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Take a look at a selection of our recent media coverage:
23rd January 2025
Women are waiting longer for lung transplantation than men, a French retrospective study finds, showing changes to clinical guidelines and policies are needed to address gender inequalities.
Lung transplantation is a highly dynamic segment of solid organ transplant, where gender is known to play a central role, the study authors wrote in ERJ Open Research.
Previous research using US lung transplantation data had found women had a lower chance of receiving a transplant than men and waited longer before transplant.
For this study the authors evaluated the differences between men and women before transplantation, during and immediately after surgery and in the months and years following transplantation using data from the French Cohort in lung transplantation (COLT) database – the first to analyse all three periods of the transplantation pathway.
Overall, 1,710 participants (802 women and 908 men) were included in the study, with analysis showing women waited an average of six weeks longer for transplantation, spending 115 days on the transplant list compared with 73 days for men.
Women were less likely than men to undergo transplantation (91.6% vs 95.6%), the data showed.
At the time of registration on the lung transplant list, women were younger than men (47 years vs 54 years) and they displayed fewer comorbidities, including ischemic heart disease and cardiovascular risk factors.
In both genders, the main underlying disease was COPD/emphysema, followed by cystic fibrosis and interstitial lung disease.
In other differences, pre-transplant anti-human leukocyte antigen (HLA) antibodies were more prevalent in women than in men (46% vs 26%) for both class I and class II, with the number of pre-transplant class I anti-HLA antibodies associated with an increased waiting time.
It was also more common for women to receive lungs from height- and sex-matched donors, despite higher female-waiting list mortality and a higher proportion of male donors, the authors wrote.
They stressed that women with oversized lung transplantation, defined by predicted total lung capacity ratio and weight, did not have worse survival, therefore suggesting that size matching criteria could be less stringent.
Post-transplantation, women had a significantly higher survival rate than men, with 34.4% of female recipients dying compared with 42.7% of male recipients.
Survival rates were also higher among women than men at five years post-transplantation (70% vs 61%).
Study lead author Dr Adrien Tissot of from the Pulmonology Department at Nantes University Hospital, France, said people on the lung transplant waiting list had a poor quality of life and high mortality risk.
‘For these patients, waiting is suffering, and the longer the wait the worse these women are suffering,’ he said.
‘Clinicians, patients and policy makers must acknowledge this gender difference as it’s essential for appropriate action to be taken.’
Dr Tissot suggested early listing for women or revising the allocation policy of donor lung to recipient could be considered.
‘We believe our findings, such as the potential role of size matching and its consequence on access to lung transplantation, and length of time on the waiting list, may also apply in other countries where lung transplantation is performed,’ he said.
Also commenting on the findings, Dr Michael Perch, chair of the European Respiratory Society’s Group on Lung Transplantation and a senior consultant at Rigshospitalet in Copenhagen, Denmark, said there could be several reasons why women waited longer for transplantation, including differences in education and health literacy, socioeconomic differences, immunological factors and donor-recipient size matching.
‘Clinicians and policymakers alike must question why there is a focus on gender and size matching in transplantation when evidence shows that, in lungs, these factors do not determine a woman’s chance of survival, and it ultimately risks an increase of women dying while waiting for a transplant,’ he said.
‘It is unacceptable for women to be waiting longer than men for these lifesaving donations, so effective corrective measures must be introduced.’
3rd October 2024
European Donation Day, taking place on 5 October 2024, is an opportune time to acknowledge the remarkable progress being made in organ donation and transplantation in Europe and to discuss how to accelerate further achievements. Here, Dr Chloë Ballesté Delpierre, elected member of the European Society for Organ Transplantation Council (ESOT), shares her thoughts.
Organ transplantation is one of modern medicine’s most significant milestones, providing life-saving treatments to countless individuals. However, significant disparities persist in access to these procedures, leaving many without the care they need.
