Score-geriatric screening), Eastern Cooperative Oncology Group performance status (ECOG PS-oncological screening), and American Society of Anesthesiologists Physical Status System (ASA PS-anesthesiologic screening). The main outcome measures were the relationship between perioperative laboratory results, intraoperative surgical parameters and the incidence of immediate postoperative in-hospital complications with the preoperative frailty status., Results: 116 consecutive women 60 years and older (BMI 24.8 ± 5.2 kg/m 2 ) with OC, who underwent elective oncological surgery in University Medical Center Mainz between 2008 and 2019 were preoperatively classified with the selected global health assessment tools as frail or non-frail. The rate of preoperative anemia (hemoglobin ≤ 12 g/dl) and perioperative transfusions were significantly higher in the G8-frail group (65.9% vs. 34.1%; p = 0.006 and 62.7% vs. 41.8%, p = 0.031; respectively). In addition, patients preoperatively classified as G8-frail exhibited significantly more postoperative clinical in-hospital complications (27.8% vs. 12.5%, p = 0.045) independent of chronological age and BMI. In contrast, ECOG PS and ASA PS did not predict the rates of postoperative complications (all p values > 0.05). After propensity score matching, the complication rate in the G8-frail cohort was approximately 1.7 times more common than in the G8-non-frail cohort., Conclusion: Preoperative frailty assessment with the G8 Score identified elderly women with OC recording a significantly higher rate of postoperative in-hospital complications. In G8-frail patients, preoperative anemia and perioperative transfusions were significantly more recorded, regardless of chronological age, abnormal BMI and surgical complexity. Standardized preoperative frailty assessment should be added to clinical routine care to enhance risk stratification in older cancer individuals for surgical patient-centered decision-making., (© 2022. The Author(s).)

Background: Many training curricula were introduced to deal with the challenges that minimally invasive surgery (MIS) presents to the surgeon. Situational awareness (SA) is the ability to process information effectively. It depends on general cognitive abilities and can be divided into three steps: perceiving cues, linking cues to knowledge and understanding their relevance, and predicting possible outcomes. Good SA is crucial to predict and avoid complications and respond efficiently. This study aimed to introduce the concept of SA into laparoscopic training., Methods: This is a prospective, randomized, controlled study conducted at the MIS Training Center of Heidelberg University Hospital. Video sessions showing the steps of the laparoscopic cholecystectomy (LC) were used for cognitive training. The intervention group trained SA with interposed questions inserted into the video clips. The identical video clips, without questions, were presented to the control group. Performance was assessed with validated scores such as the Objective Structured Assessment of Technical Skills (OSATS) during LC., Results: 72 participants were enrolled of which 61 were included in the statistical analysis. The SA-group performed LC significantly better (OSATS-Score SA: 67.0 ± 11.5 versus control: 59.1 ± 14.0, p value = 0.034) and with less errors (error score SA: 3.5 ± 1.9 versus control: 4.7 ± 2.0, p value = 0.027). No difference in the time taken to complete the procedure was found. The benefit assessment analysis showed no difference between the groups in terms of perceived learning effect, concentration, or expediency. However, most of the control group indicated retrospectively that they believed they would have benefitted from the intervention., Conclusion: This study suggests that video-based SA training for laparoscopic novices has a positive impact on performance and error rate. SA training should thus be included as one aspect besides simulation and real cases in a multimodal curriculum to improve the efficiency of laparoscopic surgical skills training., (© 2023. The Author(s).)

Aims: The aim of this study was to investigate whether shifting the focus to solution orientation and developing coping strategies for common errors could increase the efficiency of laparoscopic training and influence learning motivation. The concept of coping has been particularly defined by the psychologist Richard Lazarus [Lazarus and Folkman in Stress, appraisal, and coping, Springer publishing company, New York, 1984]. Based on this model, we examined the use of observational learning with a coping model for its effectiveness as a basic teaching model in laparoscopic training., Methods: 55 laparoscopically naive medical students learned a standardized laparoscopic knot tying technique with video-based instructions. The control group was only offered a mastery video that showed the ideal technique and was free from mistakes. The intervention group was instructed on active error analysis and watched freely selectable videos of common errors including solution strategies (coping model) in addition to the mastery videos., Results: There was no statistically significant difference between the intervention and control groups for number of knot tying attempts until proficiency was reached (18.8 ± 5.5 vs. 21.3 ± 6.5, p = 0.142). However, there was a significantly higher fraction of knots achieving technical proficiency in the intervention group after first use of the coping model (0.7 ± 0.1 vs. 0.6 ± 0.2, p = 0.026). Additionally, the proportion of blinded attempts that met the criteria for technical proficiency was significantly higher for the intervention group at 60.9% vs. 38.0% in control group (p = 0.021). The motivational subscore "interest" of the validated score on current motivation (QCM) was significantly higher for the intervention group (p = 0.032), as well as subjective learning benefit (p = 0.002) and error awareness (p < 0.001)., Conclusion: Using video-based learning of coping strategies for common errors improves learning motivation and understanding of the technique with a significant difference in its qualitative implementation in laparoscopy training. The ability to think in a solution-oriented, independent way is necessary in surgery in order to recognize and adequately deal with technical difficulties and complications., (© 2023. The Author(s).)

Introduction: Metronomic chemotherapy (MCT) is increasingly used in oncology due to its favorable therapeutic index. There is still a lack of evidence for MCT in metastatic breast cancer (MBC). In this retrospective unicenter study, we demonstrated real-word data on MCT in MBC., Methods: MBC patients who received metronomic oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day), CTX and capecitabine (CAPE) (500 mg thrice daily), CTX, or vinorelbine (VRL) (30 mg daily) alone for at least 4 weeks between 2009 and 2021 were included. The primary endpoint was disease control rate (DCR) ≥24 weeks. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patient characteristics and therapy response were analyzed using χ 2 test. For survival analyses, Kaplan-Meier estimator and log-rank test were used., Results: Seventy-two patients were identified. Sixty-two patients received CTX/MTX, three CTX/CAPE, two CTX, and five VRL. Median age at diagnosis MBC and at start of MCT was 59.0 years and 64.5 years, respectively. 72.2% tumors were hormone receptor positive and 27.8% were triple-negative. 54.2% patients had more than two different metastases. 80.6% patients showed visceral involvement. 31.9% patients achieved DCR ≥24 weeks. Median PFS was 17.0 weeks (95% CI 14.5-19.5) and median OS was 58.0 weeks (95% CI 29.0-87.0). MCT showed similar DCR ≥24 weeks and clinically meaningful but not statistically significant shorter median PFS compared to prior therapy (31.9% versus 32.8% [ p = 0.570] and 17.0 weeks versus 20.0 weeks [ p = 0.093], respectively) and statistically significant higher DCR ≥24 weeks and longer median PFS compared to subsequent therapy (31.9% versus 17.4% [ p = 0.038] and 17.0 weeks versus 12.0 weeks [ p = 0.006], respectively). Three (4.2%) patients terminated MCT because of toxicity., Conclusion: In this real-world retrospective study, MCT was effective and well tolerated and may thus represent a valuable treatment option in selected MBC patients., Competing Interests: Slavomir Krajnak: lecture: Novartis and Roche. Research funding: Novartis. Travel reimbursement: Novartis and PharmaMar. Katharina Anic: lecture: AstraZeneca, Clovis Oncology, and MSD. Katrin Almstedt: lecture: AstraZeneca, Pfizer, and Roche. Anne-Sophie Heimes: lecture: Medupdate GmbH, Pfizer, and Roche. Annette Hasenburg: advisory board: AstraZeneca, GSK, LEO Pharma, MSD, PharmaMar, Roche, and Tesaro. Lecture: AstraZeneca, Celgene, Clovis Oncology, LEO Pharma, MedConcept GmbH, Med update GmbH, Medicultus, Pfizer, PharmaMar, Roche, Streamedup! GmbH, and Tesaro. Marcus Schmidt: lecture: AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen. Research funding: AstraZeneca, BioNTech, Eisai, Genentech, Novartis, Pantarhei Bioscience, Pfizer, Pierre-Fabre, Roche, and SeaGen. Travel reimbursement: Pfizer and Roche. Marco Johannes Battista: advisory board: Eisai, GSK, MSD, PharmaMar, Roche, and Tesaro. Lectures: Astra Zeneca, Clovis Oncology, GSK, MSD, PharmaMar, Roche, and Tesaro. Research funding: AstraZeneca, Clovis Oncology, MSD, and Novartis. All other authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

