quod

The Evolution of a QUOD Box

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Bespoke, ergonomic and unique to the Quality in Organ Donation (QUOD) biobank, the QUOD sample collection boxes are critical to the transportation of donor blood, urine and tissue collected by nurses and retrieval teams. Sample collections are taken at four different time points across the donor management period, all the way through to the point of organ retrieval.

Manufacture

These custom-made sample collection boxes are assembled by hand and distributed nationally from the Oxford hub by QUOD Technical Assistant, Sophia Ali. Sophia joined the team four years ago and she continues to ensure that the Specialist Nurses in Organ Donation (SNODs) and retrieval teams across the UK are well-stocked with QUOD boxes, as well as other essential resources needed in theatre for sample collection. This can include biopsy punches and other equipment to aid in processing samples in the lab. “The most vital piece of kit which I am responsible for building and supplying across all hospitals in the UK”, she says, “is the famous QUOD box.” Watch a video demonstration of Sophia constructing a QUOD box [here] or read the step-by-step process from Sophia below.

How to build a QUOD box by Sophia Ali

“The QUOD box is made up of several components. You start with the outer box which is initially flat packed. Our vibrant QUOD sticker as well as the receipt and map sticker are applied. At the back of the box, we store the two information sheets, one for Scotland and one for England, Wales, and Northern Ireland along with the consent sticker.”

“Inside the box you will find individual red, green, blue, and yellow foams. Each foam represents a separate component and holds a different sample from the donor. The red foam will hold twelve blood tubes – six EDTA, three Heparin and three SST tubes. All are barcoded to identify the collection at separate time intervals. In the yellow foam you will find the BAL tube, three urine tubes and one (orange top) spleen container filled with RNAlater preservative. The green and blue foams contain the five tissue tubes. In the blue foam, the five tissue tubes are filled with formalin and the green, with RNAlater preservative. We currently collect liver, left kidney (in formalin), right kidney (in RNAlater), ureter, right heart ventricle and left heart ventricle. Each box will contain a worksheet where each sample collection can be recorded, and any variance notes can be added. There will also be DB1 and DB2 collection for blood serum in the preliminary stages of donation. Each box will be labelled with a unique barcode to ensure complete traceability. I also make note of where each box is shipped to via this barcode.”

Shipping

On a typical working day Sophia will respond to e-mail requests from SNODs and regional centres, subsequently building each QUOD box and packaging consumables accordingly, ready for shipping: “Due to demand, I have to make sure I have enough material to fulfil all requests. I aim to complete all requests within two working days”. During her time at QUOD, Sophia has calculated that she has built and distributed approximately 4,250 QUOD boxes since 2019! With the rising cost of consumables in recent years, the cost to produce and ship one QUOD box is currently around £60.00 GBP.

From retrieval to research

Tissue biopsies are stored in two different types of media for transportation to preserve the tissue in the best way possible whilst allowing for the widest variety of techniques to be carried out in future studies. Each sample has a unique identifying barcode which is recorded on the QUOD database to preserve traceability and donor anonymity throughout the whole process. The QUOD database links clinical donor information to these samples, allowing researchers access to samples that meet the requirements of their research.

Evolution

The current design represents years of continual evolution and improvement (as pictured), in accordance with changes to legislation from the early stages of QUOD to today. 2023 marks a ten-year milestone which we have honoured with a new logo that can be seen on each QUOD box.

Sophia remarks how the design is under constant review and has seen major changes in recent years, including changes to tissue collection and corresponding changes to the worksheet. Most recently being the change to kidney biopsies, whereby the biopsy from the left kidney goes into formalin, with the biopsy from the right kidney being preserved in RNAlater. Previously, biopsies from each kidney were divided in two, with each half going into formalin or RNAlater. There have also been changes to the sizes of heart and kidney biopsies over the years, in response to feedback from retrieval teams who collect the samples, researchers who use the samples and results from internal quality assurance audits.

A decade of QUOD marks a time of reflection for the whole team, as we look back on the evolution of the biobank over the last ten years and think about all the people who have helped us reach this landmark. We look forward to celebrating this achievement with our wider QUOD family throughout the year and most especially at our symposium on Friday 8th December 2023 at Exeter College in Oxford.

British Transplantation Society 2023

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From QUOD to Scotland: QUOD travelled to Edinburgh for the 50th anniversary of the British Transplantation Society (BTS).

In March, QUOD Research Assistant, Dr Hannah McGivern and Technical Assistant, Sophia Ali journeyed up to Edinburgh for the Joint Congress hosted by the British Transplantation Society (BTS) and NHS Blood and Transplant (NHSBT). This year, delegates were able to celebrate the 50th Anniversary of the BTS and showcase the latest developments in the fields of organ donation and transplantation.

The conference provided a great opportunity to speak with so many of our colleagues from across the QUOD consortium, including Specialist Nurses in Organ Donation (SNODs), retrieval teams, clinicians and researchers, answer questions and listen to feedback.

When asked about her experience after attending her first conference as a representative of QUOD, Sophia commented on how great it was to meet the wider QUOD network: “I communicate with all the SNODs and NORS teams through e-mail, so meeting them in person was lovely. They gave lots of positive feedback about QUOD and how it has been working well over the years in donor hospitals. SNODs enjoy being part of the process and knowing how the work we do day to day can bring forward some ground-breaking research. It was great to speak to the people who handle the QUOD boxes after I have shipped them, to hear what their roles are in QUOD and to listen to them speak about their own personal experiences during the many stages of the QUOD sample collection process. They were also incredibly surprised that each QUOD box that they have handled is built by me!”

QUOD was honoured to be included in the opening keynote lecture on ‘Predicting the Future – Technologies to Inform Organ Utilisation’ delivered by Professor Menna Clatworthy, University of Cambridge. Furthermore, we were delighted to meet with healthcare professionals and researchers who have utilised QUOD samples as part of their research studies that were presented at the congress.

On the final day of the conference, QUOD Principal Investigator, Prof Rutger Ploeg and Basic Science Co-ordinator, Dr Maria Kaisar delivered a presentation as part of the UK Organ Donation and Transplantation (ODT) Research Network session, acknowledging the ten-year accomplishments of the biobank as well as recent collaborations and exciting new developments.

New QUOD Colleague Questionnaire

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Dr Ana Gil-Bernabe – Quality & Governance Manager for QUOD and QUANTUM Biobanks

What were you doing most recently before joining QUOD?

I worked in the Human Tissue Governance group, which is part of RGEA (Research Governance, Ethics and Assurance), within Research Services at the University of Oxford. This was a research support role focused upon ensuring that work with human tissue at the University of Oxford is performed in compliance with the UK legislation and the Human Tissue Licence conditions. Basically, the aim was to allow the progress of science within the legal and ethical boundaries that regulate clinical research.

What interested you about working with QUOD?

During my time in the Human Tissue Governance group, I interacted with the eight biobanks that operate under the main Human Tissue Licence at Oxford, including both QUOD and OTB. This was a great opportunity to understand what a fantastic research resource biobanks are for researchers, here and abroad, and how they optimize their very valuable samples that are donated to the biobanks. QUOD is a fantastic example of national and international collaboration, with samples collected and delivered to multiple sites. I understood that it was a great opportunity to apply my acquired knowledge on human tissue governance and quality assurance, as well as to progress on my knowledge on human tissue biobanks and their governance. Last, but not least, I do have a passion for research (I have been a researcher for about 15 years) and the field of transplantation is very close to my heart.

What does your role in QUOD involve?

In a nutshell, ensure that QUOD adheres to the legal and ethical frameworks that regulate clinical research in the UK, in particular the Human Tissue Act 2004, and to the conditions of the Human Tissue Licence at the University. QUOD Governance is transitioning to a Quality Management System, iPassport, to make this task easier, and part of my role will be to support this transition. We will use iPassport to manage our governance documents, run audits, report non-compliances and keep training records, for example. I will also support compliance with other frameworks that relate to clinical research, such as the Health Research Authority or the Research Ethics Committees.

Lightning round time:

If you were stuck on an island what three things would you bring?

  • Documents, of course, any activity needed would be well described in the relevant Standard Operating Procedures (SOPs);
  • iPassport, of course, all those documents will be accessible through iPassport;
  • Nothing else, I love the sea, so I’d enjoy the opportunity to swim and explore the island.

Where’s your favourite place?

It could well be that island, but probably my hometown, Cadiz, as it not only has a lovely coast, but also all the ingredients for happiness: family, friends, good weather and good food. In its absence, any place near the sea, with the sound of the waves and the smell of the salty water.

Finally, what kinds of enquiries should people bring to you, and how best can they reach you?

Anything to do with governance and quality assurance: documents (SOPs, Risk Assessments, Working Instructions), audits, non-compliances and training records, for example. As we transition to iPassport, I imagine many questions will be related to the use of this system.

You can reach me at ana.gil-bernabe@nds.ox.ac.uk and I’m setting up other ways of communication, using Planner and Teams – more information to come!

QUOD & Evotec: An academia-industry partnership built on complementary strengths

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Tobias Bohnenpoll, Evotec SE

Evotec SE and the University of Oxford have recently renewed their collaboration agreement, reflecting a robust and sustainable partnership to profile tissue biopsies collected, processed and stored by the QUOD programme. Through this partnership, Evotec has already generated genome-wide bulk transcriptomic data from about 2,000 donor biopsies (895 kidney and 910 liver), complementing the rich clinical records and technical metadata collected by NHSBT and QUOD. Evotec is currently extending the analysis to heart biopsies and high-resolution single cell and spatial transcriptomics, which will allow in-depth molecular characterisation of tissue microenvironments. Together, we aim to generate mechanistic insights to improve the quality of organ donation and transplantation, and to identify targetable mechanism of injury and repair that will open new avenues for therapeutic intervention and patient stratification in metabolic, cardiac and renal diseases.

The multimodal characterisation of organ biopsies using state-of-the-art, high-throughput analysis is an important cornerstone of Evotec’s Molecular Patient Databases (E.MPD), an industry-leading, proprietary collection of curated human datasets for translational research and patient-centric target and biomarker discovery. However, the integration of complex clinical and molecular data into curated multidimensional datasets poses great challenges to scientific teams and requires interdisciplinary approaches. Evotec and QUOD researchers have assembled an expert team that efficiently combines domain knowledge in medicine and biology with high-throughput molecular analysis and modern data science. Together, we are exploring the complex relationships between biopsy molecular profiles, donor and recipient clinical phenotypes, and graft outcomes in all major organ recovery and transplant conditions. This exploratory analysis of biopsy transcriptomes involves unsupervised clustering, dimensionality reduction and embedding of clinical data and molecular signatures to enable a data-driven hypothesis generation.

Importantly, the multidimensional characterisation of QUOD biopsy transcriptomes has enormous potential beyond research in organ donation and transplantation, with direct applications in modern drug discovery. First, samples from healthy organ donors that are obtained from the Oxford Transplant Biobank (OTB) can serve as reference for the molecular analysis of other disease-focused prospective cohort studies, which often lack appropriate controls. Second, organ donors often present with early, subclinical disease phenotypes that potentially provide unique insights into the onset and early progression of metabolic and other common diseases. For example, Evotec has integrated a data-driven selection of QUOD and NURTuRE (National Unified Renal Translational Research Enterprise) kidney biopsy transcriptomes ranging from healthy to end-stage chronic kidney disease to model disease initiation and progression at the molecular level. We are also combining transcriptomic analysis with AI-assisted digital pathology to characterise liver biopsies for steatosis, inflammation and fibrosis and determine their position along the spectrum of fatty liver disease.

Ultimately, these systems biology approaches aim to positively impact the lives of patients with organ transplantation, cardiometabolic diseases and related complications by leveraging advanced molecular analysis and interdisciplinary expertise. This transformative work is only possible through close collaboration between academia and industry, combining their strengths and resources to achieve meaningful advances in knowledge that will help improve patient care and therapeutic intervention.

Announcing the ‘6th National QUOD Symposium’.

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We are excited to announce that the annual QUOD Symposium is back and will be held on Wednesday 9th November 2022 at Jesmond Dene House in-person, in Newcastle.

We look forward to having the opportunity to meet with the extended QUOD family based at regional centres and donor hospitals across the UK, as well as with researchers from academia and industry, and our NHSBT colleagues. Please see below for our save the date poster and latest programme.

If you are interested in joining us, please RSVP to quod-research@nds.ox.ac.uk

British Transplantation Society Conference 2022 debrief – by Azita Mellati

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After a year of virtual meetings and conferences, this year the British Transplantation Society (BTS) congress was again held in person at the ICC Belfast. The conference provided a great opportunity for clinicians and researchers to meet up and share the latest about their research and developments on their projects. Over the 3 days of the conference including 31 sessions, more than 100 talks were presented.