The number of patients receiving transplants in Europe varies widely, from 114.8 per million in Spain to just 7.6 in Bulgaria in 2019 – a stark disparity.1 As technological advancements and innovations like bio-artificial organs continue to transform patient care, they also underscore the challenge of preventing these inequities from widening.2
The 2023 Global Convergence in Transplantation Summit marked a significant step toward addressing such disparities, highlighting the critical need to standardise practices and ensure equitable access for all.3
Successful programmes in Spain, Portugal, Italy, Croatia and the UK provide valuable lessons for developing a blueprint for best practice throughout Europe. The deceased organ donor rate can also be used to evaluate successful practice, measured per million of population (pmp) in 2023.4
Spain’s programme with 49.38 deceased donors pmp, is regarded as a global benchmark.4 The country excels due to its robust three-tiered governance structure: specialised doctors in organ donation, a comprehensive reimbursement strategy and strong media collaboration.5
This structure, covering national strategy, regional coordination and hospital-level donor management, is key to its success and Spain’s commitment to innovation, including donation after circulatory death and expanded donor criteria, further strengthens its leadership in this space.5
Portugal with 37.13 deceased donors pmp is catching up with Spain and emerging as a global leader in organ donation.4 Of note is how Portugal capitalised on its close geographical, governmental and cultural ties with Spain to foster collaboration and knowledge exchange, which significantly strengthened its own organ donation and transplantation system.6 Other key strategies include a focus on tertiary prevention, reforms in dialysis governance and sustained financial commitment.6
Italy, with 29.39 deceased donors pmp,4 has developed a robust organ donation system coordinated by the National Transplant Network, with legal frameworks, cultural integration of altruistic donation and a national training strategy that has increased donation rates.7
Similarly, Croatia has built an efficient national transplantation network, with strong central governance, collaboration and resource-efficient management that ensures sustained excellence in organ donation practices.8 In Croatia, Spain, Portugal and Italy, intensive care doctors are also actively involved in organ donation.5-8
In the UK, organ donation and transplantation have seen significant progress, with 1,510 deceased donors (22.35 pmp) and 938 living donors in 2023/24, enabling 4,651 transplants – a 6% increase in deceased donors and a 3% rise in transplants from the previous year.9
The UK’s success stems from its integration of research with clinical practice, donor coordinators and impactful public awareness campaigns. These efforts are supported by robust funding structures and significant investments in infrastructure and technology.9
On the other end of the spectrum, Greece lags behind its European counterparts with 8.45 deceased donors pmp4 and an urgent need for systemic reform. The Onassis Foundation recommends establishing an independent national transplant organisation with strong governmental backing, implementing a ‘soft opt-out’ consent policy, integrating donor specialists in hospitals and focusing on public trust and education.10
Based on the success of Spain, Portugal and the UK, key priorities for Greece include expanding infrastructure, standardising the organ donation process, improving reimbursement systems and emphasising patient-centred care.10 A dedicated task force is advised to oversee these complex reforms.
To effectively build on the successful programmes described in this article, other countries must adapt these best practices to their unique cultural, legal and healthcare contexts.11
A flexible and aligned approach that balances local needs with European standards is required, along with collective efforts to close the gaps in organ donation and transplantation.
A recently developed 16-domain conceptual framework offers a comprehensive guide for developing and evaluating national programmes, focusing on responsiveness, efficiency and equity.12
This framework promotes a standardised approach that considers the diverse realities across jurisdictions, ensuring that all patients, regardless of their location or socio-economic status, benefit from the latest advancements in transplantation technology. This serves as a strong example, but additional initiatives across Europe are required to standardise clinical practices and ensure equitable access to transplantation.
ESOT is actively collaborating with the World Health Organization, among other stakeholders, on this matter, with a strong dedication to continuing the efforts to bridge the gap in Europe.
By working together, we can create a more equitable system, extending the benefits of organ transplantation to every corner of Europe and addressing disparities that hinder progress.
7th August 2024
The new EU-funded LEOPARD project aims to transform liver transplantation by leveraging artificial intelligence to better stratify patients waiting for life-saving surgery. Here, Professor Christophe Duvoux, LEOPARD project coordinator, discusses the current state of liver transplantation in Europe, how the project aims to overcome the challenges and its anticipated impact on clinical care and patient outcomes.
Liver Electronic Offering Platform with ARtificial Intelligence-based Devices (LEOPARD) is a pioneering, EU-funded initiative in liver transplantation, uniting stakeholders across Europe to revolutionise organ allocation strategies for individuals with decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC).1
Liver transplantation is the only lifesaving option for patients with end-stage cirrhosis and early, moderately advanced HCC,2 accounting, on average, for 50% and 35% of liver transplantation indications, respectively. However, its efficacy is hampered by significant challenges related to organ shortages and increasingly limited allocation models.3,4
With only 5,000 liver transplantations performed across Europe annually,5 compared to 12,000 patients on waitlists, there is fewer than one liver graft available for every two patients. The consequence? Among patients currently listed for liver transplantation in Europe, waitlist mortality and dropout averages 15-20%, with large disparities across European countries.1
Continued reliance on the Model for End-Stage Liver Disease (MELD) score to prioritise transplantations is hindering progress within the liver transplantation landscape. Originally devised over two decades ago for a different patient demographic, the MELD score was designed to limit waitlist mortality risk in patients with DC but now falls short in addressing the complexities of today’s patient population.
This score, which hinges on three biological predictors – creatinine, bilirubin and International Normalised Ratio – fails to adequately capture the 21st century DC and HCC patient, many of whom are older, living with multiple comorbidities, or are in intensive care settings.
Approximately 25-30% of DC patients receive organ transplants based on extra MELD points, while there is currently no applicable predictive model for waitlist dropout for HCC patients.3,4,6 HCC patients are often prioritised through MELD exception rules, as their lab MELD scores do not encapsulate their transplant urgency.
The reality is stark. Overall, only 30-40% of transplant candidates are allocated organs based solely on their true lab MELD scores. This system needs an urgent overhaul to ensure fair and accurate prioritisation, enhanced patient outcomes, and reduced waitlist mortality.