Objective: Five commonly used global health assessment tools have been evaluated to identify and assess the preoperative frailty status and its relationship with perioperative in-hospital complications and transfusion rates in older women with endometrial cancer (EC)., Methods: Preoperative frailty status was examined by the G8 questionnaire, the Eastern Cooperative Oncology Group performance status, the Charlson Comorbidity Index and the American Society of Anesthesiologists Physical Status System, as well as the Lee-Schonberg prognostic index. The main outcome measures were perioperative laboratory values, intraoperative surgical parameters and immediately postoperative complications., Results: 153 consecutive women ≥ 60 years with all stages of EC, who received primary elective surgery at the University Medical Center Mainz between 2008 and 2019 were classified with selected global health assessment tools according to their preoperative performance status. In contrast to conventional prognostic parameters like older age and higher BMI, increasing frailty was significantly associated with preoperative anemia and perioperative transfusions (p < 0.05). Moreover, in patients preoperatively classified as frail significantly more postoperative complications (G8 Score: frail: 20.7% vs. non-frail: 6.7%, p = 0.028; ECOG: frail: 40.9% vs. non-frail: 2.8%, p = 0.002; and CCI: frail: 25.0% vs. non-frail: 7.4%, p = 0.003) and an increased length of hospitalization were recorded. According to propensity score matching, the risk for developing postoperative complications for frail patients was approximately two-fold higher, depending on which global health assessment tool was used., Conclusions: Preoperatively assessed frailty significantly predicts post-surgical morbidity rates in contrast to conventionally used single prognostic parameters such as age or BMI. A standardized preoperative assessment of frailty in the routine work-up might be beneficial in older cancer patients before major surgery to include these patients in a prehabilitation program with nutrition counseling and physiotherapy to adequately assess the perioperative risk., (© 2022. The Author(s).)

Background: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected patients with early vulvar cancer. This study aimed to assess current management practices with respect to the sentinel node procedure in women with early vulvar cancer in Germany., Methods: A Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments. Data were summarized as frequencies and analyzed using the chi-square test., Results: A total of 222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%, respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management., Conclusions: The majority of German hospitals implement the SN procedure. However, only 79.5% of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest recommendations and clinical evidence. Deviations from state-of-the-art management should only be after a detailed discussion with the concerned patient.

Background: The aim of this study was to assess the transferability of surgical skills for the laparoscopic hernia module between the serious game Touch Surgery™ (TS) and the virtual reality (VR) trainer Lap Mentor™. Furthermore, this study aimed to collect validity evidence and to discuss "sources of validity evidence" for the findings using the laparoscopic inguinal hernia module on TS., Methods: In a randomized crossover study, medical students (n = 40) in their clinical years performed laparoscopic inguinal hernia modules on TS and the VR trainer. TS group started with "Laparoscopic Inguinal Hernia Module" on TS (phase 1: Preparation, phase 2: Port Placement and Hernia Repair), performed the module first in training, then in test mode until proficiency was reached. VR group started with "Inguinal Hernia Module" on the VR trainer (task 1: Anatomy Identification, task 2: Incision and Dissection) and also performed the module until proficiency. Once proficiency reached in the first modality, the groups performed the other training modality until reaching proficiency. Primary endpoint was the number of attempts needed to achieve proficiency for each group for each task/phase., Results: Students starting with TS needed significantly less attempts to reach proficiency for task 1 on the VR trainer than students who started with the VR trainer (TS = 2.7 ± 0.6 vs. VR = 3.2 ± 0.7; p = 0.028). No significant differences for task 2 were observed between groups (TS = 2.3 ± 1.1 vs. VR = 2.1 ± 0.8; p = 0.524). For both phases on TS, no significant skill transfer from the VR trainer to TS was observed. Aspects of validity evidence for the module on TS were collected., Conclusion: The results show that TS brought additional benefit to improve performances on the VR trainer for task 1 but not for task 2. Skill transfer from the VR trainer to TS could not be shown. VR and TS should thus be used in combination with TS first in multimodal training to ensure optimal training conditions., (© 2022. The Author(s).)

Purpose: The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival., Methods: Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan-Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters., Results: 153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35-15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31-6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively)., Conclusions: This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity., (© 2022. The Author(s).)

