Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

The synergistic role of virtual coaching with simulation-based mastery learning for upper endoscopy.

Introduction: Our simulation-based mastery learning (SBML) curriculum, delivered in person, has been shown to successfully train novices in structured esophagogastroduodenoscopy (EGD). SBML with virtual coaching (VC) has the potential to improve the effectiveness and efficiency of endoscopy training and expand access to trainees from around the world. We share our observations conducting an EGD training course using SBML with VC. Methods: We conducted a 1-week virtual SBML course for novice trainees across seven academic centers in the USA and Asia. The cognitive component was delivered using an online learning platform. For technical skills, a virtual coach supervised hands-on training and local coaches provided assistance when needed. At the end of training, an independent rater assessed simulation-based performance using a validated assessment tool. We assessed the clinical performance of 30 EGDs using the ASGE Assessment of Competency in Endoscopy tool. We compared the trainees' scores to our cohort trained using in-person SBML training using non-inferiority t-tests. Results: We enrolled 21 novice trainees (mean age: 30.8 ± 3.6 years; female: 52%). For tip deflection, the trainees reached the minimum passing standard after 31 ± 29 runs and mastery after 52 ± 37 runs. For structured EGD, the average score for the overall exam was 4.6 ± 0.6, similar to the in-person cohort (4.7 ± 0.5, p = 0.49). The knowledge-based assessment was also comparable (virtual coaching: 81.9 ± 0.1; direct coaching: 78.3 ± 0.1; p = 0.385). Over time, our novice trainees reached clinical competence at a similar rate to our historical in-person control. Conclusions: VC appears feasible and effective for training novice gastroenterology trainees. VC allowed us to scale our SBML course, expand access to experts, and administer SBML simultaneously across different sites at the highest standards.

Varied Trainee Competence in Cold Snare Polypectomy: Results of the COMPLETE Randomized Controlled Trial.

INTRODUCTION: Cold snare polypectomy (CSP) is strongly recommended as the optimal technique for the complete removal of small polyps. Though significant variability in polypectomy technique and quality has been established, the learning curve and impact of targeted training on CSP are unknown. Video feedback has shown promise as an effective pedagogy to improve performance among surgical trainees. We aimed to compare CSP performance between trainees who received video-based feedback and those who received conventional apprentice-based concurrent feedback. We hypothesized that video-based feedback would accelerate competence. METHODS: We conducted a single-blinded, randomized controlled trial on competence for CSP of polyps <1 cm, comparing video-based feedback with conventional feedback. We randomly assigned deidentified consecutively recorded CSP videos to blinded raters to assess using the CSP Assessment Tool. We shared cumulative sum learning curves every 25 CSP with each trainee. The video feedback trainees also received biweekly individualized terminal feedback. Control trainees received conventional feedback during colonoscopy. The primary outcome was CSP competence. We also assessed competence across domains and change over polypectomy volume. RESULTS: We enrolled and randomized 22 trainees, 12 to video-based feedback and 10 to conventional feedback, and evaluated 2,339 CSP. The learning curve was long; 2 trainees (16.7%) in the video feedback achieved competence, after a mean of 135 polyps, and no one in the control ( P = 0.481) achieved competence. Overall and in all steps of CSP, a higher percentage of the video feedback group met competence, increasing 3% every 20 CSP ( P = 0.0004). DISCUSSION: Video feedback aided trainees to competence in CSP. However, the learning curve was long. Our findings strongly suggest that current training methods are not sufficient to support trainees to competency by the completion of their fellowship programs. The impact of new training methods, such as simulation-based mastery learning, should be assessed to determine whether such methods can result in achievement of competence at a faster rate; ClinicalTrials.gov : NCT03115008.

Managing First-Line Metastatic Renal Cell Carcinoma: Favorable-Risk Disease.

Defining metastatic renal-cell carcinoma as a favorable risk depends on clinical risk-stratification tools such as the International Metastatic Renal Cell Carcinoma Database Consortium or the Memorial Sloan-Kettering Cancer Center scores. The favorable-risk disease tends to have better prognosis and survival compared with disease stratified as either intermediate or poor risk and can be attributed in part to an indolent tumor biology. Several phase 3 clinical trials have demonstrated an improvement in progression-free survival and objective response rate, but not overall survival benefit with combinations of immunotherapy and vascular endothelial growth factor tyrosine kinase inhibitors compared with sunitinib in favorable-risk disease.

