Buket Gundogan

Exosomes as Immunotheranostic Nanoparticles

BACKGROUND Exosomes are small biological membrane vesicles that measure 30 to 100 nm in diameter. They are involved in a wide array of biological activities, such as cell-cell communication, signal transduction, transport of genetic materials, and modulation of immune response. Evidence indicates that they can be used as not only therapeutic agents targeted against disease but also diagnostic biomarkers for pathologic conditions. OBJECTIVE In this review, we endeavor to present exosomes as immunologic agents that can be used as pioneering cancer vaccines to prime the immune system and explicate their therapeutic and diagnostic capabilities. METHODS An extensive literature search for studies that involved the use of exosomes as immunotheranostic nanoparticles was conducted using PubMed, ISI Web of Knowledge, and Google Scholar. Clinical trials that involved exosomes were also compiled by searching the clinicaltrials.gov database. RESULTS In its therapeutic facet of application, exosomes can be used as vehicles for drug or gene delivery. These biological vesicles have been found to have excellent host biodistribution and biocompatibility, issues often presented with gene delivery vehicles. Diagnostically, exosomes may prove to be useful biomarkers that are able to surpass current setbacks of modern diagnostic testing, which include invasive methods. Finally, current evidence has implied that the use of exosomes could form the basis for the development of future cell-free cancer vaccines. CONCLUSION Exosomes have numerous functions, and their double-edged features make the scope of their clinical applications, as both a diagnostic and therapeutic tool, immense.

Tissue engineering vascular grafts a fortiori: looking back and going forward.

Introduction: Cardiovascular diseases such as coronary heart disease often necessitate the surgical repair using conduits. Although autografts still remain the gold standard, the inconvenience of harvesting and/or insufficient availability in patients with atherosclerotic disease has given impetus to look into alternative sources for vascular grafts. Areas covered: There are four main techniques to produce tissue-engineered vascular grafts (TEVGs): i) biodegradable synthetic scaffolds; ii) gel-based scaffolds; iii) decellularised scaffolds and iv) self-assembled cell-sheet–based techniques. The first three techniques can be grouped together as scaffold-guided approach as it involves the use of a construct to function as a supportive framework for the vascular graft. The most significant advantages of TEVGs are that it possesses the ability to grow, remodel and respond to environmental factors. Cell sources for TEVGs include mature somatic cells, stem cells, adult progenitor cells and pluripotent stem cells. Expert opinion: TEVG holds great promise with advances in nanotechnology, coupled with important refinements in tissue engineering and decellularisation techniques. This will undoubtedly be an important milestone for cardiovascular medicine when it is eventually translated to clinical use.

Systematic review of the methodological and reporting quality of case series in surgery

Case series are an important and common study type. No guideline exists for reporting case series and there is evidence of key data being missed from such reports. The first step in the process of developing a methodologically sound reporting guideline is a systematic review of literature relevant to the reporting deficiencies of case series.

The efficacy of the Cook-Swartz implantable Doppler in the detection of free-flap compromise: a systematic review protocol

Introduction The Cook-Swartz implantable Doppler monitors venous or arterial blood flow from free flaps and can detect free-flap compromise. Previous studies have shown that the use of this Doppler can improve detection and salvage rates as it provides an earlier warning than the current method of clinical assessment. Such studies assert that the implantable Doppler is of great value in monitoring free flaps in current microsurgical units. This systematic review aims to compare the efficacy of the Cook-Swartz implantable Doppler in monitoring free-flap compromise against conventional clinical free-flap monitoring techniques. Methods and analysis Various electronic databases will be systematically searched for studies that compare the use of Cook-Swartz implantable Doppler with clinical assessment. The selected studies will then have their titles and abstracts screened by two authors. Articles selected after title and abstract screen will have full text downloaded and the complete article will be assessed for suitability. Once the articles have been selected for inclusion, data extraction will take place. For data analysis, the outcomes of the studies will be tabulated, with descriptive statistics performed as appropriate and the detection rate of the Doppler and clinical assessment will be compared and synthesised where possible. Ethics and dissemination The authors hope to disseminate the findings as widely as possible. This systematic review will be published in a peer-reviewed journal and include a number of recommendations as its conclusion based on the evidence contained within. Given the wide range of specialties now utilising flaps, it will be presented at a wide range of national and international conferences. Protocol Registration in PROSPERO CRD42013005818 The literature search and data extraction went on until 28 January 2014. These steps were revised in line with peer review comments.

Bioabsorbable stent quo vadis: a case for nano-theranostics.

Percutaneous coronary intervention (PCI) is one of the most commonly performed invasive medical procedures in medicine today. Since the first coronary balloon angioplasty in 1977, interventional cardiology has seen a wide array of developments in PCI. Bare metal stents (BMS) were soon superseded by the revolutionary drug-eluting stents (DES), which aimed to address the issue of restenosis found with BMS. However, evidence began to mount against DES, with late-stent thrombosis (ST) rates being higher than that of BMS. The bioabsorbable stent may be a promising alternative, providing vessel patency and support for the necessary time required and thereafter degrade into safe non-toxic compounds which are reabsorbed by the body. This temporary presence provides no triggers for ST, which is brought about by non-endothelialized stent struts and drug polymers remaining in vivo for extended periods of time. Likewise, nano-theranostics incorporated into a bioabsorbable stent of the future may provide an incredibly valuable single platform offering both therapeutic and diagnostic capabilities. Such a stent may allow delivery of therapeutic particles to specific sites thus keeping potential toxicity to a minimum, improved ease of tracking delivery in vivo by embedding imaging agents, controlled rate of therapy release and protection of the implanted therapy. Indeed, nanocarriers may allow an increased therapeutic index as well as offer novel post-stent implantation imaging and diagnostic methods for atherosclerosis, restenosis and thrombosis. It is envisioned that a nano-theranostic stent may well form the cornerstone of future stent designs in clinical practice.