Aligned with the ‘Horizon Europe HLTH 2022 tender, Tool 12 01: Computational models for new patient stratification strategies’ – a funding call under the Horizon Europe programme aimed at advancing healthcare through the development of innovative computational models to improve patient categorisation based on risks and needs – the LEOPARD project seeks to address these challenges and to unlock the potential of artificial intelligence (AI).
The project focuses on developing and validating an AI-based predictive algorithm that surpasses current prioritisation models and accurately stratifies both DC and HCC patients by their risks of waitlist mortality or dropout. This will be achieved by:1
LEOPARD’s backbone is a robust consortium of major European Organ Sharing Organisations (OSOs), clinical research experts, research labs, small or midsize enterprises, patient organisations and scientific societies including the European Society for Organ Transplantation (ESOT).
Some 50 liver transplant centres across seven European countries will contribute to a dataset of 3,000 patients with DC and HCC – data that will inform the development of advanced predictive models using machine learning techniques.
Validation will occur through real-life prospective cohorts of 1,500 patients, supplemented by a cohort of 600 patients with bio- and imaging banking. Simulations will assess the impact of LEOPARD predictive algorithms on graft allocation and patient outcomes.
Critically, LEOPARD will produce outputs that can be used in clinical practice, including:1
LEOPARD presents an unprecedented opportunity to unite the liver transplantation community around a robust European initiative. By leveraging cutting-edge AI and collaborative expertise, LEOPARD has the potential to significantly improve patient outcomes, harmonise prioritisation schemes across Europe and advocate for equitable access to lifesaving liver transplantations. This project promises immediate clinical applications and opens new research perspectives, envisioning a future with improved waitlist mortality or dropout to compensate current organ allocation inefficiencies.
Professor Christophe Duvoux
LEOPARD project coordinator and full professor of hepatology and head of the Medical Liver Transplantation Program at Mondor Hospital, Paris, France
27th June 2024
The opportunity to transform patient care using robotic techniques for lung transplantation is being championed and embraced at Vall d’Hebron University Hospital, spearheaded by Dr Albert Jauregui. Here, with an introduction from Helena Beer, Dr Jauregui discusses robotics within the context of complex lung surgeries, his increasing experience with this technique as well as the benefits and challenges he’s identifying and addressing, and the promising future of this enhanced surgery.
For many clinicians, the opportunity to support patients through a difficult time in their lives and have a profound and enduring impact on their health and wellbeing is a key reason for joining the profession, and transplantation is arguably one of the fields in which this can be achieved most acutely.
This was certainly among the determining factors in Dr Albert Jauregui’s career choice. ‘I decided to dedicate myself to thoracic surgery because it is a very attractive specialty within the field of surgery [as] you have many possibilities to help patients,’ he says.
As chief of the department of thoracic surgery and lung transplantation at the Vall d’Hebron University Hospital in Barcelona, Spain, Dr Jauregui is the driving force behind the adoption of medical technologies that have been making significant advances in the field so that his team can make an even bigger impact on clinical care and patient outcomes.
Robotically assisted, minimally invasive surgeries for lung cancer have been undertaken at the hospital for several years, but lung transplantation has still required aggressive surgery, which is something that Dr Jauregui is keen to change.
In 2023, his team performed Spain’s first two robotically assisted single-lung transplants, with both patients showing good improvement in the postoperative period and needing only mild pain medication after surgery – an outcome that the team is very happy with.
Bilateral lung transplants are next on the agenda, and Dr Jauregui and his team plan to perform five of these robotically assisted procedures this year and 10 in 2025 to build up the bank of evidence and continue working towards offering this type of innovative surgery to more patients.
Although the pool of lung donors has increased in recent years, thanks partly to relaxing the acceptance criteria and allowing new types of donors, the number still needs to be improved. The most important thing is to ensure a correct match between donor and recipient based on blood typing and immune characteristics to avoid organ rejection.
It is also essential to consider the graft size because large lungs can cause spatial problems in small thoracic cavities, and small grafts can be related to chronic dysfunction in the recipient. Therefore, it is crucial for lung transplant teams to try to find the best recipients for each donor.
Lung transplantation itself is considered one of the most complicated transplantation procedures due to the unique characteristics of the lungs – they are the only solid organs that have contact with the ‘outside world’ through breathing. Technically, it is a challenging surgery requiring collaboration with a large, experienced, multidisciplinary team to ensure the best results.
Lung transplant recipients are also particularly susceptible to infections and require high doses of immunosuppressive medications under strict control to avoid graft rejection and boost their immunity.
Thoracic robotic surgery has had a great impact on patients, especially in lung cancer where we see that its progress is unstoppable. The technical improvements offered by robotic surgery provide the patient with benefits in terms of recovery after surgery that are much better than traditional surgery.
Furthermore, the accompanying surgical precision makes the robotic technique extremely useful in lung cancer and transplantation and, thanks to the great experience of our transplantation team, we felt it had to be a logical evolution towards less aggressive and more precise surgeries.
Patients awaiting a lung transplant are usually significantly weakened and are traditionally offered a very aggressive open technique.
Our team performed robotically assisted surgeries with synthetic lungs in the lab before moving to large animal models. It was found that by deflating the lung and relying on the skin’s flexibility, we could use a smaller incision below the sternum to remove and insert the lungs.