Background: Intermittent fasting (IF) is defined as an eating pattern without calorie restrictions, alternating between periods of fasting and eating. In the past decades IF has not only become a popular weight-reducing diet but is thought to improve Quality of Life (QoL) and fatigue. However, very little evidence exists for the general population. Thus, we aimed to assess the impact of a 16-h fasting period per day over a three-month study period on QoL and especially fatigue in healthy people. Methods: We conducted a prospective cohort study including healthy subjects. All participants fasted 16 h for at least five days a week while maintaining their normal lifestyle. In the study, we analysed blood samples as well as QoL through standardized questionnaires (WHO-5 questionnaire, Short Form Health 36). Furthermore, we measured the degree of fatigue with the Fatigue Assessment Scale (FAS) and Fatigue Severity Scale (FSS) as well as compliance, activity records, and weight alterations. All endpoints were evaluated at baseline, after two weeks, four weeks, and three months of IF. Results: A total of 30 participants fasted for the entire study period. The results of the WHO-5 questionnaire (15.6 ± 4.6 vs. 18 ± 3.6, p < 0.0019) demonstrated a significant increase in QoL. For long-term QoL six out of eight domains measured by the Short Form Health 36 (SF-36) significantly improved (e.g., physical health: 92.3 ± 11.6 vs. 96.5 ± 6.3, p = 0.015; mental health: 75.5 ± 12.0 vs. 81.7 ± 9.0; p < 0.001 and body pain: 74.1 ± 31.8 vs. 89.5 ± 14.9; p = 0.008) after three months. Fatigue significantly decreased from 10.3 ± 3.2 to 8.4 ± 2.5; p = 0.002 for mental fatigue and from 12.6 ± 3.8 to 10.7 ± 3.3; p = 0.002 measured by the FAS. The mean FSS-Score at baseline was 3.5 ± 1.2 compared to 2.9 ± 1.1 (scale 1−7) after three months (p < 0.001). Notably, the proliferation marker IGF-1 was significantly reduced. No clinically significant changes in laboratory parameters were observed that would have endangered a participant’s safety. Conclusions: IF according to the 16:8 regime over a fasting period of three months significantly improved several aspects of the QoL and decreased fatigue in healthy people, while maintaining a good safety profile. The practicability of this diet was also demonstrated for shift workers and people with a high percentage of active labour. Apart from the improvement in QoL and fatigue, the significant reduction in IGF-1, which can act as an accelerator of tumour development and progression, might be an indicator of the potential benefits of IF for patients with cancer.

Aims: In minimally invasive surgery (MIS), intraoperative guidance has been limited to verbal communication without direct visual guidance. Communication issues and mistaken instructions in training procedures can hinder correct identification of anatomical structures on the MIS screen. The iSurgeon system was developed to provide visual guidance in the operating room by telestration with augmented reality (AR)., Methods: Laparoscopic novices (n = 60) were randomized in two groups in a cross-over design: group 1 trained only with verbal guidance first and then with additional telestration with AR on the operative screen and vice versa for group 2. Training consisted of laparoscopic basic training and subsequently a specifically designed training course, including a porcine laparoscopic cholecystectomy (LC). Outcome included time needed for training, performance with Global Operative Assessment of Laparoscopic Skills (GOALS), and Objective Structured Assessment of Technical Skills (OSATS) score for LC, complications, and subjective workload (NASA-TLX questionnaire)., Results: Telestration with AR led to significantly faster total training time (1163 ± 275 vs. 1658 ± 375 s, p &lt; 0.001) and reduced error rates. LC on a porcine liver was performed significantly better (GOALS 21 ± 5 vs. 18 ± 4, p &lt; 0.007 and OSATS 67 ± 11 vs. 61 ± 8, p &lt; 0.015) and with less complications (13.3% vs. 40%, p &lt; 0.020) with AR. Subjective workload and stress were significantly reduced during training with AR (33.6 ± 12.0 vs. 30.6 ± 12.9, p &lt; 0.022)., Conclusion: Telestration with AR improves training success and safety in MIS. The next step will be the clinical application of telestration with AR and the development of a mobile version for remote guidance., (© 2022. The Author(s).)

(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile age. Pain management with analgesics is frequently used by women with endometriosis. During the COVID-19 pandemic, access to health services was temporarily restricted in various countries for persons without serious conditions, resulting in increased physical and mental health issues. The present study was conducted in order to assess the risk factors predicting increased analgesic intake by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale (GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational level (OR 2.719; 95% CI 1.137-6.501; p = 0.025) and being at higher risk for depressive disorders, as measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055-5.450; p = 0.037), were independent risk factors for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI 1.007-1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication. The degree of reduction in social support and in social networks were independent predictors of an increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an increased intake of OTC analgesics was related to a higher educational level and having a depressive disorder, while a higher pain-induced disability was an independent risk factor for an increased intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence an increased intake of analgesics in women with endometriosis during the first wave of the COVID-19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to increased analgesic use in women with endometriosis in order to identify persons at risk for the misuse of pain medication and to prevent potential adverse effects.

Introduction: Perioperative red blood cell (RBC) transfusions have been associated with increased morbidity and worse oncological outcome in some solid neoplasms. In order to elucidate whether RBC transfusions themselves, the preoperative anemia of cancer (AOC), or the impaired global health status might explain this impact on patients with endometrial cancer (EC) or ovarian cancer (OC), we performed a retrospective, single-institution cohort study., Materials and Methods: Women older than 60 years with EC or OC were included. The influence of RBC transfusions, AOC, and frailty status determined by the G8 geriatric screening tool (G8 score), as well as the clinical-pathological cancer characteristics on progression-free survival (PFS) and overall survival (OS), was determined by using the Kaplan-Meier method and the Cox regression analyses., Results: In total, 263 patients with EC (n = 152) and OC (n = 111) were included in the study. Patients with EC receiving RBC transfusions were faced with a significantly shorter 5-year PFS (79.8% vs. 26.0%; p < 0.001) and 5-year OS (82.6% vs. 25.7%; p < 0.001). In multivariable analyses, besides established clinical-pathological cancer characteristics, the RBC transfusions remained the only significant prognostic parameter for PFS (HR: 1.76; 95%-CI [1.01-3.07]) and OS (HR: 2.38; 95%-CI [1.50-3.78]). In OC, the G8 score stratified the cohort in terms of PFS rates (G8-non-frail 53.4% vs. G8-frail 16.7%; p = 0.010) and AOC stratified the cohort for 5-year OS estimates (non-anemic: 36.7% vs. anemic: 10.6%; p = 0.008). Multivariable Cox regression analyses determined the G8 score and FIGO stage as independent prognostic factors in terms of PFS (HR: 2.23; 95%-CI [1.16-4.32] and HR: 6.52; 95%-CI [1.51-28.07], respectively). For OS, only the TNM tumor stage retained independent significance (HR: 3.75; 95%-CI [1.87-7.53])., Discussion: The results of this trial demonstrate the negative impact of RBC transfusions on the prognosis of patients with EC. Contrastingly, the prognosis of OC is altered by the preoperative global health status rather than AOC or RBC transfusions. In summary, we suggested a cumulatively restrictive transfusion management in G8-non-frail EC patients and postulated a more moderate transfusion management based on the treatment of symptomatic anemia without survival deficits in OC patients., Competing Interests: KA reports personal fees from Eisai, Roche, MSD. MWS reports holding a patent WO 2021/176091 A1 not related to this study. SK received speaker Honoria, research funding and travek reimbursement from Vovartis Pharma GmbH Germany. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, MS has a patent for EP 2390370 B1 and a patent for EP 2951317 B1issued. RS reports honoraria and expenses from Roche Pharma AG and AstraZeneca GmbH. AH reports honoraria and expenses from AstraZeneca, FBA Frauenärzte BundesAkademie GmbH, KlarigoVerlag, MedConcept, Med public GmbH, Med update GmbH, Medicultus, Pfizer, Promedicis GmbH, Pierre Fabre Pharma GmbH, Softconsult, Roche Pharma AG, Streamedup! GmbH, Tesaro Bio Germany GmbH. I am consultant to PharmaMar, Promedicis GmbH, Pierre Fabre Pharma GmbH, Roche Pharma AG and Tesaro Bio Germany GmbH. I have received funded research from Celgene. MB reports honoraria and expenses from Pharma Mar, Astra Zeneca, Tesaro, GSK, Roche, Clovis Oncology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Anic, Schmidt, Schmidt, Krajnak, Löwe, Linz, Schwab, Weikel, Brenner, Westphalen, Rissel, Hartmann, Conradi, Hasenburg and Battista.)

Epidural analgesia could influence the postoperative oncologic outcomes in patients with specific types of non-metastatic solid neoplasms. The present study aimed to investigate the impact of anesthetic technique on survival in elderly patients with ovarian cancer (OC). The records of all women with OC older than 60 years of age undergoing tumor debulking surgery at the University Medical Center of the Johannes Gutenberg University Mainz (Mainz, Germany) between January 2008 and December 2019 were obtained. The study cohort was divided into two groups based on the use of perioperative epidural anesthesia or not. First, Kaplan-Meier analysis was performed to analyze the prognostic influence of anesthetic technique on survival. Second, multivariate Cox proportional hazards model was adjusted for multiple conventional prognostic factors concerning three main categories: i) Current clinical-pathological tumor characteristics; ii) anesthesiologic parameters, including mean age, American Society of Anesthesiologists Performance Status and preexisting comorbidities summarized in the Charlson Comorbidity Index; and iii) oncological and surgical parameters such as oncological radicality and Surgical complexity Score. A total of 110 patients were included in the study and 71 (64.5%) of them received epidural analgesia. The median survival time was 26.0 months from primary debulking surgery and no significant differences in progression-free (PFS) and overall survival (OS) were noted between the 'Epidural' and 'non-Epidural' cohorts. After adjustment for the selected risk factors from the three categories, the effects of epidural analgesia on PFS and OS remained non-significant [PFS: hazard ratio (HR), 1.26; 95% CI, 0.66-2.39; and OS: HR, 0.79; 95% CI, 0.45-1.40]. The present results did not support the independent association between epidural-supplemented anesthesia and improved PFS or OS in elderly patients with standardized ovarian cancer debulking surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Anic et al.)

(1) Background: The main aim of this research was to examine the factors leading to pain-induced disability by assessing the impact of demographic, endometriosis-specific, pandemic-specific, and mental health factors. (2) Methods: Women with endometriosis who attended online support groups were invited to respond to an online survey during the first wave of the COVID-19 pandemic in Germany. The Pain Disability Index (PDI) was employed to assess disability-related daily functioning. Independent predictors of pain-induced disability were determined using univariate and multivariate logistic regression analyses. (3) Results: The mean PDI score of the study population was 31.61 (SD = 15.82), which was significantly higher (p < 0.001) than that reported in a previously published normative study of the German population. In the present study, a high level of pain-induced disability, as defined by scores equal to or higher than the median of the study population, older age (OR 1.063, 95% CI 1.010−1.120, p = 0.020), dysmenorrhea (OR 1.015, 95% CI 1.005−1.026, p = 0.005), dysuria (OR 1.014; 95% CI 1.001−1.027, p = 0.029), lower back pain (OR 1.018, 95% CI 1.007−1.029, p = 0.001), and impaired mental health (OR 1.271, 95% CI 1.134−1.425, p < 0.001) were found to be independent risk factors. Pandemic-specific factors did not significantly influence the pain-induced disability of the participants in this study. (4) Conclusions: The level of pain-induced disability was significantly higher among the women with endometriosis than among women in the normative German validation study. Our findings identified risk factors for experiencing a high level of pain-induced disability, such as demographic and specific pain characteristics. Pandemic-specific factors did not significantly and independently influence the pain-induced disability during the first wave of the COVID-19 pandemic in Germany. Impaired mental health negatively influenced functioning during daily activities. Thus, women with endometriosis should be managed by a multidisciplinary team of healthcare professionals to prevent negative effects of pain-induced disability on their quality of life.

Background: Endometriosis is a multifaceted chronic pain disorder that can have an impact on both physical and mental health. Women suffering from chronic pain may be more susceptible to various health disorders, especially during adversity, such as the COVID-19 pandemic. Previous research has identified resilience as a mediator between internal or external stressors and well-being. Methods: An online survey was conducted during the first wave of the COVID-19 pandemic in Germany through patient support groups of women with endometriosis. The Brief Resilience Score (BRS) was employed to evaluate resilience, while the PHQ-4 questionnaire was used to assess self-reported mental health. Univariate and multivariate logistic regression analyses were applied to determine resilience’s independent risk and protective parameters. Results: High educational level was found to be an independent supportive moderator of high resilience in women with a resilience score greater than the study population’s median (BRS > 2.66; OR 2.715; 95% CI 1.472−5.007; p = 0.001) but not in women in the highest resilience score quartile (BRS > 3.33). A decrease in perceived social support was detected to be the most powerful independent risk factor for low resilience: OR 0.541, 95% CI 0.307−0.952, p = 0.033 for predicting BRS > 2.66, and OR 0.397, 95% CI 0.189−0.832, p = 0.014 for predicting scores > 3.33 on the BRS scale. A high burden of mental health symptoms, as measured by the PHQ-4 scale, was negatively associated with resilience. Conclusions: Satisfying social support and good mental health were shown to be key resources for resilience. The results of this study may assist in the identification of women at risk for low resilience and the development of resilience-building strategies in patients with endometriosis.

Introduction: The aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS)., Materials and Methods: The Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted. Video recordings were scored by two blinded raters assessing intrarater and interrater reliability and discriminative abilities between novices (n = 8), intermediates (n = 24), and experts (n = 8)., Results: The Delphi process included 18 international experts and was successfully completed after 4 rounds. A total of 4 relevant main steps as well as 15 substeps were identified and a definition of each substep was provided. A maximum of 75 points could be reached in the unweighted A-OSATS score and 170 points in the weighted A-OSATS score respectively. A total of 41 anastomoses were evaluated. Excellent intrarater (r = 0.807-0.988, p < 0.001) and interrater (intraclass correlation coefficient = 0.923-0.924, p < 0.001) reliability was demonstrated. Both versions of the A-OSATS correlated well with the general OSATS and discriminated between novices, intermediates, and experts defined by their OSATS global rating scale., Conclusion: With the weighted and unweighted A-OSATS score, we propose a new reliable standard to assess the creation of minimally invasive linear-stapled, hand-sewn anastomoses based on an international expert consensus. Validity evidence in live animal models is provided in this study. Future research should focus on assessing whether the weighted A-OSATS exceeds the predictive capabilities of patient outcomes of the unweighted A-OSATS and provide further validity evidence on using the score on different anastomotic techniques in humans., (© 2021. The Author(s).)

Background: Endometriosis is a multifaceted chronic pain condition that can have a negative impact on mental health. Patients suffering from chronic pain may face an additional psychological burden during adversity, such as the COVID-19 pandemic. The main aim of this research was to evaluate the prevalence of self-reported depression and anxiety, the influence of demographic, endometriosis-specific, pandemic-specific factors, and resilience on mental health outcomes of patients with endometriosis. Methods: An online survey was conducted through patient support groups of women suffering from endometriosis during the first wave of the COVID-19 pandemic. The PHQ-4 questionnaire, which combines two items of the Patient Health Questionnaire for Depression (PHQ-2) and two items from the Generalized Anxiety Disorder Scale (GAD-2) was used to assess self-reported mental health. The Brief Resilience Score (BRS) was employed to evaluate resilience. Independent risk and protective factors for mental health were investigated by multivariate logistic regression analyses. Results: The PHQ-4 questionnaire was completed by 274 respondents. More than 40% reached depression (PHQ-2) and anxiety (GAD-2) scores of ≥3, and more than 20% achieved PHQ-2 and GAD-2 scores of ≥5. High resilience was found to be a reliable and strong independent protector for the probability of developing adverse psychological outcomes: OR 0.295, p < 0.001 for developing generalized anxiety disorder (GAD-2 ≥ 3), and OR 0.467, p < 0.001 for having major depression (PHQ-2 ≥ 3). Conclusions: Pain-induced disability is an independent risk factor for developing major depression and anxiety, while resilience was identified as a potential protective parameter in terms of positive psychological outcomes in women with endometriosis. The results of this study may help to identify women at risk for adverse mental health outcomes and should encourage healthcare practitioners to establish strategies for the reduction of negative psychological and psychiatric impacts on patients with endometriosis.

Purpose: To systematically review the current body of evidence on the efficacy and safety of immunotherapy for cervical cancer (CC)., Material and Methods: Medline, the Cochrane Central Register of Controlled Trials and Web of Science were searched for prospective trials assessing immunotherapy in CC patients in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles in English and German reporting outcomes of survival, response rates or safety were eligible., Results: Of 4655 screened studies, 51 were included (immune checkpoint inhibitors (ICI) n =20; therapeutic vaccines n = 25; adoptive cell transfer therapy n =9). Of these, one qualified as a phase III randomized controlled trial and demonstrated increased overall survival following treatment with pembrolizumab, chemotherapy and bevacizumab. A minority of studies included a control group ( n = 7) or more than 50 patients ( n = 15). Overall, response rates were low to moderate. No response to ICIs was seen in PD-L1 negative patients. However, few remarkable results were achieved in heavily pretreated patients. There were no safety concerns in any of the included studies., Conclusion: Strong evidence on the efficacy of strategies to treat recurrent or metastatic cervical cancer is currently limited to pembrolizumab in combination with chemotherapy and bevacizumab, which substantiates an urgent need for large confirmatory trials on alternative immunotherapies. Overall, there is sound evidence on the safety of immunotherapy in CC.

Background: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC)., Methods: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival., Results: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056-3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival., Conclusions: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone., (© 2021 S. Karger AG, Basel.)

Magmas readily react with their wall-rocks forming metamorphic contact aureoles. Sulphur and possibly metal mobilization within these contact aureoles is essential in the formation of economic magmatic sulphide deposits. We performed heating and partial melting experiments on a black shale sample from the Paleoproterozoic Virginia Formation, which is the main source of sulphur for the world-class Cu-Ni sulphide deposits of the 1.1 Ga Duluth Complex, Minnesota. These experiments show that an autochthonous devolatilization fluid effectively mobilizes carbon, sulphur, and copper in the black shale within subsolidus conditions (≤ 700 °C). Further mobilization occurs when the black shale melts and droplets of Cu-rich sulphide melt and pyrrhotite form at ∼1000 °C. The sulphide droplets attach to bubbles of devolatilization fluid, which promotes buoyancy-driven transportation in silicate melt. Our study shows that devolatilization fluids can supply large proportions of sulphur and copper in mafic-ultramafic layered intrusion-hosted Cu-Ni sulphide deposits., (© 2021. The Author(s).)

Background: Endometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lockdown impacted the various aspects of pain perception in a group of chronic pain patients, such as women suffering from endometriosis., Methods: Between 6th to 27th April 2020, an online questionnaire was activated at internet platforms of endometriosis patients support groups. Participants were asked retrospectively at one time point about their visual pain intensity measured by the visual analogue scale (VAS) and pain disability via pain disability index (PDI) prior to initiation of social distancing measures in Germany (VASP, PDIP), as well as the pain intensity and pain disability since implementation of social distancing measures (VASI, PDII). Differences of VAS and PDI previous and after implementation of social distancing measures were displayed as ΔVAS and ΔPDI. Pain experience and social support were assessed by a 5-point Likert scale., Results: 285 participants completed at least one question regarding pain intensity, disability, pain experience or social support. Dysmenorrhea, the symptom with the highest level of pain assessed by VAS, decreased significantly during the SARS-CoV-2 pandemic compared to the time period prior to social isolation (45.30% respondents experienced improvemenet vs 40.50% who experienced worsening; p = 0.025). The global physical impairment improved significantly (improvement of pain induced disability in 48.20% vs 40.90% with worsening of pain symptoms; p = 0.032) after the implementation of social distancing measures. Pain experience was negatively affected by social distancing measures, since frequency of pain awareness increased in 43.6% (p<0.001) of participants and 30.0% (p<0.001) more participants experienced pain as a threat. Verbalization of pain experience was reduced in 36.6% (p = 0.001) of participants and 14.6% (p = 0.91), 21.9% (p<0.001) and 31.5% (p<0.001) of participants reported less social support from their partner, family and friends., Conclusions: Physical pain and disability on one hand and emotional and social pain experience on the other were differentially affected by the emerged emotional, social and health care constraints related to the SARS-CoV-2 pandemic., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RS: Honoraria: Roche Pharma AG, AstraZeneca, Streamedup!GmbH MJB: Honoraria: Roche Pharma AG, Tesaro Bio GmbH, Pharma Mar AG, Astra Zeneca Germany and Clovis Oncology AH: Honoraria: AstraZeneca; Celgen; MedConcept GmbH, Med update GmbH; Medicultus; Pfizer; Promedicis GmbH; Softconsult; Roche Pharma AG; Streamedup!GmbH; Tesaro Bio Germany GmbH, LEO Pharma Ad Board: PharmaMar; Promedicis GmbH; Roche Pharma AG; Tesaro Bio Germany GmbH, AstraZeneca, LEO Pharma, MSD Sharp&Dohme GmbH This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Undifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications., (© 2021. The Author(s).)

