Does rating the operation videos with a checklist score improve the effect of E-learning for bariatric surgical training? Study protocol for a randomized controlled trial

Background: Laparoscopic training has become an important part of surgical education. Laparoscopic Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure performed. Surgeons must be well trained prior to operating on a patient. Multimodality training is vital for bariatric surgery. E-learning with videos is a standard approach for training. The present study investigates whether scoring the operation videos with performance checklists improves learning effects and transfer to a simulated operation. Methods/design: This is a monocentric, two-arm, randomized controlled trial. The trainees are medical students from the University of Heidelberg in their clinical years with no prior laparoscopic experience. After a laparoscopic basic virtual reality (VR) training, 80 students are randomized into one of two arms in a 1:1 ratio to the checklist group (group A) and control group without a checklist (group B). After all students are given an introduction of the training center, VR trainer and laparoscopic instruments, they start with E-learning while watching explanations and videos of RYGB. Only group A will perform ratings with a modified Bariatric Objective Structured Assessment of Technical Skill (BOSATS) scale checklist for all videos watched. Group B watches the same videos without rating. Both groups will then perform an RYGB in the VR trainer as a primary endpoint and small bowel suturing as an additional test in the box trainer for evaluation. Discussion: This study aims to assess if E-learning and rating bariatric surgical videos with a modified BOSATS checklist will improve the learning curve for medical students in an RYGB VR performance. This study may help in future laparoscopic and bariatric training courses. Trial registration: German Clinical Trials Register, DRKS00010493. Registered on 20 May 2016

Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis

IntroductionVulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer.Materials and methodsFollowing a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I2 and the Cochrane Q χ2 statistics.ResultsOut of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses.Discussion and conclusionThis study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD4202339188

Predictors of Psychological Distress in Women with Endometriosis during the COVID-19 Pandemic

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

DataSheet_1_Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis.docx

IntroductionVulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer.Materials and methodsFollowing a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I2 and the Cochrane Q χ2 statistics.ResultsOut of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses.Discussion and conclusionThis study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023391888</p

Estrogen controls the survival of BRCA1-deficient cells via a PI3K–NRF2-regulated pathway

Our establishment of a connection between the phosphatidylinositol 3-kinase (PI3K) and NRF2 pathways provides the basis for the tissue specificity of BRCA1-related cancers. Because BRCA1 is a vital component of the intracellular machinery maintaining genomic stability, BRCA1 functions as a major tumor suppressor in cells of all types. However, BRCA1-related cancers occur overwhelmingly in breasts and ovaries. Our work demonstrates that estrogen (E2) acts via the PI3K–AKT pathway to regulate NRF2 activation in BRCA1-deficient cells, resulting in the induction of antioxidant genes that protect the cell from reactive oxygen species-induced death. BRCA1-deficient cells are thus allowed to survive and may accumulate mutations, such as loss of PTEN, that perpetuate NRF2 activation. Our work supports the emerging clinical strategy of treating BRCA1-related cancers with PI3K inhibitors. Mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. The mechanism underlying the tissue-specific nature of BRCA1’s tumor suppression is obscure. We previously showed that the antioxidant pathway regulated by the transcription factor NRF2 is defective in BRCA1-deficient cells. Reactivation of NRF2 through silencing of its negative regulator KEAP1 permitted the survival of BRCA1-null cells. Here we show that estrogen (E2) increases the expression of NRF2-dependent antioxidant genes in various E2-responsive cell types. Like NRF2 accumulation triggered by oxidative stress, E2-induced NRF2 accumulation depends on phosphatidylinositol 3-kinase–AKT activation. Pretreatment of mammary epithelial cells (MECs) with the phosphatidylinositol 3-kinase inhibitor BKM120 abolishes the capacity of E2 to increase NRF2 protein and transcriptional activity. In vivo the survival defect of BRCA1-deficient MECs is rescued by the rise in E2 levels associated with pregnancy. Furthermore, exogenous E2 administration stimulates the growth of BRCA1-deficient mammary tumors in the fat pads of male mice. Our work elucidates the basis of the tissue specificity of BRCA1-related tumor predisposition, and explains why oophorectomy significantly reduces breast cancer risk and recurrence in women carrying BRCA1 mutations

Table_1_Effects of intermittent fasting on quality of life tolerance of chemotherapy in patients with gynecological cancers: study protocol of a randomized-controlled multi-center trial.docx

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 Registrationhttps://drks.de, identifier DRKS00031429.</p

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used