Now, with the incorporation of robotic surgery for this type of patient, we have been able to reduce surgical aggression with preliminary results showing a substantial improvement in their recovery after a lung transplant.
The technique is still in its infancy and it’s at too early a stage to be able to operate on all the patients who are on the waiting list for a lung transplant using robotic surgery. Recipients tend to be a very heterogeneous patient group, but we are sure that in the very near future, it will become the surgical technique of choice.
As it is a surgery performed with small incisions and minimal invasion, the healing process will, of course, be quicker and less painful. This is especially beneficial because, as already said, these patients are usually frail due to the nature of their disease. Providing care in the least invasive way possible can only bring better results.
Robotic procedures account for 3% of all lung transplants performed at our centre. The technique is already defined, but greater patient numbers are needed to demonstrate its differences compared with traditional methods.
Our team will perform more robotic lung transplants each year, but it will take time to reach definitive conclusions. For now, the results regarding recovery and postoperative pain are encouraging. Patients who undergo robotic surgery need less analgesia and recover faster, but we still cannot reach absolute conclusions.
The most significant limitation is the widespread differences seen in terms of disease and degree of severity for patients on lung transplant waiting lists. As robotic lung transplantation is a very new technique, it requires performing a larger number of procedures and greater experience to generalise its use in more patients.
Another area for improvement is the surgeons’ experience with robotic surgery procedures themselves. Robotic surgery is increasingly being used, but it is still not widespread in general thoracic surgery programmes, and even less so in lung transplant programmes.
However, the worldwide interest in our findings in Barcelona makes the future promising, and we hope that more thoracic surgeons will join the movement.
This technology will undoubtedly improve in the future with the advent of more precise and even less invasive platforms. We are sure that organ transplants will become increasingly robotic in the future.
18th March 2024
Speaking at Hospital Healthcare Europe’s Clinical Excellence in Respiratory Care event, Professor Paul Corris discussed the milestones and remaining limitations of lung transplants, what non-transplant physicians can do to help support these patients, and how a lack of usable donor lungs is being addressed with impressive innovations and results.
Having been at the forefront of the transition of lung transplantation from an experimental procedure to routine therapy, Professor Paul Corris’ contribution to respiratory medicine is unparalleled, and not just in the UK but worldwide. What he doesn’t know about lung transplantation isn’t worth knowing.
Co-author of all the major guidelines in the field and on many key clinical trials and original research, the emeritus professor of thoracic medicine at Newcastle University and the University of Oxford, UK, has made it his mission to champion the critical importance of respiratory physicians in the management of lung transplant candidates and recipients.
Indeed, as he says, ‘the gradual improvement of lung transplant techniques was very much based on the teamwork of surgeons, physicians, microbiologists, technicians and nurses, all working together’.
And this teamwork is more important now than it has ever been as new innovations are increasingly being adopted and revolutionising the field.
If we go through the milestones, it’s interesting that vascular anastomosis was all done and dusted in the 1930s but airway anastomosis was a problem. In the 1940s and 50s, work to try and improve bronchial anastomosis was carried out and the first human lung transplant attempt was actually in 1963 before the first heart transplant.
After that, something like 40 attempts were recorded in the literature, all of which ended in abject failure. So, there was a very uncertain start to lung transplantation.
Interestingly, the first success actually came via a heart-lung transplantation in 1980 for a patient with what was, in those days, called primary pulmonary hypertension, now known as idiopathic pulmonary hypertension.
Although successful lung transplantation started with a heart-lung transplant, overall, there are only around 3,000 heart-lung transplants that have been carried out, whereas we’ve now got a world experience of around 70,000 lung transplants.
Lung transplantation is now a fully validated clinical treatment and improves both survival and health related quality of life for patients in terms of exercise tolerance and symptoms and functional class.
Data shows the functional status of surviving patients at five years and 80% of patients were in functional class one or two. In other words, really living normal lives. And I think this is a very important take home message: not only are we prolonging life, but we’re transforming the quality of life. And there’s very good data showing that this procedure has a dramatic impact. Patients can not only return to normal sedentary life, they can return to very active life, and this is the goal of what we’re seeking to achieve.
Generally, surgical techniques for transplants have not changed since the early 1990s but in modern times, there’s a favourable move towards undertaking bilateral lung transplants rather than single lung transplants.
Now, that does have a knock-on effect in the sense that in the past a donor with two potential lungs for transplantation could be used for two recipients, whereas if you’re going to put both lungs into one recipient, it halves the number of patients who may benefit and that’s an issue for us.
The choice for surgery now is that a single lung transplant is used principally for patients where there is a low risk, either through infection or from leaving that native lung behind and, in our view, that should be selected patients with lung fibrosis and some patients with COPD, particularly older patients. Virtually everything else is treated with bilateral lung transplants.
There are national guidelines on age criteria and we all get together and look at the evidence. We are transplanting patients over the age of 60 now, but we look at frailty, because chronological age is probably not the issue, it’s the frailty and degree of comorbidities that count.
So, there’s reasonable evidence showing that frailty and official ways of assessing frailty can predict five-year survival and we don’t undertake transplantation in anybody who doesn’t look like they would have a five-year potential for survival.
Most patients would be under the age of 60, but we are taking patients over the age of 60 and they’re highly selected. That goes for all indications and because of the interaction, particularly with the kidney.
We don’t take patients who have pre-existing renal disease that can’t be sorted pre-transplant. We don’t want to have to do a follow-up kidney transplant in our patients. There’s a chronic shortage of organs anyway for patients with primary renal disease requiring kidney transplant so we don’t want to increase the pool of potential recipients through poorly selected patients.
Around 93% of patients will have an episode of rejection, and acute lung rejections are much more common in the first six months. After six months, you very rarely see any evidence of acute rejection.
We can control the acute cellular rejection very well with immunosuppression and, clearly, if you stop the immunosuppression, then we would see acute episodes. And, indeed, this is one of the hallmarks of a lack of adherence.
As in most diseases, there’s a group of treatment-resistant patients who don’t like to take their treatment or forget. But there are big consequences for the lung transplant population if they do that.
Acute rejection is principally a T-cell process and involves the lung parenchyma and the perivascular structures within the lung parenchyma and the small airways. Acute rejection still occurs, but it’s controlled by the calcineurin inhibitors cyclosporine and tacrolimus.
Patients are always on triple therapy, usually a calcineurin inhibitor, mycophenolate or azathioprine and a small dose of corticosteroids. The mTOR inhibitors sirolimus and everolimus can be introduced because they’re much less nephrotoxic than cyclosporine and tacrolimus. So, in a patient who had no rejection but was developing renal toxicity we’d switch to sirolimus or everolimus.
Around 80% of patients will have hypertension requiring therapy within five years, and 53% of patients develop some form of abnormal renal dysfunction, which is largely related to cyclosporine or tacrolimus therapy, which is one of the principal core pillars of immunosuppression.
Hyperlipidemia is extremely common at 58%, as is diabetes at 40%. And then bronchiolitis obliterans syndrome, which is an airway lung allograft dysfunction complication, seen in nearly 50% of patients by five years.
So, there are challenges for those of us managing these patients in terms of minimising the levels of immunosuppression and individualising the dosage. We’ve moved away from a one-size-fits-all approach so a patient who doesn’t reject very much would be given the immunosuppressive drugs at much, much lower levels than a patient who was regularly rejecting. And we hope with this shift towards a more personalised approach to the post-operative management, we will see decreases in these in these complications as we go on.
But it’s also important to say that around 16 or 17% of our first cohort of patients who could survive 20 years post-transplant did survive 20 years. That’s a remarkable figure, really, when one considers most of these patients would have a life expectancy of 18 months or less at the time of their transplant.
The six-minute walking distance of our 20-year survivors was around 600 metres, which is normal. And, yes, the median creatinine is high, and some patients required renal transplantation between the 15- and the 20-year survival, but we’ve improved our techniques within immunosuppression.
Malignancy is also an increased problem in 20-year survivors, but the majority of these are quite treatable problems such as non-melanoma skin malignancies, and a lymphoma-like programme due to Epstein Barr Virus or post-transplant lymphoproliferative disease, which is also completely curable.
And indeed, the therapy to treat post-transplant lymphoproliferative disease is rather more gentle than one sees in a standard lymphoma or Hodgkin’s patient.
As I mentioned, virtually all patients will have an episode of rejection and, certainly, the chronic long-term problem of bronchiolitis obliterans syndrome (BOS) – or chronic lung allograft dysfunction (CLAD) – is directly related to the number of acute episodes of rejection.
A fibrinoid cellular inflammatory plug blocking the airway is the hallmark histology of CLAD, principally related to episodes of acute rejection. Our understanding of the absolute mechanisms of this fibrosis-accelerated disease are not fully known, but we do recognise the development of airflow obstruction. And, obviously, the more airways that are affected like this, a progressive worsening of the airflow obstruction takes place.
There’s a subgroup of patients who early on when they’re developing these lesions develop a response to the macrolide antibiotic azithromycin. I’ll mention macrolide antibiotics and increasing immunosuppressive drug toxicity later, but azithromycin, interestingly, has anti-inflammatory properties, particularly against neutrophilic infiltration. But this is only in a minority of patients – maybe up to 20% of patients – so, for the 80%, there is still no curative treatment for BOS and it unfortunately, remains the Achilles heel of lung transplantation.
We have shown some improvements, but these are pretty small, and we’d certainly like to see a bigger difference. And really, we’ve made no impact in the last the last 15 years or so. There’s a lot still to do, I’m afraid, if we’re going to get survival from lung transplants up to what we expect to see in liver and kidney transplants, for example.
We have, in recent years, noticed a second form of CLAD called restrictive allograft syndrome, it’s a lot worse than BOS. It’s associated not just with the airway obstruction, but evidence of scarring within the lung parenchyma. And, again, our understanding of the mechanisms, despite intense research, is so far proving quite elusive.
If we look at the adult lung transplant causes of death, number one remains BOS, or graft failure due to obliterative bronchiolitis and restrictive allograft syndrome. But the second most important issue is non-cytomegalovirus infection.
Infection is a big issue and prompt treatment is imperative as these patients get sick very quickly. There’s no such thing as a non-serious infection in these patients because their immune systems are so damped. Any sign of infection requires instant action, no delays.
And certainly, all transplant patients if they ring up looking for an appointment should get an urgent appointment and not have to wait two or three weeks for an appointment. It’s all very well me saying that, of course, but the reality is these patients can go from apparently well to near death’s door in a matter of days if they have a significant pulmonary infection, for example.
If a patient – and it doesn’t matter what transplant they’ve had – comes in and you think they have an infection, do not prescribe macrolide antibiotics. Macrolide antibiotics interact with calcineurin inhibitors in a very, very positive way, causing huge elevations in the toxicity of the immunosuppressive drugs. Many cases of acute renal failure are precipitated by that event.
So, even though azithromycin is rather different and doesn’t have the same characteristics as clarithromycin or erythromycin as I mentioned earlier, whatever you do, do not prescribe macrolide antibiotics. Penicillins and drugs like ciprofloxacin, for sure, they’re fine. But no macrolides, please.
So the first message is: if a patient appears to have an infection, you need to treat early. And secondly, every transplant centre will welcome and give advice. We want to know when our patients aren’t well. What we don’t want to find is two weeks down the line of patients being treated, deteriorating and then having to be transferred to the transplant centre for further therapy.
Speak early, treat early, react early and give early appointments if patients are sick. I cannot emphasise how quickly an apparently well patient following a transplant can deteriorate.
A big problem is that we just don’t transplant enough patients due to a lack of usable donor lungs. Data of a cohort of UK patients waiting three years on the transplant list shows that although 69% had actually been transplanted, 23% of patients had died, four patients had to be removed from the waiting list because they had become too sick and there were only five patients still waiting. So, we really do need to improve the number of donor organs if we’re going to satisfy the need.
The lung is very vulnerable in a potential donor. Often, the kidneys, the liver and the heart can be used, but because most patients are on a ventilator, infections and injury to the lung are prominent. So, in multi-organ donors, the lung is the least used organ, but we can take a damaged lung now and repair it using ex vivo lung perfusion (EVLP) and that’s a very exciting prospect.
So, lungs that are not deemed suitable for implantation into patients are taken from the donor, we bring them back to our lab ventilated and perfused and we repair those lungs. They couldn’t have been used before for transplant, but they’re now suitable for transplantation. It’s a bit Frankensteinian, maybe, but it works beautifully.
And we can do all sorts of clever things with EVLP in terms of treating infections, reducing inflammation, and, in the future, we may well be changing those lungs so that they become less recognised as foreign by the recipient, thus may be obviating the need for anti-rejection therapy. And this is a real time thing; most transplant centres are now doing this.
Our first patient in Newcastle was dying from cystic fibrosis and he would never have had this transplant if we hadn’t repaired those lungs on the EVLP. It’s a very promising technique to improve the numbers of lung transplants.
Every talk on transplantation now includes a question or a discussion on xenotransplantation and this is also being done quite a lot now. The pig lung would be suitable for lung transplants, and we’ve now managed to humanise, if you like, the endothelium of organs so the heart and kidney, particularly, with lung coming along. There have been, as you know, two heart xenotransplants with recipients surviving something like six months – still with some problems, but things are working really pretty well down that route. There was a time when I thought xenotransplantation would never deliver. I’m not so sure now.
18th May 2023
Organ shortage is a major survival issue worldwide and a disproportionate supply and demand was worsened by the pandemic, resulting in a significant decline in global transplant numbers. Here, Chloë Ballesté Delpierre, associate professor, University of Barcelona Medical School, details how countries need to learn from each other’s best practices and work towards a common goal to resolve this ongoing issue.
Organ transplantation is a life-saving procedure for many patients suffering from organ failure. However, the demand for organs far outweighs the supply, leaving many patients on waiting lists for years. The disparity between supply and demand was only worsened by the pandemic, the impact of which has resulted in a significant decline in global transplant numbers. In Europe, the scarcity of donor organs is a persistent issue that has yet to be fully resolved.
Organisations such as the World Health Organization, the European Union Commission and the Council of Europe have all made efforts to increase organ donation rates. However, despite several isolated actions, there has been very little improvement overall. Approximately 30,000 organs are transplanted in the EU annually, far below the estimated 150,000 patients on the waiting list.
While living donations can be a life-saving option for patients, they pose several ethical concerns. The pressure to donate from family and friends can be overwhelming, and the possibility of coercion or exploitation cannot be ignored. It is essential to ensure that donors are not put at risk while in pursuit of helping patients. Therefore, it is important to develop robust deceased donation programmes.
Most transplanted organs in the EU are from deceased organ donors, but these are still in short supply in many countries. Due to the lack of homogenised practices, organ donation rates vary from country to country. Each country also has its own legal and cultural framework, resulting in different consent systems, procurement procedures and allocation criteria.