Benchmarking calculations on excited states of models of phenylalanine protein chains are presented to assess the ability of alternative methods to the standard and most commonly used multiconfigurational wave function-based method, the complete active space self-consistent field (CASSCF), in recovering the non-dynamical correlation for systems that become not affordable by the CASSCF. The exploration of larger active spaces beyond the CASSCF limit is benchmarked through three strategies based on the reduction in the number of determinants: the restricted active space self-consistent field, the generalized active space self-consistent field (GASSCF), and the occupation-restricted multiple active space (ORMAS) schemes. The remaining dynamic correlation effects are then added by the complete active space second-order perturbation theory and by the multireference difference dedicated configuration interaction methods. In parallel, the approximate second-order coupled cluster (CC2), already proven to be successful for small building blocks of model proteins in one of our previous works [Ben Amor et al., J. Chem. Phys. 148, 184105 (2018)], is investigated to assess its performances for larger systems. Among the different alternative strategies to CASSCF, our results highlight the greatest efficiency of the GASSCF and ORMAS schemes in the systematic reduction of the configuration interaction expansion without loss of accuracy in both nature and excitation energies of both singlet ππ * and nπ * CO excited states with respect to the equivalent CASSCF calculations. Guidelines for an optimum applicability of this scheme to systems requiring active spaces beyond the complete active space limit are then proposed. Finally, the extension of the CC2 method to such large systems without loss of accuracy is demonstrated, highlighting the great potential of this method to treat accurately excited states, mainly single reference, of very large systems.

Background: The recognition, prevention and treatment of venous thromboembolism (VTE) remains a major challenge in the face of the recent COVID-19 pandemic which has been associated with significant cardiovascular, renal, respiratory and hematologic complications related to hypercoagulability. There has been little literature thus far on the utility of screening ultrasound and the role of the clinical pharmacist in treating these patients., Methods: We present a prospective pilot program of thirty-one consecutive COVID-19 patients who were provided four extremity screening ultrasounds for VTE on admission. This was coordinated by a clinical pharmacist as part of a multidisciplinary approach. Quantitative and qualitative data were recorded with the goal of describing the utility of the clinical pharmacist in ultrasound screening. Data collected include demographics, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during the hospitalization from each individual electronic medical record., Results: Nine of the thirty-one patients presented with VTE. Of the nine patients, there were twenty-two total clotted vessels, all of which were asymptomatic. The clinical pharmacist, as the coordinator for a multidisciplinary COVID-19 associated coagulopathy management team, drafted a screening and treatment protocol for anticoagulation prophylaxis and therapy of VTE after ultrasound findings., Conclusion: VTE screening of hospitalized COVID-19 patients reveals a significant number of asymptomatic VTEs and justifies diagnostic, prophylactic, and treatment measures coordinated by a clinical pharmacist.

Objective: To provide an overview of ML models and data streams utilized for automated surgical phase recognition., Background: Phase recognition identifies different steps and phases of an operation. ML is an evolving technology that allows analysis and interpretation of huge data sets. Automation of phase recognition based on data inputs is essential for optimization of workflow, surgical training, intraoperative assistance, patient safety, and efficiency., Methods: A systematic review was performed according to the Cochrane recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Web of Science, IEEExplore, GoogleScholar, and CiteSeerX were searched. Literature describing phase recognition based on ML models and the capture of intraoperative signals during general surgery procedures was included., Results: A total of 2254 titles/abstracts were screened, and 35 full-texts were included. Most commonly used ML models were Hidden Markov Models and Artificial Neural Networks with a trend towards higher complexity over time. Most frequently used data types were feature learning from surgical videos and manual annotation of instrument use. Laparoscopic cholecystectomy was used most commonly, often achieving accuracy rates over 90%, though there was no consistent standardization of defined phases., Conclusions: ML for surgical phase recognition can be performed with high accuracy, depending on the model, data type, and complexity of surgery. Different intraoperative data inputs such as video and instrument type can successfully be used. Most ML models still require significant amounts of manual expert annotations for training. The ML models may drive surgical workflow towards standardization, efficiency, and objectiveness to improve patient outcome in the future., Registration Prospero: CRD42018108907., Competing Interests: Carly Garrow, Karl-Friedrich Kowalewski, Linhong Li, Martin Wagner, Mona Schmidt, Sandy Engelhardt, Hannes Kenngott, Sebastian Bodenstedt, Stefanie Speidel, and Beat Müller-Stich have no conflicts of interest or financial ties to disclose. Felix Nickel reports receiving travel support for conference participation and equipment provided for laparoscopic surgery courses by KARL STORZ, Johnson & Johnson, Intuitive Surgical, Cambridge Medical Robotics, and Medtronic. Daniel Hashimoto serves as an independent consultant for Verily Life Sciences and the Johnson & Johnson Institute. He serves on the clinical advisory board of Worrell, Inc and has received research support from Olympus Corporation. The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The value of virtual reality (VR) simulators for robot-assisted surgery (RAS) for skill assessment and training of surgeons has not been established. This systematic review and meta-analysis aimed to identify evidence on transferability of surgical skills acquired on robotic VR simulators to the operating room and the predictive value of robotic VR simulator performance for intraoperative performance., Methods: MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched systematically. Risk of bias was assessed using the Medical Education Research Study Quality Instrument and the Newcastle-Ottawa Scale for Education. Correlation coefficients were chosen as effect measure and pooled using the inverse-variance weighting approach. A random-effects model was applied to estimate the summary effect., Results: A total of 14 131 potential articles were identified; there were eight studies eligible for qualitative and three for quantitative analysis. Three of four studies demonstrated transfer of surgical skills from robotic VR simulators to the operating room measured by time and technical surgical performance. Two of three studies found significant positive correlations between robotic VR simulator performance and intraoperative technical surgical performance; quantitative analysis revealed a positive combined correlation (r = 0.67, 95 per cent c.i. 0.22 to 0.88)., Conclusion: Technical surgical skills acquired through robotic VR simulator training can be transferred to the operating room, and operating room performance seems to be predictable by robotic VR simulator performance. VR training can therefore be justified before operating on patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Surgical resection is crucial for curative treatment of rectal cancer. Through multidisciplinary treatment, including radiochemotherapy and total mesorectal excision, survival has improved substantially. Consequently, more patients have to deal with side effects of treatment. The most recently introduced surgical technique is robotic-assisted surgery (RAS) which seems equally effective in terms of oncological control compared to laparoscopy. However, RAS enables further advantages which maximize the precision of surgery, thus providing better functional outcomes such as sexual function or contience without compromising oncological results. This review was done according to the PRISMA and AMSTAR-II guidelines and registered with PROSPERO (CRD42018104519). The search was planned with PICO criteria and conducted on Medline, Web of Science and CENTRAL. All screening steps were performed by two independent reviewers. Inclusion criteria were original, comparative studies for laparoscopy vs. RAS for rectal cancer and reporting of functional outcomes. Quality was assessed with the Newcastle-Ottawa scale. The search retrieved 9703 hits, of which 51 studies with 24,319 patients were included. There was a lower rate of urinary retention (non-RCTs: Odds ratio (OR) [95% Confidence Interval (CI)] 0.65 [0.46, 0.92]; RCTs: OR[CI] 1.29[0.08, 21.47]), ileus (non-RCTs: OR[CI] 0.86[0.75, 0.98]; RCTs: OR[CI] 0.80[0.33, 1.93]), less urinary symptoms (non-RCTs mean difference (MD) [CI] - 0.60 [- 1.17, - 0.03]; RCTs: - 1.37 [- 4.18, 1.44]), and higher quality of life for RAS (only non-RCTs: MD[CI]: 2.99 [2.02, 3.95]). No significant differences were found for sexual function (non-RCTs: standardized MD[CI]: 0.46[- 0.13, 1.04]; RCTs: SMD[CI]: 0.09[- 0.14, 0.31]). The current meta-analysis suggests potential benefits for RAS over laparoscopy in terms of functional outcomes after rectal cancer resection. The current evidence is limited due to non-randomized controlled trials and reporting of functional outcomes as secondary endpoints.