Longitudinal outcomes of the endoscopic resection of nonpolypoid dysplastic lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia. According to the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations, "After complete removal of endoscopically resectable nonpolypoid dysplastic lesions, surveillance colonoscopy is suggested rather than colectomy." We sought to add data to the literature and hypothesized that the endoscopic resection of nonpolypoid colorectal dysplasia (NP-CRD) is safe and effective. METHODS: We conducted a retrospective study of a large cohort of patients with IBD at 2 medical centers who underwent colonoscopy between 2007 and 2018. Patients with at least 1 nonpolypoid lesion ≥10 mm were identified. We measured the feasibility of endoscopic resection, incidence of local recurrence, incidence of cancer, need for surgery, and frequency of adverse events. RESULTS: We studied 326 patients who underwent a mean ± standard deviation of 3.6 ± 3.0 (range, 1-16) colonoscopies during a total follow-up of 1208 patient-years. In 36 patients, 161 lesions ≥10 mm were identified, 63 of which were nonpolypoid (mean size, 17.8 ± 8.9 mm; range, 10-45 mm) (prevalence, 7.7%). The majority of nonpolypoid lesions (96.8% [61 of 63]) were managed endoscopically. Four lesions (mean index lesion size, 32.5 ±11.0 mm) had small local recurrences that were successfully retreated with endoscopy. There were no severe adverse events related to IBD or colorectal cancer observed in the follow-up period. CONCLUSIONS: In this IBD cohort, surveillance colonoscopy rather than colectomy was found to be safe and effective in patients with NP-CRD after undergoing endoscopic resection. After complete removal of endoscopically resectable NP-CRD, surveillance colonoscopy should be considered a safe and effective first-line strategy rather than colectomy.

Adding efficiency to proficiency: a study of trainee polypectomy efficiency metrics.

BACKGROUND: Although validated colonoscopy assessment tools exist, they do not measure efficiency. This study aimed to assess content validity of polypectomy efficiency (PE) and neoplastic polypectomy efficiency (NPE) as colonoscopy efficiency indices. METHODS: Data from a randomized controlled trial evaluating polypectomy among gastroenterology trainees were utilized. PE and NPE were defined as number of polyps (or neoplastic polyps) removed/withdrawal time × 100. Content validity was assessed by determining the association between efficiency indices and polypectomy times. RESULTS: 20 trainees performed 601 colonoscopies. There was a strong association between PE/NPE and actual polypectomy times: as polypectomy time increased by 1 minute, the PE decreased by 0.48 (P = 0.001) and NPE decreased by 0.24 (P = 0.03). CONCLUSIONS: The study proposed and provided content validity for PE and NPE as colonoscopy efficiency indices.

Use of the Endoscopic Clipping Over the Scope Technique to Treat Acute Severe Lower Gastrointestinal Bleeding in the Colon and Anal Transition Zone.

Endoscopic treatment of lower gastrointestinal bleeding can be challenging. This article reports on the use of the endoscopic clipping over the scope technique to treat acute severe lower gastrointestinal bleeding. In particular, it describes the approaches and outcomes of using the technique for acute severe bleeding in the colon and the anal transition zone. The following synopsis is the one that you supplied, but lightly copyedited. Please confirm OK. Please note that the synopsis will appear in PubMed: Endoscopic treatment of lower gastrointestinal bleeding can be challenging. This article reports on the use of the endoscopic clipping over the scope technique to treat acute severe lower gastrointestinal bleeding. In particular, it describes the approaches and outcomes of using the technique for acute severe bleeding in the colon and the anal transition zone.

Endoscopic Assessment of the Malignant Potential of the Nonpolypoid (Flat and Depressed) Colorectal Neoplasms: Thinking Fast, and Slow.

Current endoscopy training methodology does not meet the learning traits, skills, and needs of the newer generation of gastroenterologists. This article provides information on assessment of the malignant potential of colorectal neoplasms. It takes a modern approach on the topic and integrates relevant information that aligns with the thinking process. The theory of thinking fast (reflex) and slow (rational) is used. By doing so, it is hoped that the learning process can be expedited and practiced immediately. The focus is on preresection assessment of nonpolypoid colorectal neoplasms. Assessment of polypoid, sessile-serrated adenoma/polyp, or inflammatory bowel disease dysplasia is briefly discussed.

Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation.

Arthropod-borne flaviviruses cause life-threatening diseases associated with endothelial hyperpermeability and vascular leak. We recently found that vascular leak can be triggered by dengue virus (DENV) non-structural protein 1 (NS1) via the disruption of the endothelial glycocalyx-like layer (EGL). However, the molecular determinants of NS1 required to trigger EGL disruption and the cellular pathway(s) involved remain unknown. Here we report that mutation of a single glycosylated residue of NS1 (N207Q) abolishes the ability of NS1 to trigger EGL disruption and induce endothelial hyperpermeability. Intriguingly, while this mutant bound to the surface of endothelial cells comparably to wild-type NS1, it was no longer internalized, suggesting that NS1 binding and internalization are distinct steps. Using endocytic pathway inhibitors and gene-specific siRNAs, we determined that NS1 was endocytosed into endothelial cells in a dynamin- and clathrin-dependent manner, which was required to trigger endothelial dysfunction in vitro and vascular leak in vivo. Finally, we found that the N207 glycosylation site is highly conserved among flaviviruses and is also essential for West Nile and Zika virus NS1 to trigger endothelial hyperpermeability via clathrin-mediated endocytosis. These data provide critical mechanistic insight into flavivirus NS1-induced pathogenesis, presenting novel therapeutic and vaccine targets for flaviviral diseases.