Size-Exclusion Chromatography as a Technique for the Investigation of Novel Extracellular Vesicles in Cancer.

Cancer cells release extracellular vesicles, which are a rich target for biomarker discovery and provide a promising mechanism for liquid biopsy. Size-exclusion chromatography (SEC) is an increasingly popular technique, which has been rediscovered for the purposes of extracellular vesicle (EV) isolation and purification from diverse biofluids. A systematic review was undertaken to identify all papers that described size exclusion as their primary EV isolation method in cancer research. In all, 37 papers were identified and discussed, which showcases the breadth of applications in which EVs can be utilised, from proteomics, to RNA, and through to functionality. A range of different methods are highlighted, with Sepharose-based techniques predominating. EVs isolated using SEC are able to identify cancer cells, highlight active pathways in tumourigenesis, clinically distinguish cohorts, and remain functionally active for further experiments.

The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers.

Pancreatic Ductal Adenocarcinoma (PDAC) and biliary-tract cancers (BTC) often present at a late stage, and consequently patients have poor survival-outcomes. Circular RNAs (circRNAs) are non-coding RNA molecules whose role in tumourigenesis has recently been realised. They are stable, conserved and abundant, with tissue-specific expression profiles. Therefore, significant interest has arisen in their use as potential biomarkers for PDAC and BTC. High-throughput methods and more advanced bioinformatic techniques have enabled better profiling and progressed our understanding of how circRNAs may function in the competing endogenous RNA (ceRNA) network to influence the transcriptome in these cancers. Therefore, the aim of this systematic review was to describe the roles of circRNAs in PDAC and BTC, their potential as biomarkers, and their function in the wider ceRNA network in regulating microRNAs and the transcriptome. Medline, Embase, Scopus and PubMed were systematically reviewed to identify all the studies addressing circRNAs in PDAC and BTC. A total of 32 articles were included: 22 considering PDAC, 7 for Cholangiocarcinoma (CCA) and 3 for Gallbladder Cancer (GBC). There were no studies investigating Ampullary Cancer. Dysregulated circRNA expression was associated with features of malignancy in vitro, in vivo, and ex vivo. Overall, there have been very few PDAC and BTC tissues profiled for circRNA signatures. Therefore, whilst the current studies have demonstrated some of their functions in these cancers, further work is required to elucidate their potential role as cancer biomarkers in tissue, biofluids and biopsies.

Analysis of the first 2645 registrations at the research registry®: A global repository for all study types involving human participants.

BACKGROUND: The Declaration of Helsinki has called for the registration of all research studies involving human participants. Despite this, prior registries did not allow registration certain study types, or retrospective registration. The Research Registry® (www.researchregistry.com) was established in 2015 to provide a venue of registration for any study involving human participants. METHODS: and analysis: This retrospective database analysis describes the first 3000 registrations received by the Research Registry®. Since the launch of the Registry in 2015, we have collected data on each registration and excluded inappropriate registrations through a weekly curation process. The characteristics of all studies registered is presented. Each registration was marked against a quality score by two researchers acting independently, and we describe how this has changed over time. No ethical approval was required for this data only study including no human participants. RESULTS: Of 3000 registrations, we included 2645 that were submitted to the registry between February 2015 and October 2017. The number of registrations increased year on year, and we now receive between 60 and 80 registrations per month. One fifth of registrations were from China (537 [20.3%]). Retrospective observational studies were most commonly registered (1125 [42.5%]), and studies included in excess of 20 million patients (median 80 [IQR:25-200]). The quality score of registrations improved over the time (Kruskal-Wallis p < 0.05), and the 'control/comparator' component of the quality score was most poorly completed (completed by 1199 [54%]). CONCLUSION: The Research Registry® has received registrations on over 2500 registrations, including in excess of 20 million patients, with the quality of registrations improving over time. Retrospective observational studies and case series are the most commonly registered.

The Academic Surgical Collaborative: A three-year review of a trainee research collaborative.