There is evidence that movement-based microbreaks can improve the cardiovascular health of desk-based employees, but their effect on mood states is yet to be investigated. As daily work tasks can potentially result in the loss of physical and psychological resources, the objective of this study was to measure the effect of movement microbreaks during formal work time on mood states. In a randomized-controlled pilot study with repeated measures (baseline, post-test, washout) of self-reported job stress and mood states (fatigue and vigor), police officers ( N = 43) were exposed to movement microbreaks during work hours. A multivariate significant difference between groups was noted after the intervention period. Further analysis revealed that the experimental group reported a latent reduction in job-related stress after the 3-months washout period. Although the study was conducted with a small sample, our preliminary findings suggest that interrupting sedentary work with movement microbreaks may have beneficial effects on employee mental health. The implications of movement microbreaks for mitigating work-related stress of first responders, including police, is discussed, along with directives for future research., (Copyright © 2020 Mainsbridge, Cooley, Dawkins, de Salas, Tong, Schmidt and Pedersen.)

Objective: To compare outcomes of endoscopic and surgical treatment for infected necrotizing pancreatitis (INP) based on results of randomized controlled trials (RCT)., Background: Treatment of INP has changed in the last two decades with adoption of interventional, endoscopic and minimally invasive surgical procedures for drainage and necrosectomy. However, this relies mostly on observational studies., Methods: We performed a systematic review following Cochrane and PRISMA guidelines and AMSTAR-2 criteria and searched CENTRAL, Medline and Web of Science. Randomized controlled trails that compared an endoscopic treatment to a surgical treatment for patients with infected walled-off necrosis and included one of the main outcomes were eligible for inclusion. The main outcomes were mortality and new onset multiple organ failure. Prospero registration ID: CRD42019126033 RESULTS: Three RCTs with 190 patients were included. Intention to treat analysis showed no difference in mortality. However, patients in the endoscopic group had statistically significant lower odds of experiencing new onset multiple organ failure (odds ratio (OR) confidence interval [CI] 0.31 [0.10, 0.98]) and were statistically less likely to suffer from perforations of visceral organs or enterocutaneous fistulae (OR [CI] 0.31 [0.10, 0.93]), and pancreatic fistulae (OR [CI] 0.09 [0.03, 0.28]). Patients with endoscopic treatment had a statistically significant lower mean hospital stay (Mean difference [CI] - 7.86 days [- 14.49, - 1.22]). No differences in bleeding requiring intervention, incisional hernia, exocrine or endocrine insufficiency or ICU stay were apparent. Overall certainty of evidence was moderate., Conclusion: There seem to be possible benefits of endoscopic treatment procedure. Given the heterogenous procedures in the surgical group as well as the low amount of randomized evidence, further studies are needed to evaluate the combination of different approaches and appropriate timepoints for interventions.

A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized.

Ventilation of carbon stored in the deep ocean is thought to play an important role in atmospheric CO 2 increases associated with Pleistocene deglaciations. The presence of this respired carbon has been recorded by an array of paleoceanographic proxies from various locations across the global ocean. Here we present a new sediment core from the Eastern Equatorial Pacific (EEP) Ocean spanning the last 180,000 years and reconstruct high-resolution 230 Th-derived fluxes of 232 Th and excess barium, along with redox-sensitive uranium concentrations to examine past variations in dust delivery, export productivity, and bottom-water oxygenation, respectively. Our bottom-water oxygenation record is compared to other similar high-resolution records from across the Pacific and in the Southern Ocean. We suggest that the deep Pacific is a site of respired carbon storage associated with periods of decreased global atmospheric CO 2 concentration during the LGM, confirming the conclusions from a wealth of previous studies. However, our study is the first to show a similar relationship beyond the last glacial, extending to at least 70,000 years.

Background: The most commonly performed bariatric procedures are laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (LSG). Impact of learning curves on operative outcome has been well shown, but the necessary learning curves have not been clearly defined. This study provides a systematic review of the literature and proposes a standardization of phases of learning curves for RYGB and LSG., Methods: A systematic literature search was performed using PubMed, Web of Science, and CENTRAL databases. All studies specifying a number or range of approaches to characterize the learning curve for RYGB and LSG were selected., Results: A total of 28 publications related to learning curves for 27,770 performed bariatric surgeries were included. Parameters used to determine the learning curve were operative time, complications, conversions, length of stay, and blood loss. Learning curve range was 30-500 (RYGB) and 30-200 operations (LSG) according to different definitions and respective phases of learning curves. Learning phases described the number of procedures necessary to achieve predefined skill levels, such as competency, proficiency, and mastery., Conclusions: Definitions of learning curves for bariatric surgery are heterogeneous. Introduction of the three skill phases competency, proficiency, and mastery is proposed to provide a standardized definition using multiple outcome variables to enable better comparison in the future. These levels are reached after 30-70, 70-150, and up to 500 RYGB, and after 30-50, 60-100, and 100-200 LSG. Training curricula, previous laparoscopic experience, and high procedure volume are hallmarks for successful outcomes during the learning curve.

Background: Laparoscopic suturing and knot tying is essential for advanced laparoscopic procedures and requires training outside of the operating room. However, personal instruction by experienced surgeons is limitedly available. To address this, the concept of combining e-learning with practical training has become of interest. This study aims to investigate the influence of the first-person perspective in instructional videos, as well as the feasibility of a completely self-directed training curriculum for laparoscopic suturing and knot tying., Materials and Methods: Ninety-one laparoscopically naïve medical students were randomised into two groups training with e-learning videos in either the first-person perspective (combining endoscopic view and view of hands/instruments/forearm motion) or the endoscopic view only. Both groups trained laparoscopic suturing and knot tying in teams of two until reaching predefined proficiency levels. Blinded, trained raters regularly assessed the participants' performance by using validated checklists. After training, participants filled out questionnaires regarding training experience and personal characteristics., Results: Average training time to reach proficiency did not differ between groups [first-person perspective (min): 112 ± 44; endoscopic view only (min): 109 ± 47; p = 0.746]. However, participants from both groups perceived the first-person perspective as useful for learning new laparoscopic skills. Both groups showed similar baseline performances and improved significantly after training [Objective Structured Assessment of Technical Skills (OSATS) (max. 37 points): first-person perspective: 30.3 ± 2.3; endoscopic view only: 30.8 ± 2.3]. All participants managed to reach proficiency, needing 8-43 attempts without differences between groups. Visuospatial abilities (mental rotation) seemed to enhance the learning curve., Conclusion: Modifying instructional videos to the first-person perspective did not translate into a better performance in this setting but was welcomed by participants. Completely self-directed training with the use of e-learning can be a feasible training approach to achieve technical proficiency in laparoscopic suturing and knot tying in a training setting.

Introduction: The most common way of assessing surgical performance is by expert raters to view a surgical task and rate a trainee's performance. However, there is huge potential for automated skill assessment and workflow analysis using modern technology. The aim of the present study was to evaluate machine learning (ML) algorithms using the data of a Myo armband as a sensor device for skills level assessment and phase detection in laparoscopic training., Materials and Methods: Participants of three experience levels in laparoscopy performed a suturing and knot tying task on silicon models. Experts rated performance using Objective Structured Assessment of Surgical Skills (OSATS). Participants wore Myo armbands (Thalmic Labs™, Ontario, Canada) to record acceleration, angular velocity, orientation, and Euler orientation. ML algorithms (decision forest, neural networks, boosted decision tree) were compared for skill level assessment and phase detection., Results: 28 participants (8 beginner, 10 intermediate, 10 expert) were included, and 99 knots were available for analysis. A neural network regression model had the lowest mean absolute error in predicting OSATS score (3.7 ± 0.6 points, r 2 = 0.03 ± 0.81; OSATS min.-max.: 4-37 points). An ensemble of binary-class neural networks yielded the highest accuracy in predicting skill level (beginners: 82.2% correctly identified, intermediate: 3.0%, experts: 79.5%) whereas standard statistical analysis failed to discriminate between skill levels. Phase detection on raw data showed the best results with a multi-class decision jungle (average 16% correctly identified), but improved to 43% average accuracy with two-class boosted decision trees after Dynamic time warping (DTW) application., Conclusion: Modern machine learning algorithms aid in interpreting complex surgical motion data, even when standard analysis fails. Dynamic time warping offers the potential to process and compare surgical motion data in order to allow automated surgical workflow detection. However, further research is needed to interpret and standardize available data and improve sensor accuracy.

Introduction: Virtual reality (VR-)trainers are well integrated in laparoscopic surgical training. However, objective feedback is often provided in the form of single parameters, e.g., time or number of movements, making comparisons and evaluation of trainees' overall performance difficult. Therefore, a new standard for reporting outcome data is highly needed. The aim of this study was to create a weighted, expert-based composite score, to offer simple and direct evaluation of laparoscopic performance on common VR-trainers., Materials and Methods: An integrated analytic hierarchy process-Delphi survey was conducted with 14 international experts to achieve a consensus on the importance of different skill categories and parameters in evaluation of laparoscopic performance. A scoring algorithm was established to allow comparability between tasks and VR-trainers. A weighted composite score was calculated for basic skills tasks and peg transfer on the LapMentor™ II and III and validated for both VR-trainers., Results: Five major skill categories (time, efficiency, safety, dexterity, and outcome) were identified and weighted in two Delphi rounds. Safety, with a weight of 67%, was determined the most important category, followed by efficiency with 17%. The LapMentor™-specific score was validated using 15 (14) novices and 9 experts; the score was able to differentiate between both groups for basic skills tasks and peg transfer (LapMentor™ II: Exp: 86.5 ± 12.7, Nov. 52.8 ± 18.3; p < 0.001; LapMentor™ III: Exp: 80.8 ± 7.1, Nov: 50.6 ± 16.9; p < 0.001)., Conclusion: An effective and simple performance measurement was established to propose a new standard in analyzing and reporting VR outcome data-the Heidelberg virtual reality (VR) score. The scoring algorithm and the consensus results on the importance of different skill aspects in laparoscopic surgery are universally applicable and can be transferred to any simulator or task. By incorporating specific expert baseline data for the respective task, comparability between tasks, studies, and simulators can be achieved.

The role of the 4f orbitals in bonding is examined for the molecules cerium monoxide and cerium dioxide that have cerium formally in the +2 and +4 oxidation states, respectively. It is shown that the 4f orbitals are used primarily for polarization of the 5d orbitals when cerium is in the lower oxidation state, while the 4f orbitals play a significant role in chemical bonding via 5d/4f hybridization when cerium is in the +4 oxidation state.

Full-valence relativistic accurate atomic minimal basis set (AAMBS) orbitals are developed for the sixth-row elements from cesium to radon, including the lanthanides. Saturated primitive atomic basis sets are developed and subsequently used to form the AAMBS orbitals. By virtue of the use of a saturated basis, properties computed based on the AAMBS orbitals are basis set independent. In molecules, the AAMBS orbitals can be used to construct valence virtual orbitals (VVOs) that provide chemically meaningful ab initio lowest unoccupied molecular orbitals (LUMOs) with basis set independent orbital energies. The optimized occupied molecular orbitals complemented with the VVOs form a set of full-valence molecular orbitals. They can be transformed into a set of oriented quasi-atomic orbitals (QUAOs) that provide information on intramolecular bonding via an intrinsic density analysis. In the present work, the development of the AAMBS for the sixth row is presented.

The ground and low-lying excited states of four alternating Si/C annulenes, H n Si n/2 C n/2 with n = 4, 6, 8, and 10, have been investigated by ab initio molecular orbital methods and compared to those of their all-carbon and all-silicon analogues. In the ground state, all of the Si/C-mixed annulenes, except for the largest 10-membered annulene (H 10 Si 5 C 5 ), assume equal-bond-length structures by adopting a closed-shell electronic structure in the possible highest symmetry. For the largest H 10 Si 5 C 5 , the trend of the bond delocalization still remains but the circular structure is considerably distorted and nonplanar due to severe angle strain. In the low-lying singlet (S 1 ) and triplet (T 1 ) states, the geometry of the compounds tends to be nonplanar as the excitations produce silyl radical character. Relative energies of the T 1 and S 1 states of the 6-membered ring, compared to those of the respective ground states (S 0 ), are higher than those of the 4- and 8-membered rings, suggesting a special stability for H 6 Si 3 C 3 . The planar rhombus shape of the formally antiaromatic H 4 Si 2 C 2 suggests that a synthetic effort is merited. Bonding analyses are given to support the conclusions reached on the basis of geometric structures and excited-state energetics.