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Ok, perfect. Er, good evening everyone. Um My name is Mars, I'm a cardiology and intensive care doctor working in London. Um and I'm also a vice president of British Transplant Physician trainees Society and welcome tonight to our first of our um educational series just to give you a bit of background. So BTP T is a group of um UK physician trainees which are all passionate about solid organ transplantation across a range of medical specialties. We're basically trying to catch up with our surgical colleagues in the her society who've beat us about 20 years in the formation of their society. But in the last year, we made really rapid progress. We've gained representation on a number of organ advisory groups in NHS blood and transplant. Um We've also gained affiliation with the British Transplant Society at the Congress um just this month. Um and our membership is open to any physician trainees or post physicians and within three years of their t for more background and our vision very much is to provide education, training, mentorship, facilitate trainee driven research, um represent physician trainees and build relationships between them physician and surgical trainees. And indeed, um our BTP T elections have just opened. So do visit our website um on BTP t.co.uk if you are interested and want to get involved and you can see what else is going on. So, moving on to tonight, we've got our first of our educational series and we're hosting it on this great app called Medal, which hopefully some of you have already used before you can follow us on here um to learn about any future um educational events. And we're aiming this very much at doctors from all specialties who are interested in transplantation. Um And tonight, we've got medical students, foundation trainees, core trainees, registrars from the UK and abroad. Um What we're hoping is to provide education content, which is really engaging for inviting speakers from across the UK to share by inspire trainees and help us develop our careers as future transport physicians. And we'll aim to do these every month initially, starting off quite broad and then we'll develop more specialist content as we go on and it'll all be recorded and available for viewing. So tonight's er event is on transplants on the acute take and we've got two fantastic speakers. Er and we're aiming to give you a broad overview of what to do when you see a patient um with a solid organ transplant that arrives at your hospital with a specific focus on um liver and kidney. So I'll be handing over to my colleagues, um Emma and Vroom who will be sharing sessions. Uh, so what we'll do is we'll do both talks and that will be followed by a question and answer time. So, um, do pop your questions in the chat. Um, and then we'll bring those all up towards the end and we'll end to finish, um, at 830. So, um, with that, I'll hand over to Emma. Hello. Thank you. Er, so it's my pleasure to introduce our first speaker. So um Professor Colin Geddes, who is a professor at the University of Glasgow School of Medicine and a consultant nephrologist. He has subspecialty responsibilities for living donor workup and for acute transplant, er acute transplantation. He is the living kidney donor network, co-chair and a member of the Scottish Donation and Transplant Group. So I'll hand it over to prof thank you very much for the invite. Can I just confirm that you can hear me and that you can see my slides? Yes, all looks good. Great. So, well, the task that you thanks very much for the invite and the task that you gave me of five tips for assessing a kidney transplant patient and acute take. Um Really got me thinking and I realized that in my first two or three years of doing medical receiving, uh I never saw a patient with a kidney transplant because 25 to 30 years ago, they just weren't nearly so prevalent. The first kidney transplant in the world was in 1954 in Boston between two identical twins who are seated at the front here following the operation. And then it was performed by the surgeon Joseph Murray on top left. Um here and you can see that they're both looking pretty healthy uh afterwards. Um Things moved fairly slowly. After that. The first kidney transplant in the UK was in Edinburgh in 1960 performed by this gentleman, Sir Michael Woodruff. And again, it was on identical twins and here's them after not really following the lifestyle advice that we give after a, after a kidney transplant. But of course, the vast majority of people with endstage renal failure don't have an identical twin to donate them a kidney. And er, the problem is everyone else, er, needs to take immunosuppression to avoid acute rejection, which will happen inevitably if you don't have immunosuppression and the immunosuppression agents took a long time to develop because of, of a whole variety of problems, some of which we'll cover this evening. Um And the majority of kidney transplants are done by de from deceased donors, maybe about a third in the UK are from living donors and setting up a deceased donor. Uh kidney transplant program is, is no minor undertaking. So by the time I was qualified and practicing there still weren't that many people with functioning kidney transplants around, but the numbers have gone up and up over the last few years and these are data from the UK renal registry, which show prevalent patients on kidney replacement therapy in the UK. And you can see that there are over 70 nearly 70,000 people er on kidney replacement therapy. The majority of them now are uh patients with a functioning kidney transplant. And there are more than 30,000 pa patients with a kidney transplant around. And that means that no matter what branch of adult medicine you go into, you will come across patients with a kidney transplant including on the acute take. So the typical patient, the kidney transplant patient you might see in the acute take is gonna be likely gonna be middle aged or, or uh e elderly. You can see here's the prevalent transplant patients in the UK and the majority of the of them are in the sort of 50 to 70 age group. Although there's a tail on either side, they're gonna have comorbidity that relates to whatever it was that caused their kidneys to fail in the first place. And these are data again from um a renal registry. This time, the Scottish renal registry showing over time, uh the uh the proportions of patients with different primary uh renal diseases groups together. So we've got diabetes and gray familial and hereditary nephropathies like Alport syndrome and blue glomerular diseases such as IGA nephropathy and blue hypertension or renovascular disease. Uh in a in a pale lilac, various miscellaneous ones in purple, other systemic diseases that affect the kidney and greens, for example, uh systemic lupus erythematosus and then tubal interstitial disease, mainly autosomal dominant polycystic kidney disease and reflux nephropathy in, in the red. And what you can see is that the proportion of patients with diabetes as a primary renal disease is increasing. So, these are people who've had diabetes for a long time. And so you can see that there'll be quite a number of things that the comorbidity that, that these patients have, that have accumulated uh over the years. Um Right, there we go. Um So uh the other thing is that they'll have comorbidity that relates to having chronic kidney disease. And er chronic kidney disease is an independent risk factor for cardiovascular disease or heart failure, atherosclerotic disease, but for vascular disease, stroke, et cetera. And you can see on this graph here that as the, as the G fr falls, then uh the uh cardiovascular mortality and all cause mortality go up as well as uh associated morbidities. And all of these patients will have been through uh progressive decline in kidney function before they get their kidney transplant. And then there's going to be morbidity that relates to the transplant anatomy. So, unlike liver, heart lungs, er the kidney transplant is not placed, uh it does not replace uh one of the native kidneys, the native kidneys are left in place and the transplant kidney is implanted in extraperitoneally in the left or right iliac fossa with anastomosis to the iliac vessels. Uh and what that means is that because of the vascular anatomy, there may be a pressure effect, uh or a steel effect of the arterial circulation going down to the leg. And there may also be a pressure effect on the venous return. And so these patients are at increased risk of deep vein thrombosis ischemia in the leg, er, as a result of the transplant and as a result of the abnormal plumbing, er, with a, a reflux of, of urine up the ureter. These patients are more at risk of a urine infection as well and we mustn't forget that because the kidneys are still in place. They can cause trouble as well and they can get infections, they can get er, stones and they can get er tumors and they're gonna have morbidity related to being on immunosuppression. So all of these patients will be on long term immunosuppression. And here you can see that the cause of death in patients with kidney transplants compared to patients on er dialysis. And you can see that infection dominates as a cause of death in transplant er patients. And it's highlighted again here where we're seeing the same groups over time, the er blue line is malignancy, the black line is infection and you can see that they tend to dominate but look what happens during the COVID pandemic showing just how vulnerable these patients were to COVID uh related mortality. So, all, as I say, all of the patients will be on immunosuppression and the immunosuppression protocols that they're on will are variable. There is no er, defined perfect er immunosuppression protocol and different units in the UK, use different protocols but the principles are the same. There's induction at the time of uh the transplant which is high dose steroid and either polyclonal or monoclonal antibodies followed immediately by maintenance therapy with most commonly tacrolimus, mycophenolate and prednisoLONE. Although increasingly a lot of patients have been managed without long term uh prednisoLONE. Um, and because of the induction, er, they, they get the 1st 3 to 6 months are the highest risk for infections. These patients will also in selected cases be on antibiotic, pro prophylaxis, antimicrobial prophylaxis, uh cotoxic isole to prevent Pneumocystis, valGANciclovir to prevent CMV. Infection is aid and pyridoxine to prevent TB, as I say in selected cases and usually for a defined period of 3 to 6 months. So what will they present to the acute to take with patients with kidney transplants? Well, just the typical medical complaints that you'll all be used to for those of you who do medical receiving regularly. So it's chest pain, it's shortness of breath, it's off the legs, um, weakness, er, vomiting and diarrhea, et cetera. And the approach really is, is as standard, but there's a few things to look out for. There's things to look out for relating to their immunosuppression and there's things to look out for the kidney transplant specific. So let's take a typical patient uh presenting med to the medical, take 64 year old female who's got end stage renal disease, secondary to do to autosomal dominant polycystic kidney disease. And she had her first kidney transplant three years ago and presents with four days of shortness of breath. So your initial re approach is gonna be the same as any other patient on the acute, take ABCD E then a history um including looking back through any electronic records that might be available to get more information. Uh examination, routine blood test, not surprisingly, uh you want to know what the U are looking like. Uh but other routine tests there, ECG chest X ray and then depending on what you're finding so far, you may want to go on and check ad dimer lactate, venous blood gas, arterial blood gas, et cetera. The diagnosis that you should think about. Well, um I'm sure you're already thinking, could this be infection? Could this be fluid overload? Cardiac failure? Could it be pulmonary thrombo embolism just as you would be in any other patient presenting to uh the the acute take? But my tip number one is remember to think of opportunistic infections. Now, no Alistair is going to go on and talk a little in a lot more detail about infections in patients who are immunosuppressed. So I'm not going to dwell on this, this chest X ray shows uh uh what would be consistent with uh pneumonitis and people who get, have kidney transplants, get the same infections that you or I could get. So this could easily be COVID. Um But it's worth thinking about Pneumocystis, uh cyto medic megalovirus and TB as opportunistic infections. And I suspect Alisa will cover this as well, but I don't, I think it, it bears repetition. Um send a blood sample for A CMV PCR in any transplant patients with symptoms of infection where the, there isn't an obvious non viral cause. Tip number two is that their kidney function is unlikely to be normal. They only have one kidney. It's remarkable that some uh kidneys er, give a, give AAA creatinine of less than 100. Er, we've got a transplant patient in Glasgow who's had a kidney for 54 years who has a serum creatinine of 91. But the majority of patients, their kidney function is likely to be um sub subnormal. And what you need to do is try and find out what their baseline kidney function is. Now. Electronic records are good nowadays. So we can usually go back and find out but the patient might well know either because they take a very keen interest in it when they're at the clinics or because many patients in the UK have got access to a system that used to be called patient view, but it is now called patient knows best where they can see their own laboratory results uh and follow them. So they, they may be able to tell you what their baseline is. Um If the patient is unwell and you find that they've got acute kidney injury, the acute kidney injury is unlikely to be due to rejection. It's understandable that people would think that that would be the most likely cause. But in actual fact, most acute rejection in kidney uh transplant patients is asymptomatic and it's much more likely that whatever it is that's made them unwell and present to the acute take is associated with an acute kidney injury rather than that acute kidney injury is due to rejection. Um but the fact that the kidney function is unlikely to be normal is relevant to investigations you might perform. So be careful that the D dimer is likely to be elevated and therefore much less useful. Um And it's likely to be relevant to any treatment that you give and that you need to be careful with drug dosing. But just as you would be with somebody with native kidney disease, tip number three is don't withhold intravenous contrast because of concerns about renal nephrotoxicity. So in this patient, we said earlier that pulmonary thromboembolism would certainly be on the differential. And if other things are pointing towards that as a potential diagnosis, don't withhold contrast because you're worried about renal toxicity. There isn't time in this lecture to go into all the evidence that is available that uh in modern times. Um intravenous contrast is not such a concern. Um And I think too many patients have come to harm from not getting a diagnosis because of not getting adequate imaging. Arterial contrast is more of a concern for acute kidney injury. But when you think about it, um the majority of the situations where one might be giving arterial contrast, particularly uh in association with acute take are gonna be for a life threatening situation such as this left main stem stenosis. And again, you certainly don't want to avoid giving contrast for fear of acute kidney injury and miss the opportunity to save the patient's life. The majority of acute kidney injury associated with in arterial contrast is reversible. Number four would be know a little bit about tacrolimus. Um That's the, the best anti rejection drug we've got, er, we used to use cyclosporin, they actually similar drugs but in the modern era, we, we tend to use tacrolimus but there will be a few patients on tacrolimus. The principles are the same. The first is prescribe it by a brand. You need to be very careful because er, some patients prepare preparations are twice daily and some are once daily. And you, as you can see here, there are a lot of preparations so you need to be very careful that what you're prescribing is the patient's usual brand at the correct dose and the correct frequency. Second thing is it's worth getting a tacrolimus level when somebody's unwell and we're looking for roughly a 12 hour, er, level in somebody who's been on is on a twice daily preparation and a 24 hour level in somebody on a once day, er, daily preparation. So, what to do is you put a request out for measuring measurement of a blood type level the next morning and it needs to be done before the morning dose. Now, the patient will be very used to doing this because that's what they do when they come to the clinic. So if you let them know that that's the plan, I'm going to do a tacrolimus level. Can you delay your morning dose until you've had your blood taken? Most of them will be well used to doing that. Um And then you need to be very careful when prescribing medicines that interfere with the metabolism of tacro tacrolimus. And the two culprits we come across frequently are Clarithromycin, which is often given in people with penicillin, allergy or flu fluconazole and patients on these drugs, their tacrolimus levels can go up very rapidly and cause nephrotoxicity and various other problems if you don't reduce the dose in anticipation of this. So either avoid these drugs or if you're using them, take advice uh and be very careful. And then another useful tip for tacrolimus is that, that some patients come in with vomiting and can't er, er take their immunosuppression, which is a big worry we can give steroids intravenously, giving the others intravenously is challenging. But for tacrolimus, you can open up the capsule if they use capsules and er, drop it in sub sublingually and they can absorb, absorb it. And then tip number five is, if you conclude uh that the diagnosis is fluid overload, then don't skip on diuretic for fear of nephrotoxicity. Of course, this applies to native kidneys as well. Diuretics are not nephrotoxic. When I tell the I MT S er this, they've rotated from various places and I say to them, di diuretics are not nephrotoxic. They give me a look that makes me think that they don't believe me. Um And I can't see any of you on the, on the screen, but I if any of you are skeptical in this, this er document that was produced a couple of years ago in conjunction between the UK Renal Association and the British Society for Heart Failure. Um very clearly uh documents the evidence behind this and why we shouldn't um skimp on diuretic. Uh what you see if, if you get effective diuresis, which of course is what we're aiming to achieve in somebody who is fluid overloaded and needs diuretics. Effective diuresis is associated with a reduction in EGFR, but that is not nephrotoxicity. It's a hemo dynamic effect that we should tolerate and accept. Um And we actually accept up to a 30% fall in eg fr with effective treatment for fluid overload. Um And while we're on the topic, ace inhibitors and A RBS are not nephrotoxic nor is Metformin nor is trimethoprim. However, the reason we stop uh these drugs in acute kidney injuries because ace inhibitors and angiotensin receptor blockers inhibit the ability to autoregulate glomerular filtration rate in the face of reduced effect of plasma volume such as uh diarrhea or hemorrhage. Uh but they're not causing damage to the kidney there. It's simply a hemodynamic effect and it will be reversed when you correct the underlying problem. And the patient can go back on the ace inhibitor or Ab Metformin. We stop it not because it's toxic, but because uh at low levels of kidney function, there's a markedly increased risk of lactic acidosis and trimethoprim increases serum creatinine and reduces eg fr but that is not an effect on glomerular filtration rate. It is not nephrotoxicity. It's due to the er er impaired secret um secretion of creatinine from the renal tubules, which is of no health consequence to the patient. And tip 5.5 have sneaked an extra one in. If you think the diagnosis is fluid overload with pulmonary edema, as shown in this x-ray, then think about transplant renal artery stenosis in the etiology. Now, of course, it's more likely that it's simply fluid overload, salt and water retention, which patients with the low kidney function are prone to uh possibly also combined with reduced cardiac function that may be chronic but may be new. So they may have a new valvular problem. They may have had a myocardial infarction. But further down on the list of possibilities is transplant renal artery stenosis. And here's a patient, an a arteriogram uh in the iliac vessel. And then you can see a branch, not sure if my arrow point shows up. Hopefully it does. Here is a narrowing quite close to the origin of the transplant renal artery. The rest of the artery here feeding the kidney and the physiology of this is interesting because the kidney uh uh um interstitium or the, the the macular dense, I should say it interprets this as a reduced effect of plasma volume. So increases renin production and that that leads to the production of angiotensin two which causes vasoconstriction, s systemic. So, uh increased BP and causes intense salt and water retention by the t of the kidney. So, fluid overload with pulmonary edema. And um that's in an attempt to maintain glomerular filtration rate. But if the stenosis is tight enough, it won't manage to do that. And the glomerular filtration rate will go down. And if you're thinking on your feet, you may put two and two together and think perhaps this patient with pulmonary edema and a hypertension and a kidney transplant has actually got a transplant renal artery stenosis and with a stent, everything will be uh corrected. So it goes without saying that um there's always a happy renal registrar on the phone, um, available for advice about kidney transplant patients. And we tend to expect people to give us a phone just to check. There's, there isn't anything else to be thinking about. But hopefully the tips that I've given you can see you through, uh, the 1st 12 to 24 hours here they are. Uh, again, um, I was thinking this is probably going to be a bit like, uh, I imagine Desert Island Discs would be. Whereas when you, after you've done the program, you think of other ones that you should have put in, but maybe some other topics will creep up in the discussion. Thank you very much. Great. Thank you very much, Professor. Get, it's for a fantastic talk and um getting us off to a great start. Um So I think now we'll move on to um the liver talk. Um And for this, we have Professor o'brien. Um Professor o'brien is a consultant hepatologist at the Royal Free Hospital and a Professor of Experimental Hepatology at UCL. Um He's also the clinical director of the UCL Comprehensive Clinical Trials Unit. Um He was the chief investigator of the Attire trial, which is published in the New England Journal of Medicine and is currently also chief investigator, the aseptic trial. Um both these trials making up the 2nd and 3rd largest trials of decompensated cirrhosis um completed worldwide. And so with that, um I'll hand over to, thanks very much Vikram. Let me get this. Oh, there we go. We don't want to do that, do we? I've already messed it up, haven't I? There you go. Published a New England journal, but can't get this right. Right. Have I got a screen? Yes, it looks good. Great. Thank you very much. So, um I've never given this talk before, so, so, uh thank you. Um, and, and I guess clinically I'm, I'm probably quite well suited in, in that I don't do much transplantation. I II work the people up and then I, I let the youngsters with a lot more attention to detail than perhaps I do at my everincreasing age. Take care of this. So I'm sort of the person perhaps best suited to give this talk. So, so, so yeah, here it goes. And I think one of the things perhaps disappoints me as someone who loves clinical research is that there's not a lot of evidence here. I think it's difficult to do trials in people like this unless you've got a new drug such as the tacrolimus cycloSPORINE study from some years ago because these are precious people, of course and, and antibiotic trials are difficult enough at the best of times. So, so I'm not sure we'll ever see any, any really good trials in this area because it, it is tough. Um So my top tips. So I did a renal job a million years ago at Saint Mary's and worked for someone called David Taub who, who was a tough taskmaster and taught me a lot but did rather scare me and the patients did too. So, so I think the first thing is don't panic. Um You know, this is about infection. You guys see infection day in day out, especially those uh uh of, of you who do a lot of intensive care. This is, this is your bread and butter. Um sample everything I think, you know COVID was, was, was obviously awful, but it did mean that we focus more on viruses. Now, we, we look for viruses now, whereas perhaps before they, they were the sort of forgotten er, er, er, in infection apart from perhaps uh during flu season, do call for help and do prescribe the most appropriate antibiotic. And if you do all of those, you're doing a great job. So please don't panic. Uh These are the sort of infections that you will see. Um now, of course, things can differ and it doesn't always fit these sorts of algorithms that people publish. But by and large, this is pretty much the way it works. So less than one month, you probably won't see these people on an acute take um because they, they, they'll be managed at the transplant centers. But again, bacteria, you know, infection, 80% of patients are going to get infection and 70% of those, it's going to be bacteria. And certainly for the liver, people going into transplantation. Infection is a big, big problem and, and sadly, we coat these people in antibiotics often with very little evidence of infection. And so we have a lot of multi resistant drug organisms. So this is a real challenge. And again, microbio, you may not be able to get them in the middle of the night, but you can certainly discuss things with them the following day. When all the cultures have been sent, often these infections will be bloodstream pneumonia. Uh, of course, the surgical sites, er, for, for any of the surgical trainees, er, er, um intraabdominal infections, urinary tract infections. And don't forget clostridium dia, of course, but also don't forget the viral infections and, and of course, er, are different COVID and then what the first six months or the 1 to 6 months, again, slightly pretty similar. You can get these sort of donor acquired gut colonization organisms, but again, fairly similar, the surgical infections by and large have perhaps got a little better. Um, but again, viruses are, are important and then six months out, especially for the liver patients. A lot of the immunosuppression drugs have dropped by then. And so really, they're more like your standard liver patient or standard person who might have an infection and of course, the difference between these guys and your decompensated patients is by and large, they have pretty normally functioning liver. So it's much more straightforward at that stage. As I said, I make no apologies for putting this in twice. Do not be afraid to ask for help. The people working at the transplant centers fully accept that they're going to receive these calls and they are by and large. Glad to help. As I said, infection is a major cause of mortality and morbidity. About 80% of people will be diagnosed with an infection. 70% of these are going to be bacterial and then fungal and viral, of course, are well documented and it it is the basic principles as, as I said in the top tips do do what you do every day and you'll get it right. So the patients are often coated with empirical and prophylactic antibiotics coming into transplant and postoperatively. So, so again, don't be lazy with the cultures. You will see, sadly, multidrug resistant organisms get the surgeons involved. Wound infections are very common cholangitis and peritonitis, of course, are the donor derived infections. Again, these would be managed largely at the transplant centers and they'll have the information about these things. But pseudomonas is a big problem and MRSA, we see it, I don't see it very much in non transplant patients. Of course, I work do my inpatient work at UC H and they have the sort of picture of when the last MRSA case was, it's usually months or even a year ago. But transplant patients are different, the VRE and Lunes resistance. I'm old enough to remember when Lunz was introduced So resistance happens all too quickly with antibiotics. ESBL. S are a big problem both in transplant and non transplant patients. Of course, and acinetobacter as well. So always discussing microbiology and infectious diseases. Of course, working in a non transplant center, you won't have the luxury of them coming to the ward in the morning, you will in ICU but unlikely elsewhere, but please do get in touch with them. So the increased risk for transplantation, again, bilary tract manipulation, of course, those who have to have stents inserted cp following transplantation, any radiological procedures or even surgical procedures will increase the risk, prolonged hospitalization, I guess goes without saying likewise, mechanical ventilation who have indwelling vascular access or urinary catheters. Of course, these things need to be checked and sampled and don't be afraid to remove the cannula if it's been in too long. I remember one sad case of staph sepsis from a cannula that seeded to the spine and the poor patient was unable to walk uh prior colonization. Again, you probably won't be aware of these data. Um If you see the person on the acute take, but there was a study showing these Carbenin resistant Klebsiella patients that were positive from rectal