INTRODUCTION: The Academic Surgical Collaborative (ASC) is a trainee research collaborative (TRC) formed in the UK in October 2014. Three years on, the achievements are presented along with advice for emerging and established TRCs. Methods: A retrospective review of internal, member-maintained ASC records was conducted. Membership numbers, PubMed indexed publications, presentations and prizes awarded were all calculated over time. Google Scholar was used to calculate citations per ASC publication. An online survey was distributed to members to ascertain member satisfaction. RESULTS: With 62 active members (predominantly medical students) the ASC has published 33 PubMed indexed papers over three years, with a mean of 21 citations per paper (SD 89, range 0-491). 54 presentations have been delivered and eight prizes have been awarded for ASC research projects. 60% of ASC members believe the ASC delivers research that improves patient care. Key learning points for the ASC have been the use of a set of resources distributed to new members, the value of regular meetings, close mentoring throughout research projects to develop the skills of junior researchers, encouragement for junior members to present at conferences, and an ongoing focus on research conduct and improving evidence based medicine. CONCLUSIONS: The ASC has fulfilled many of its goals set out at its inception. The ASCs subsequent aims are to enhance existing research training for junior members, advances in the field of core outcome development and also multi-collaborative research.

Reflective practice in health care and how to reflect effectively.

Reflective practice is a paper requirement of your career progression in health care. However, if done properly, it can greatly improve your skills as a health care provider. This article provides some structure to reflective practice to allow a health care provider to engage more with reflective practice and get more out of the experience.

How to design and deliver a local teaching program.

Teaching is an invaluable aspect of any medical or surgical career. Many trainees will find themselves delivering teaching at several stages in their career and in this "How to" article we explain how to design, set up, and deliver a successful teaching program, as well as how to evidence this in your portfolio.

How to conduct a clinical audit and quality improvement project.

Audits and quality improvement projects are vital aspects of clinical governance and continual service improvement in medicine. In this article we describe the process of clinical audit and quality improvement project. Guidance is also provided on how to design an effective audit and bypass barriers encountered during the process.

The use of study registration and protocols in plastic surgery research: A systematic review.

BACKGROUND: In 2013, the Declaration of Helsinki changed to mandate that all research studies involving human subjects, rather than just clinical trials alone, must have a protocol registered in a publicly accessible database prior to the enrolment of the first patient. The objective of this work was to assess the number of research studies involving human participants published in leading journals of plastic surgery that had either published a protocol or registered a protocol with a publicly accessible database. MATERIALS AND METHODS: This systematic review examined all research articles involving human participants published in Plastic and Reconstructive Surgery, The Journal of Plastic Reconstructive and Aesthetic Surgery and The Annals of Plastic Surgery from 1st April 2014-31st March 2015. The primary outcome measure was whether each study had either published or registered a protocol with any mainstream registry database. ClinicalTrials.gov, the International Standard Randomized Control Trial Number (ISRCTN) registry, the WHO (World Health Organisation) International Clinical Trials Registry Platform, The Cochrane Collaboration, the Research Registry, PROSPERO and PubMed were all reviewed. RESULTS: Of 595 included articles, the most common study designs were case series (n = 185, 31.1%). There were 24 randomized controlled trials (RCTs, 4.0%). A total of 24 studies had a protocol registered (4.0%). The most common database to register a protocol was with ClinicalTrials.gov (n = 17). The study design that most commonly had a registered protocol was the RCT (n = 8 of 24, 33.3% of RCTs). Three studies published a protocol in a journal (0.6%). CONCLUSION: Publication or registration of protocols for recent studies involving human participants in major plastic surgery journals is low. There is considerable scope to improve this and guidance is provided.

Surveying opinions of 149 registrants to the Research Registry: Awareness of and attitudes towards research registration.

BACKGROUND: Research registration is an important ethical principle in the Declaration of Helsinki, however, progress to increase registration has been slow. Understanding the attitudes of users towards registries may provide insights into increase research registration. In this survey-based study, we sought to gain insight from users of a single global research registry, the Research Registry® (www.researchregistry.com). METHODS: A Google Forms survey was created and emailed to all users of the Research Registry® (n = 1432). Multiple choice and free-text answers were analyzed using descriptive statistics and thematic analysis respectively. RESULTS: From 925 contactable registrations, 149 (16.1%) completed the survey. The most commonly registered study type was retrospective cohort (32.2%). 23 registrations (15.4%) were made during the planning or conception of the study, whereas 67 (45.0%) registered at the time of journal submission, or during the peer review process. Of those that declared whether they had performed unregistered research or not, 51 (45.5%) participants had previously performed unregistered research. Registrants were most commonly made aware of the Research Registry® through submission to the International Journal of Surgery (IJS) family of journals (n = 57, 47.5%). Survey participants identified the most important features of registration to be its convenience, including the ease, time and cost of registration. Thematic analysis revealed the most common motive for registration to be as a mandatory requirement of journal submission, and that registration can be improved by simplification of the registration process. CONCLUSION: Registries must focus on engaging their network of users to ensure that research registration is a dynamic process. They need to adopt a user-centered and agile approach to their development, with a strong focus on "customer service". Moreover, by working in partnership with journals, it is possible to improve compliance with registration.

Recurrent pancreatitis after unremarkable colonoscopy, temporalised by CT imaging: an unusual case.

Acute pancreatitis is a common surgical presentation, frequently caused by gallstones and alcohol. Here we present an unusual case of a recurrent episode of pancreatitis after an unremarkable colonoscopy, in a patient with several pre-existing risk factors for pancreatitis. Before and after abdominal CT scans clearly demonstrate the acute inflammatory process affecting the pancreas and temporalise its development. Early resuscitation and appropriate involvement of high dependency care is advocated by all current guidelines to improve patient outcome. We consider possible aetiology and how early diagnosis and recognition of possible high-risk situations can expedite its investigation and management, helping to provide the best possible care.

Impact of the mandatory implementation of reporting guidelines on reporting quality in a surgical journal: A before and after study.

BACKGROUND: Journals are an important conduit for the publication of research. However, the reporting quality of research has been shown to be lacking. We sought to determine if reporting quality could be improved by mandating compliance with the relevant reporting guidelines during the submission process to a single surgical journal. METHODS: The policy above was implemented in the International Journal of Surgery (IJS) in March 2013. This involved requiring all authors submitting observational studies, randomised controlled trials (RCTs) and systematic reviews to submit completed STROBE, CONSORT and PRISMA Statement checklists respectively along with their paper, making them available to the editor and peer-reviewers. Articles were analysed in three distinct periods from 2012 to 2014, before and after guideline implementation by two independent teams. RESULTS: Our results show that overall STROBE compliance following implementation of the policy increased by a statistically significant 12% (68%-77%, p = 0.00018). Similarly CONSORT compliance increased (50%-70%) as did PRISMA compliance (48%-76%). The items that improved the most were those providing detail on study design, outcome definitions as well as measurement, how patients and quantitative variables were handled during the analyses and discussing limitations and detailing potential sources of bias. CONCLUSION: Implementing a policy mandating the submission of a completed reporting guideline checklist for observational studies, RCTs and systematic reviews can increase compliance. We advocate this measure for other journals and for other study types.

The First 500 Registrations to the Research Registry®: Advancing Registration of Under-Registered Study Types.

INTRODUCTION: The Declaration of Helsinki 2013 encourages the registration of all research studies involving human participants. However, emphasis has been placed on prospective clinical trials, and it is estimated that only 10% of observational studies are registered. In response, Research Registry® was launched in February 2015; a retrospectively curated registry that is free and easy to use. Research Registry® enables prospective or retrospective registration of studies, including those study types that cannot be registered on existing registries. In this study, we describe the first 500 registrations on Research Registry®. METHODS: Since the launch of Research Registry® in February 2015, data of registrations have been collected, including type of studies registered, country of origin, and data curation activity. Inappropriate registrations, such as duplicates, were identified by the data curation process. These were removed from the database or modified as required. A quality score was assigned for each registration, based on Sir Austin Bradford Hill's criteria on what research studies should convey. Changes in quality scores over time were assessed. RESULTS: A total of 500 studies were registered on Research Registry® from February 2015 to October 2015, with a total of 1.7 million patients enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%), and first-in-man case reports (10.4%). Registrations were received from 57 different countries; the most submissions were received from Turkey, followed by China and the United Kingdom. Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. The Kruskal-Wallis test identified a significant improvement in quality scores for registrations from February 2015 to October 2015 (p < 0.0001). CONCLUSIONS: Since its conception in February 2015, Research Registry® has established itself as a new registry that is free, easy to use, and enables the registration of various study types, including observational studies and first-in-man case reports. Going forward, our plan is to continue developing Research Registry® in line with user feedback and usability studies. We plan to further promote Research Registry® to advance the cause of registration of research, to increase compliance with the Declaration of Helsinki 2013.

Apparent asystole: are we missing a lifesaving opportunity?

The use of ultrasonography is rapidly expanding in emergency medicine. Real-time assessment offers clues to prompt diagnosis and creates opportunities for speedy intervention. We present a case of 'cardiac monitor asystole' that proved to be ventricular fibrillation on ultrasound examination. Uniquely this case demonstrates that this, typically unrecognised, form of ventricular fibrillation responds to desynchronised defibrillation, with restoration of perfusion for approximately 30 min. With increasing access to ultrasound we believe that further research is indicated to determine whether some cases of apparent asystole may best be treated by defibrillation, presenting an opportunity to save more lives than current protocols achieve.