Efficient donation programmes should be identified and promoted, with the nomination of a national competent authority and professionalisation within hospitals. Doctors from ICU, anaesthesia, emergency and any other departments caring for patients with severe neurological conditions should be duly trained and given the responsibility to lead the organ (and tissue) donation programme in their hospital. Focusing on the clinical activity and ensuring a regulatory framework would avoid fragmentation and unequal access to transplantation for patients.
To address these issues, the EU Commission launched an ‘Action Plan on Organ Donation and Transplantation’ to improve organ donation and transplantation in Europe. Between 2009 and 2015, the total number of transplants increased by 17% and the total number of deceased organ donors increased by 12%. But Covid-19 took a toll on the transplant community, and it is still trying to recover. There are new calls for an updated action plan considering the pandemic’s impact.
Despite the challenges, some countries have significantly increased their donation rates. Spain has one of the highest donation rates in the world, with 40.8 deceased donors per million population (pmp) in 2021 compared with the global average of 6.4 pmp. This is due to a combination of factors, including a well-structured donation system and a strong commitment from healthcare professionals.
To improve organ donation rates across Europe, countries need to learn from each other’s best practices and work towards a common goal, and the European Society of Organ Transplantation (ESOT) Congress helps make this possible. These meetings provide a unique opportunity for the transplant community to come together to share their knowledge and promote progress towards a better future for organ transplantation.
As an elected member of the ESOT Council and a member of the Scientific Programme Committee for the ESOT Congress 2023 in September, I am honoured to be involved in crafting a state-of-the-art programme, which will ultimately improve outcomes for patients with terminal organ disease and increase equitable access to organ transplantation.
18th October 2022
A patient’s transplantation journey does not, however, end in the operating room. Transplant recipients will need to learn to live with a new condition that requires life-long medication and constant monitoring and has many potential complications and risks. This new situation has implications for day-to-day life and can also be challenging from an emotional point of view. Patients may feel overwhelmed and experience multiple contrasting emotions, from relief and joy to anxiety and fear, or a combination of all.
Just as the organ is vital for transplantation, it is also vital to equip each and every transplant patient with the knowledge and tools they need for a positive transplant journey. Over 20 years of first-hand experience as a lung transplant patient has offered me a well-rounded perspective on the importance of patient engagement throughout the journey and I would like to provide some thoughts on why strengthening the relationship between the patient and the healthcare professional is so crucial in enhancing the transplant patient experience.
Communication is key for empowering patients, and it is therefore essential that healthcare professionals create an environment with their patients that is conducive to a meaningful dialogue throughout the entire transplantation journey. Patients who are well-informed are more likely to be engaged and motivated which, in turn, can improve self-management, long-term health and quality of life. The more informed a patient is, the more empowered they will feel to make fully informed decisions about their personal care. This includes information on treatment options, side effects of drugs, possible complications as well as impacts on lifestyles and mental wellbeing. As the management of transplant patients has practical repercussions on day-to-day life it is important that families and carers are also involved.
In the modern world, patients have immediate access to an abundance of health-related information on the internet. This is beneficial in one sense, offering patients a variety of content which can be used to gain a greater understanding of their condition. However, the internet can be a double-edged sword and result in negative effects too. For example, information may be inaccurate or contain facts and statistics which may be daunting to the patient and, ultimately, contribute to anxiety and fear. Therefore, healthcare professionals must now shift and adjust with our modern reliance on the internet. With the guidance from healthcare professionals ensuring patients are directed to sources that provide high-quality, reliable, easy to understand information, including from patient associations and networks, the internet can help enhance the transplant journey. However, it is important this does not act as a replacement for face-to-face dialogue.
Facilitating communication opportunities not only benefits the patient but provides both short and long-term benefits for the healthcare professional, too. Increased dialogue, conversation and transparency with a patient will help the healthcare professional to develop a well-rounded understanding of each individual case, enhancing their ability to provide tailored and personalised care. Combined with increased patient knowledge, this will maximise empowerment and allow effective shared decision making, or “realistic medicine”, along the transplantation journey.
As a transplant patient, I feel I can offer a unique perspective of the importance of empowerment along the transplant process. The future of transplantation is exciting, and I am pleased to see that the value of patient knowledge and experience is being increasingly recognised in the field. I am delighted to have been nominated as Honorary Co-Chair of the upcoming ESOT Congress in 2023 and I am looking forward to working as a patient representative alongside the Scientific Programme Committee in shaping a programme that maximises patient input and perspectives.
Aligning closely with ESOT’s Patient Inclusion Initiative, this congress will welcome valuable contributions from transplant professionals, patient organisation representatives and individual patients. I am proud of the progress that has been made since the very first meeting with patient representatives at the ESOT Congress in 2019, but I know there is still a long way to go and so much more we can achieve.
Healthcare professionals should always remember that through empowering their own patients, they are also empowering themselves. Strategies that promote patient engagement help to achieve the best possible care, support and outcomes for patients which ensures not only that patients have a life post-transplant, but a life of quality, enjoyment and fulfilment. In the future, I hope that patient empowerment will truly be at the heart of organ transplantation.
25th October 2021
Kidney transplant patients with prostate cancer still achieve the same benefits in terms of overall survival as those without the cancer, according to the results of a retrospective analysis by researchers from the Division of Nephrology, University Hospitals, Ohio, US. End stage kidney disease (ESKD) which requires maintenance with dialysis or a kidney transplant for survival is associated with an increased risk of death. For example, one retrospective analysis of 242 patients with ESKD, observed an annual mortality rate of 7.4%. Nevertheless, other data has found that the mortality risk from ESKD has actually decreased over the last 15 years although some work indicates how ESKD have higher levels of prostate cancer.
Kidney transplant patients have an improved quality of life compared to those continuing with dialysis but there is uncertainty over whether or not the presence of prostate cancer impacts on mortality risk in those either with ESKD or after transplantation. These were the questions to which the Ohio researchers sought answers in the present study. They turned to the US renal data system and included men aged 40 to 79 years of age with ESKD and took the main exposure to be incident prostate cancer which developed after the initiation of dialysis but before a kidney transplant. Since the clinical characteristics of patients with ESKD and prostate cancer might differ to those without prostate cancer, the researchers used propensity matching with a control group of ESKD patients but without prostate cancer and set the outcomes of interest as the time to kidney transplant and death.
Findings
There were 15,554 patients with ESKD and prostate cancer who were matched with controls, the majority of whom (47%) were aged 70 to 79 years with 42% aged 55 to 69 years. Within the matched cohort, 77.6% of patients with prostate cancer died compared to 77.1% of control patients during a mean follow-up of 3.1 years for those with prostate cancer and 3.5 years for controls. The presence of prostate cancer was associated with a 22% lower likelihood of having a kidney transplant (Hazard ratio, HR = 0.78, 95% CI 0.72 – 0.85) and an 11% higher mortality risk (HR = 1.11, 95% CI 1.08 – 1.14) compared to controls.
However when considering kidney transplant patients and using patients without a prostate cancer and no transplant as the reference point, the hazard ratios for the time to death were 0.20 (95% CI 0.18 – 0.21) for transplant patients with prostate cancer and also 0.20 for transplant patients without prostate cancer.
The authors concluded that the presence of prostate cancer in those with ESDK was associated with only a modest increased risk of death but that once these patients had a kidney transplant, the survival benefits were identical to those without cancer. The suggested the these findings indicate that in kidney transplant patients, the presence of prostate cancer should be a barrier to provision of a new kidney.
Citation
Sarabu N et al. Prostate Cancer, Kidney Transplant Wait Time, and Mortality in Maintenance Dialysis Patients: A Cohort Study Using Linked United States Renal Data System Data. Kidney Medicine 2021
29th July 2021
Among immunocompromised individuals such as kidney transplant patients, a single COVID-19 vaccine dose has been found to elicit a sufficient response in only 17% of individuals. Furthermore, after a second dose, the response only increased to 54%. With evidence of a lower immune response to vaccination, the French National Authority for Health issued a recommendation in April 2021, that immunosuppressed, recent bone marrow transplant, those on dialysis, and patients with autoimmune diseases who did not respond after two doses of a COVID-19 vaccine, should be offered a third dose.
Given the evidence that even among kidney transplant patients who are fully vaccinated, severe COVID-19 can develop, a team from the Department of Nephrology and Transplantation, Strasbourg University Hospital, France, set out to assess the response to a third vaccination among kidney transplant patients who had an inadequate response to a second vaccination dose. The team examined the effect of the mRNA-1273 (Moderna) vaccine and included all kidney transplant patients who had no prior history of infection with COVID-19 and had anti-spike IgG antibody levels less than 50 arbitrary units, one month after administration of the second vaccination dose. They set a minimum antibody titre level of 50 units, so that any responses above this level could be considered as positive.
Findings
A total of 159 kidney transplant recipients with a median age of 57.6 years (61.6% male) and a median time from transplantation of 5.3 years were included in the analysis. After the second dose of vaccine, 59.7% (95) of patients had not generated an antibody response and the remaining patients showed a response below the positivity limit (6.8–49.9 units). The third vaccine dose was administered a median of 51 days after the second dose and the antibody response was then measured approximately 28 days after this third injection. However, at this time-point, only 49% of patients had antibody levels above 50 units. In addition, a response to the third vaccination was much more likely among those who had developed a response to the second dose (81.3% vs 27.4%, p = 0.01, second dose responders vs non-responders). The results also showed how kidney transplant patients prescribed a combination of tacrolimus, mycophenolate and steroids, were much less likely develop a response than those treated with other regimes (35% vs 63%, p = 0.006). No other factors such as sex, years since transplantation, or serum creatinine levels, had an effect on the development of an antibody response.
The authors reported on how despite three vaccination doses, 51% of kidney transplant patients failed to generate a positive antibody response and that this was more likely among those prescribed a triple therapy regime and concluded that kidney transplant patients should be offered a third vaccination dose.
Citation
Benotmane I et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients with Minimal Serologic Response to 2 Doses. JAMA 2021
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