Our team from the Nuffield Department of Surgical Sciences (NDS) actively participated in the conference with a total 3 presentations and 1 poster. Dr Mohamed Elzawahry and Dr Letizia Lo Faro presented their research work on “Safety and feasibility of oxygenated hypothermic machine perfusion in the preservation of donor organs for pancreas transplantation” and “Normothermic machine perfusion of the liver supports protein translation and mitochondrial function while reducing protein degradation and metabolic imbalance: a proteomics study” in the “Dragon’s Den” and “Medawar medal presentations” sessions, respectively. The poster titled “Evaluation of kidney injury after treatment with CC-4066 during cold storage and assessment during normothermic reperfusion in a porcine ischemia reperfusion injury model” by Ms. Pommelien Meertens (as part of her Research Internship at NDS) was presented during the conference as well. I also had the opportunity to present my own research on “Investigation into the effect of Alpha-1 antitrypsin delivered via different preservation methods on ischemia-reperfusion injury in pig kidneys” as part of the “Science oral presentations” session. I received very interesting feedback on my project and had the great fortune to discuss details and plans with the audience and other attendees.

In addition to the scientific part of the conference, we also had the opportunity to enjoy and come together to celebrate the 50th Anniversary of the BTS. Over the course of the Gala Dinner themed “the 70s”, members shared good laughter and created wonderful memories. The conference also provided the opportunity to acknowledge and celebrate the lifetime of research work of several members of the BTS, including Professor Peter Friend from within our own department. Overall, this year’s BTS congress was a major success and a great sign that in person, scientific gatherings are back again for the better.

New QUOD Colleague Questionnaire: Dr Meng Sun – Data Co-ordinator & Analyst

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What were you doing most recently before joining QUOD?
Before joining QUOD, I was a genetics data analyst working at a public body following previous experience as a post-doctoral researcher at the University of Oxford.

What interested you about working with QUOD?
I have always liked working with data, databases and statistics. Being a data manager and having the opportunity to do research at the same time sounded like a good combination. QUOD’s position is also attractive because here we are working in an important area – organ transplantation. What we do really matters for patients.

What does your role in QUOD involve?
My main duties include managing databases for QUOD and OTB (Oxford Transplant Biobank) and their web applications, working with researchers on sample selection and data analysis. I also attend various meetings to provide statistics and advice related to databases and research.

Lightning round time:

If you were stuck on an island what three things would you bring?

  • a sharp knife for hunting and cooking;
  • a box of matches to make fire;
  • a tent to live in.

Where’s your favourite place?
Port Meadow, Oxford which is huge, a good place for running or just wandering.

Finally, what kinds of enquiries should people bring to you, and how best can they reach you?

Please contact me if you would like to know more about the samples we have in QUOD and how they could be used for your research. The best way to reach me is by my email meng.sun@nds.ox.ac.uk.

Spotlight on a QUOD Colleague – Dr Bill Scott

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For this edition of the QUOD newsletter, the spotlight shone on Dr Bill Scott who is the Scientific Director of Transplantation and Regenerative Medicine at Newcastle University, liaising with colleagues in all transplant specialities, orchestrating the daily running of the labs with a focus on moving basic and translational research into clinical practice. Bill is a key member of the QUOD hub in Newcastle, formed during the MRC funded expansion of QUOD to include whole organs made available for research. This important steppingstone will form the basis of many more research projects and enable access to bespoke samples to help answer burgeoning questions posed by the wider transplant community.  

Bill has spoken of his interest in improving access to tissue for research purposes, which has led to his collaboration with QUOD. He commented on how QUOD is uniquely positioned to address fundamental questions by facilitating access to blood, urine and tissue samples which are intrinsically linked to details of the donor. When asked what he thought was the biggest hurdle facing sample accessibility, he highlighted the importance of effective communication between all parties concerning consent and regulation at the start of the retrieval process. “As we leverage new techniques” he said, “we need to consider how we communicate this [information] to a lay audience”.

Bill has many more strings to his bow, which I was delighted to discuss with him. Originally hailing from the United States, Bill recalls his aptitude for maths at an early age, entering maths competitions when at school. He later undertook an undergraduate course in engineering at Ivy League University, Cornell, which also included core biology modules in addition to maths and engineering. These early studies underpinned his combined interest in medicine and engineering; after all, an engineer is adept at problem-solving, and throughout his postgraduate and doctoral training in Minneapolis in biomedical engineering, it became evident to him that the fundamentals of engineering could be applied to help solve problems in the clinical sphere. His interest was piqued by organ donation and transplantation research where there were, and still are, a number of issues to tackle, all with the common goal of helping clinicians and improving transplant outcomes for patients.

The NHS relies on companies making reasonably priced and accessible devices to help healthcare professionals deliver expert care to their patients. Bill highlighted the problem that many products are not affordable and are manufactured in the United States with the US reimbursement model, which differs completely from that of the UK and Europe. New devices developed on the back of high-quality research must serve real-world needs as well as make a profit for investors. Sounds like a tall order, right?

With this in mind, Bill took his years of research and learning a whole new vocabulary to approach and pitch to investors, sought to develop a device that could address key issues raised by the transplant community. At present, the demand for organ transplants far exceeds the supply, and current preservation systems rely on static cold storage which cannot be relied upon to keep the donated organ in optimal condition for more than a few hours. Methods that can sustain optimal conditions for prolonged periods of time are too large, complex and expensive. Bill, in collaboration with clinical engineers, software developers and investors, have developed the ScubaTx device designed to be fit for the real-world transplant environment and automate as much of the process as possible, while providing feedback on key events for the surgical team who can focus their attention on the transplant procedure rather than setting up a machine. Funds have been raised through Innovate UK and currently a number of prototypes are going to stakeholders across the world, with the hope that one day in the near future the device will be suitable for commercialisation. 

Over the years, Bill has also successfully acquired financial backing for several start-ups and research projects. When asked what advice he would give to early career researchers and future entrepreneurs looking to write their own grant proposals, he emphasised the need to just put yourself out there. “You miss out on 100% of opportunities you don’t try for, [and] it takes 100 times of repeating the same task to get good at something” he said. Essentially, persistence and resilience are key. Bill also advised to “not limit yourself to one funder” and take time to understand what motivates the funder, as they will each want something different. He continues by describing the continual evolution of a grant proposal, adapting to the feedback received and the importance of finding the right investors and stakeholders who share your vision.

Bill can often be found in front of an audience of another kind as he leads the MRes Transplantation course as a Senior Lecturer and Associate Professor. He says it is a very rewarding experience as he gets the opportunity to inform, inspire and foster greater progress and interest in the field in the next generation of nurses, healthcare professionals and researchers, all of whom form the backbone of the NHS. For Bill personally, teaching also gives him the chance to re-connect with his specialist field, to see the bigger picture and highlight problems that face the current generation.

When asked what piece of advice he would give to his students and mentees, he highlighted the importance of forming a narrative, regardless of whether you are creating a poster, presentation or producing written work like a grant proposal or manuscript, “if you do not tell a story, then you are simply stringing together a series of facts on the screen or on paper, expecting others to read the situation exactly as you do”.

When Bill is not teaching, presenting or working in the lab, he enjoys hikes in the countryside with his dogs and fishing, where he can embrace the tranquillity and explore the natural beauty of Northumberland.

Dr Bill Scott was interviewed by Hannah McGivern

QUOD named UK Biobank of the Year 2022!

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The UKCRC Tissue Directory and Coordination Centre awarded QUOD first place in the UK Biobank of the Year.

The UK Biobanking Showcase is the UK’s leading event for those who work in biobanking and human tissue research and took place online over three days with interesting talks and presentations from biobanks all over the UK.

Please see below some extracts from the Judging Panel’s comments: 

‘… the Biobank provides a highly specialist resource which is of immense value to the organ donation field.  Despite being so specialised, … QUOD nevertheless responded flexibly during the pandemic to participate in the RECOVERY trial and in the development of the NHSBT Oxford COVID BioArchive (COBA).  …  The panel particularly commended the quality and range of the Biobank’s outreach and engagement activities which unusually included providing work experience to college students during the pandemic.’

Professor Ploeg, Director of QUOD (Quality in Organ Donation) and Dr Sarah Cross National Operational Coordinator of QUOD are delighted with this wonderful achievement: ‘This award is an important milestone in our pursuit to increase research in donation and transplantation, increasing organ utilisation and providing more and better organs for our patients’. They congratulate the whole QUOD team including the Specialist Nurses in Organ Donation and NORS teams based in the 61 NHS partner trusts across the UK, as well as the core team in Oxford, the Directors of NHS Blood and Transplant, the Medical Research Council and our academic collaborators without whom none of this would have been possible.