Magnetically Assisted Capsule Endoscopy: A Viable Alternative to Conventional Flexible Endoscopy of the Stomach?

INTRODUCTION: Oesophagogastroduodenoscopy is the investigation of choice to identify mucosal lesions of the upper gastrointestinal tract, but it is poorly tolerated by patients. A simple non-invasive technique to image the upper gastrointestinal tract, which could be made widely available, would be beneficial to patients. Capsule endoscopy is well tolerated by patients but the stomach has proved difficult to visualise accurately with capsule technology due to its’ capacious nature and mucosal folds, which can obscure pathology. MiroCam Navi (Intromedic Ltd, Seoul, Korea) is a capsule endoscope containing a small amount of magnetic material which has been made available with a handheld magnet which might allow a degree of control. This body of work aims to address whether this new technology could be a feasible alternative to conventional flexible endoscopy of the stomach. METHODS: Four studies were conducted to test this research question. The first explores the feasibility of magnetically assisted capsule endoscopy of the stomach and operator learning curve in an ex vivo porcine model. This was followed by a randomised, blinded trial comparing magnetically assisted capsule endoscopy to conventional flexible endoscopy in ex vivo porcine stomach models. Subsequently a prospective, single centre randomised controlled trial in humans examined whether magnetically assisted capsule endoscopy could enhance conventional small bowel capsule endoscopy by reducing gastric transit time. Finally a blinded comparison of diagnostic yield of magnetically assisted capsule endoscopy compared to oesophagogastroduodenoscopy was performed in patients with recurrent or refractory iron deficiency anaemia. RESULTS: In the first study all stomach tags were identified in 87.2% of examinations and a learning curve was demonstrated (mean examination times for the first 23 and second 23 procedures 10.28 and 6.26 minutes respectively (p<0.001). In the second study the difference in sensitivities between oesophagogastroduodenoscopy and conventional flexible endoscopy for detecting beads within an ex vivo porcine stomach model was 1.11 (95% CI 0.06, 28.26) proving magnetically assisted capsule endoscopy to be non-inferior to flexible endoscopy. In the first human study, although there was no significant difference in gastric transit time or capsule endoscopy completion rate between the two groups (p=0.12 and p=0.39 respectively), the time to first pyloric image was significantly shorter in the intervention group (p=0.03) suggesting that magnetic control hastens capsular transit to the gastric antrum but cannot impact upon duodenal passage. In the last study, a total of 38 pathological findings were identified in this comparative study of magnetically assisted capsule endoscopy and conventional endoscopy. Of these, 16 were detected at both procedures, while flexible endoscopy identified 14 additional lesions not seen at magnetically assisted capsule endoscopy and magnetically assisted capsule endoscopy detected 8 abnormalities not seen by oesophagogastroduodenoscopy. No adverse events occurred in either of the human trials. Finally magnetically steerable capsule endoscopy induced less procedural pain, discomfort and distress than oesophagogastroduodenoscopy (p=0.0009, p=0.001 and p=0.006 respectively). CONCLUSION: Magnetically assisted capsule endoscopy is safe, well tolerated and a viable alternative to conventional endoscopy. Further research to develop and improve this new procedure is recommended

Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care

BACKGROUND: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited. AIMS: To assess the yield of IBD from FC testing in primary care. METHODS: Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed. RESULTS: 410 patients (162 male; median age 42; range 16-91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17-91)) were FC+ (median FC 116.5 µg/g (51-1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC-) patients (FC ≤50 µg/g) (median age 47 (19-76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn's disease, 4 microscopic colitis). 8/11 were FC+ (range 67-1170) and 3 FC-. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%. CONCLUSIONS: FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly

Simulated Basic Skills Training: Graduate Nursing Students Teaching Medical Students: A Work in Progress

For a number of years, Advanced Practice Nursing (APN) students have taught interested 1st year medical students to perform intramuscular injections prior to their participation in community flu clinics. When several 4th year medical students needed documentation of competency in intravenous (IV) cannulation prior to participating in an elective rotation at another institution, the Medical School\u27s Dean of Students called the Director of Interdisciplinary Partnerships in the Graduate School of Nursing to request assistance. In fact, all medical students need IV therapy training prior to graduation, not just those who seek out visiting clerkships at other medical schools. Integration of IV training into the Undergraduate Medical Education Surgery Clerkship Curriculum supports the clinical objectives of the Surgery Clerkship along with the developing use of simulation within in the medical school. This need led to the development of this interdisciplinary simulation education initiative. Presented at the 2008 Society on Simulation in Healthcare Conference

Framework for a Community Health Observing System for the Gulf of Mexico Region: Preparing for Future Disasters

© Copyright © 2020 Sandifer, Knapp, Lichtveld, Manley, Abramson, Caffey, Cochran, Collier, Ebi, Engel, Farrington, Finucane, Hale, Halpern, Harville, Hart, Hswen, Kirkpatrick, McEwen, Morris, Orbach, Palinkas, Partyka, Porter, Prather, Rowles, Scott, Seeman, Solo-Gabriele, Svendsen, Tincher, Trtanj, Walker, Yehuda, Yip, Yoskowitz and Singer. The Gulf of Mexico (GoM) region is prone to disasters, including recurrent oil spills, hurricanes, floods, industrial accidents, harmful algal blooms, and the current COVID-19 pandemic. The GoM and other regions of the U.S. lack sufficient baseline health information to identify, attribute, mitigate, and facilitate prevention of major health effects of disasters. Developing capacity to assess adverse human health consequences of future disasters requires establishment of a comprehensive, sustained community health observing system, similar to the extensive and well-established environmental observing systems. We propose a system that combines six levels of health data domains, beginning with three existing, national surveys and studies plus three new nested, longitudinal cohort studies. The latter are the unique and most important parts of the system and are focused on the coastal regions of the five GoM States. A statistically representative sample of participants is proposed for the new cohort studies, stratified to ensure proportional inclusion of urban and rural populations and with additional recruitment as necessary to enroll participants from particularly vulnerable or under-represented groups. Secondary data sources such as syndromic surveillance systems, electronic health records, national community surveys, environmental exposure databases, social media, and remote sensing will inform and augment the collection of primary data. Primary data sources will include participant-provided information via questionnaires, clinical measures of mental and physical health, acquisition of biological specimens, and wearable health monitoring devices. A suite of biomarkers may be derived from biological specimens for use in health assessments, including calculation of allostatic load, a measure of cumulative stress. The framework also addresses data management and sharing, participant retention, and system governance. The observing system is designed to continue indefinitely to ensure that essential pre-, during-, and post-disaster health data are collected and maintained. It could also provide a model/vehicle for effective health observation related to infectious disease pandemics such as COVID-19. To our knowledge, there is no comprehensive, disaster-focused health observing system such as the one proposed here currently in existence or planned elsewhere. Significant strengths of the GoM Community Health Observing System (CHOS) are its longitudinal cohorts and ability to adapt rapidly as needs arise and new technologies develop

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies