Ear Replantation

Posted by Peter Morris on April 16, 2014

In the images section of this weeks New Eng. J Med 2014;370:1541 there are 4 remarkable pictures. In the first is the site of the ear amputation, bitten off by a pit bull dog. in a 19 year old woman, while the second picture shows the retrieved ear after debriding. The arterial blood supply was restored using a branch of the posterior auricular artery. As no suitable veins were available leeches were applied to provide venous drainage for 17 days and the third picture shows a leech in action. The ear remained viable and the 4th picture shows a healthy looking ear at 24 days. At 4 months the ear was stable and a normal appearance was maintained. Truly remarkable!

Renal denervation for resistant hypertension

Posted by Peter Morris on April 11, 2014

There has been very considerable enthusiasm for renal denervation for resistant hypertension in the last few years. However it is not a new idea and I well remember as a young surgeon in the late 60’s carrying out open renal denervation for hypertension under the direction of the renowned nephrologist, Professor Priscilla Kincaid-Smith. However anecdotally there did not appear to be any benefit from this procedure. The development of renal denervation using radiofrequency ablation is a newer minimally invasive approach and early studies suggested that this did produce an improvement in resistant systolic blood pressure. However in the latest edition of the NEJM Bhatt and colleagues (N Eng J Med 2014; 370: 1393-401) report the findings of a very good trial which fails to show any significant improvement in blood pressure. This is accompanied by an excellent editorial on the subject by Messerli and Bangalore (N Eng J Med 2014; 370: 1454-57).


In this excellent trial, which was a prospective, single blind, randomised, sham controlled trial, patients with severe resistant hypertension were randomly assigned in a two to one ratio to undergo renal artery denervation with the Symplicity catheter or a sham procedure (a renal angiogram). This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension at 6 months, compared to the sham control patients. This is a model study and as the authors conclude “renal denervation in the current trial appeared to be safe with no unanticipated side effects, however a significant effect on systolic blood pressure was not observed, further evaluation in rigorously designed clinical trials will be necessary to validate alternative methods of renal denervation or to confirm previously recorded benefits of renal denervation in patients with resistant hypertension.”

It is also relevant that when we transplant a kidney we are transplanting a denervated kidney and in fact in the pioneer days of kidney transplantation there was considerable concern as to whether a denervated kidney could function appropriately. However patients with a transplanted kidney still had problems with elevated blood pressure even if their own kidneys had been removed.

Donor specific HLA alloantibodies (DSA) in liver transplantation

Posted by Peter Morris on April 8, 2014

A conference was held with an invited faculty (predominantly from the USA) and sponsored by industry to discuss the impact of DSA in liver transplantation and this article reports their opinions.

It was agreed that the presence of DSA are recognised now to have a deleterious effect on outcome, particularly if HLA Class II antibodies, just as was the case for ABO incompatible liver transplants.. These deleterious effects include not only antibody mediated rejection but also bile duct strictures, vanishing bile duct syndrome, plasma cell hepatitis and accelerated fibrosis. The authors feel that there needs to be standardised testing for DSA as well as diagnostic criteria for both acute and chronic AMR. Just as in renal transplantation IgG DSA are likely to be more important than IgM but this still remains unknown.

Overall this is a relatively good summary of current opinion, even if rather parochial. Indeed many key references are not cited. But it is opinion and therefore of limited value as evidence and I would like to see a good systematic review on this topic.

Transplant Trial Watch April 2014

Posted by Simon Knight on April 2, 2014

The Transplant Trial Watch for April 2014 is now available on the CET website and via our app for iPhone, iPad and Android. We have selected 10 RCTs reported in the past month and looked at their quality and impact.

This month, trials include ATG vs IL2RAs in kidney transplantation, long-term outcomes from CNI withdrawal and tacrolimus-sparing using sirolimus in liver transplantation.

Tacrolimus maintenance doses

Posted by Peter Morris on March 27, 2014

The Collaborative Transplant Study ( CTS ) first newsletter for 2014 (February 1 – available to CTS participants only) presents a particularly important analysis of outcomes of deceased donor kidneys between 2003 and 2012 based on the tacrolimus trough levels one year after transplantation. If the maintenance trough levels were less than 5ng/mL there was a significantly worse graft survival at 5 years compared to those with trough levels ranging from 5 to greater than 10 ng/mL. As most patients were receiving MPA as well, CTS have looked at low dose MPA versus full dose MPA and interestingly patients who received a full dose of MPA did not show that much difference in graft survival, even with a tacrolimus trough level at one year being  less than 5 ng/mL. However if they were receiving a low dose of MPA results were significantly worse.

This is reminiscent of the studies from Australia many years ago comparing different doses of azathioprine with low dose steroids where inferior graft outcomes were achieved if the dose of azathioprine was less than 2mg/kg. Thus maintenance immunosuppression must be adequate to ensure long term graft survival. In time we may be able to identify with various biomarkers which patients are at risk with inadequate immunosuppression.

World Kidney Day

Posted by Peter Morris on March 14, 2014

The World Kidney Day for 2014 is to be March 13th and it is featuring chronic kidney disease and ageing. They make the point that although chronic kidney disease can occur at any age it becomes more common with increasing age, and indeed after the age of 40 kidney filtration begins to fall by approximately 1% per year. Any damage on top of the natural aging of kidneys due to diabetes, hypertension and so forth of course only hastens the decline in renal function. On World Kidney Day everybody is encouraged to have a glass of water on arising at the beginning of the day to remind them of the importance of water and kidneys. However it should be pointed out that although water may protect your kidneys, there is no scientific evidence behind this idea. But it will certainly help everyone to remember that you need to take care of your kidneys.

Neil Russell appointed at Cambridge

Posted by Peter Morris on March 6, 2014

Neil Russell, who was one of the two first Research Fellows at the CET, has finished his surgical training at Addenbrooke’s Hospital in Cambridge and has just been appointed as a consultant abdominal transplant surgeon there. We were all delighted to hear the news. He is the first CET Research Fellow to reach consultant status. He successfully completed his MCh thesis at the CET, directed at Cyclosporine sparing in renal transplantation.

March 2014 Transplant Trial Watch now available

Posted by Simon Knight on March 3, 2014

The March 2014 edition of the Transplant Trial Watch is now available online and via the CET’s app for iPhone, iPad and Android.

This month, trials include the effects of cyclosporin A and tacrolimus on fibrosis following liver transplantation for hepatitis C, intravesical vs. extravesical ureteroneocystostomy in renal transplantation and the use of sitagliptin in new-onset diabetes after renal transplantation.

Origins of Evidence Based Medicine

Posted by Peter Morris on February 21, 2014

There was an interesting editorial by Richard Smith and Drummond Rennie in the BMJ recently. The editorial is based on two interviews of pioneers in this field by Richard Smith, the former editor of the BMJ. In the first oral history he interviews Iain Chalmers, Muir Gray and David Sackett. They said that authors from a previous generation were inspirational, namely Thomas C Chalmers, Alvan Feinstein and Archibald Cochrane. David Sackett tells us that he read Chalmers’ 1955 report of a randomised factorial trial of bed rest and diet for hepatitis and said:

“Reading this paper not only changed my treatment plan for my patient, it forever changed my attitude towards conventional wisdom, uncovered by latent iconoclasm and inaugurated my career and what I later labelled clinical epidemiology”

Iain Chalmers, cofounder of the Cochrane Collaboration, tells us that he was working in Gaza as a GP and realised he did not have the evidence to help him treat his patients and that is what stimulated him to go down the path that he eventually did. David Sackett, perhaps regarded by many as the father of evidence based medicine, came to Oxford from McMaster as Director of the newly established Centre for Evidence in Medicine, having been recruited by Iain Chalmers and Muir Gray. He had a rough time in Oxford at the start, particularly when he criticised data in the Oxford Textbook of Medicine for being wildly out of date for not citing relevant randomised trials. However gradually he converted everyone to the concept of practicing medicine on as good evidence as one could obtain. He did not coin the phrase evidence based medicine, but says that Gordon Guyatt, Professor of Epidemiology, Biostatistics and Medicine at McMaster University, after he took over as Director of the Internal Medicine Residency Programme in 1999 , at first suggested  Scientific medicine as the appropriate term for this new discipline but this also created antagonism and he changed it to evidence based medicine.

There is a second interview by Richard smith, hosted by JAMA in which he interviews Gordon Guyatt, Drummond Rennie, Brian Haynes, Paul Glasziou and Kay Dickersin, all pioneers in the development of evidence based medicine. This is quite a long interview, the best part of 50 minutes but well worth the time. Some interesting points struck me, namely that Brian Haynes felt that everyone should try to provide the best evidence, but Kay Dickersin commented that because of the push from “the academic reward system” there was a lot of junk published and this makes it so much more difficult to obtain relevant evidence. She also made the point that observational studies and their appraisal needs more attention and there is a need for much more attention on safety of interventions. Doug Rennie was adamant that money had to be taken out of the system and he enlarges on that in the interview. Paul Glasziou in looking to the future made two points, firstly that systematic reviews are done too slowly, taking at least two years to complete in the Cochrane organisation for example, and one needed a system that could produce a systematic review within two weeks. The second point he made was that the bulk of the work was directed at pharmacointerventions and there needs to be much more study of nonpharmacological interventions.  Guyatt felt that there has to be much more of pre-processed information available and I must say that the Transplant Library fits in exactly to what he would like to see develop in the future.

The editorial gives you the main thrust of the interviews but for people who are generally interested in the origins of evidence based medicine and where it might go in the future these videos are required watching. Richard Smith in summary feels that there is still a long way to go. I would recommend watching these splendid interviews.

Evidence in Transplantation (EVIT course): Last few places

Posted by Liset Pengel on February 13, 2014

The deadline to register for the Evidence in Transplantation (EVIT) course has been extended and you can now apply for one of the last few places of this highly rated course. EVIT last call

The EVIT course is organised in collaboration with ESOT and will run on 21 and 22 March 2014 at the Royal College of Surgeons, London, UK.   The two-day course  is aimed at professionals from all disciplines actively involved in organ and tissue transplantation who want to increase their skills in evidence-based decision-making.

All lectures and small group sessions will use examples from the area of transplantation. The participants will learn how the validity and applicability of research evidence can be appraised and will carry out part of a systematic review.

To apply, visit the ESOT website.

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