How Can We Address the Publication Bias Against Negative Scientific Study Data

We read with great interest the article by Boorman et al. (2015) on ‘‘The Value of Publishing Negative Scientific Study Data.’’ This article succinctly demonstrates the value of publishing negative results not only in the field of toxicology but also for the scientific community and for human health as a whole. Over the past few years, we have seen an increase in articles discussing this issue, yet there appears to be little shift in accepting and publishing negative data among the scientific community. This opinion piece explores how medical and scientific communities, particularly journals and registries, can play a critical role in paving the way for a paradigm shift in the acceptance of negative data appearing in literature. The article tells us that studies have demonstrated that ‘‘negative results are gradually disappearing from the literature in most disciplines and countries.’’ This is not surprising. Historically and even today, scientists have struggled to publish their data in esteemed journals for lack of novelty or interest. Yet it still remains that negative scientific study data valuably add to the plethora of scientific knowledge. The authors quote scientists and journals being intensely interested in impact factors. This is a very real problem and one which the scientific and medical communities must address. Over the last 10 years, we have seen a dramatic increase in journals launched specifically for publishing negative results or having set sections which do so. This is certainly a step in the right direction, although some areas like surgery still don’t have a dedicated negative results journal. Yet work must still be done to make a substantial dent to the immense positive study publication bias present. We agree with the authors in that journal editors should add an active policy for publishing negative data to their acceptance criteria; however, in practice, this may be difficult to implement, particularly at peer review. We propose that journals specifically publishing negative results or having negative results sections may be a better approach. To this effect, formation of registries which publish all data pertaining to their scientific and medical disciplines should be encouraged and, as this article states, would engender potentially enormous savings in resources. Our group has recently launched the Research Registry, an international database that registers all studies with human participants. In fact, the World Medical Association’s Declaration of Helsinki 2013 (http:// www.wma.net/en/30publications/10policies/b3/, accessed February 2016) provides a strong ethical mandate for registering all types of research studies. It is our ethical duty as individuals in the scientific and medical community to ensure negative studies are accurately and fairly represented in the literature not only for the compendium of scientific knowledge but also for knowing what works and what doesn’t, optimizing resource allocation and wider transparency.

The Academic Surgical Collaborative: Launching a new trainee research collaborative

The first trainee research collaborative (TRC) in medicine began in 1986, when General Practitioners orchestrated a research project for regional trainees [1]. Whilst there has been a proliferation of research collaboratives across the UK, and an increase in the proportion of publications written by collaborative groups [2], TRCs have only become more widespread relatively recently. Multicentre surgical research projects led by trainees [3,4] have firmly cemented the resurgence of the TRC and its role within the surgical profession [5]. The National Research Collaborative website is dominated by the surgical disciplines and at present twenty-nine out of the thirty-seven collaboratives listed are surgically themed [6]. Surgical TRCs are an opportunity for trainees at all levels of experience to develop their research involvement [7]. Junior trainees are supported as their exposure to research and audit increases [8] by more senior colleagues who are able to offer advice and experience. As trainees mature, TRCs can help to identify research questions, assist networking, offer academic support and mentoring, provide motivation to finish work [8] and improve access to funding [9]. TRCs are an educational tool, promote future collaboration, and increase the exposure of trainees at all levels to research and audit [1]. Finally, TRCs allow trainees to learn basic research methodology, to assist in the co-ordination of multi-centre studies, and to recruit willing collaborators from other centres who may otherwise be inaccessible [7]. Bhangu identifies that surgical trainees are highly suited to the delivery of collaborative work; they are regularly in contact with each other, are motivated and desire evidence of involvement in research [10]. However, now we find medical students are leading national audit projects (STARSurg) [10], giving them an early taste of collaborative research. International level, trainee led surgical collaborative projects have also begun to establish [10], with GlobalSurg announcing it had completed patient recruitment for its first endeavour in January 2015 [11]. This short paper describes the establishment of the Academic Surgical Collaborative (ASC); a new TRC. We describe the ASCs positioning within TRCs and its guiding philosophies.

How to apply for the academic foundation programme

The UK Academic Foundation Programme (AFP) is a two-year foundation programme that includes an additional “academic theme” undertaking work in research, management/leadership, or education and teaching activities. The limited number of AFP places makes the AFP application a highly competitive process. This article outlines points to consider when applying for the AFP and successful application strategies. Reviewed by successful AFP applicants, this article provides specific insight into applications to the London Academic Unit of Application (deanery).

How to organize a medical elective.

The medical elective is often considered a major highlight of the medical school experience. However, organizing an elective can be a daunting experience. From selecting a destination, to securing bursaries, the road is fraught with uncertainty. In this article, we provide some guidance on how to successfully organize a medical elective. This includes the selection of the destination; options for research or clinical practice and tips for budgeting and acquiring travel bursaries.

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.