swab became active post transplant with immune suppression. And again, in this study, what you would imagine to be the risk factors, increased hospitalization, higher meld score going into transplant, prior antibiotic exposure, ICU, et cetera. And there is a program currently to transplant. A CLF patients who, of course, by definition will be sicker, going into transplant will almost certainly have a lot of antibiotic exposure and will have longer icu lengths of stay. And so these people are particularly at risk surgical side. I'm, I'm, I'm not a surgeon, don't, don't pretend to be. But again, the, the you must work closely with surgeons, about 10% of infections will be surgical sites. Um usually intraabdominally, um increased risk, the more complicated the the surgery biliary reconstruction in particular, often these there is rather a radiological solution to these and again, within transplant centers. Of course, you'll be well aware that we have to and enjoy excellent relationships with our biological colleagues. I know it is more different, more difficult on the acute tape, but again, many of them will be very skilled. And if you get some advice from the transplant center, you may be able to manage these things locally, surgical debridement, the vacuum wound closures you'll be aware of. And again, these bugs are, are staph aureus, enteroccus, e coli cetab pseudomonas. So, so broad spectrum antibiotic cover, please bloodstream infections usually most commonly, first month after transplant, always, always, always perform blood cultures prior to starting antibiotics. Please remember rejection. Colin spoke, spoke about this far more eloquently than I would. But do do look into this, please do consider endocarditis. Um This can be a very real problem and with tragic sly, of course, and once again, antimicrobial resistance. Just be aware. You've got to look for these things. You may be able to discuss this with the transplant team as to what might be the most appropriate antibiotics before the cultures come back. Um, want to six months, these are probably the most different to our, to our normal liver patients. The opportunistic infections, aspergillosis, cryptococcus, toxoplasmosis reactivation of TB evidently vaccination and prophylaxis PCP with cotrimoxazole CMV, et cetera. And of course, the most of the febrile illnesses are actually viral during this period of time. Please don't forget the possibility of rejection and also use your common sense. You know, you're still doctors, you may not have experienced transplant but don't be scared of it. Standard community acquired infections can occur. These people can have standard strep pneumonia and you've got to look for these things and treat them appropriately. The recurrent cholangitis is probably a little more specialist, of course and surgical anastomoses, et cetera, there'd be psa is a horrible disease. Uh And uh sadly, it does does recur but uh that that it's pretty rare, of course, tuberculosis. So, so this can recur and as Colin mentioned, they, they are sort of differing regimens, ison prophylaxis for those at risk. Now, of course, you will all be well aware that these drugs can make the liver blood tests go up and there's often a bit of a battle between treating or prophylaxis for the TB and the liver enzyme monitoring. So again, have to work closely with the transplant team, but the overall mortality can be very high in reactivated TB. So please look for it. Please do the test and please take advice. So PCP again, I guess from my generation, this first came on our radar with, with HIV or AIDS as it was called. Um this is falling. We're much better at managing it. There's no real liver consensus for cos mo is all prophylaxis. So again, um do liaise with the appropriate transplant center viruses, they can occur at any time, as I say, most commonly, between one and six months, the herpes viruses can, can reduce host events and you can get other infections. Of course, the infections can be triggers for acute and chronic rejection responses. EBV and H HV. Eight can cause post transplant lymphoproliferative disorder and cancer papilloma viruses. So fairly nasty stuff. Influenza, make sure you're vaccinated the data. We published a systematic review and there isn't much data but the data that is out there suggests it's effective in cirrhosis and liver disease and that they do mount an immune response. So do get vaccinated and do look for them. You know, we sadly had to become more anti viral doctors over the last few years. So we do look for it much more than perhaps we did pre COVID and they can be effectively treated Hepatitis B in those at risk can recur again, these people are managed pretty carefully. Now, the third generation drugs, a very high barrier to resistance and very effective and really have very little in the way of side effects. We do still give the immunoglobulin. Although it's very expensive and in fewer and fewer people, the active immunization hasn't really shown great successes and there will be more effective drugs in industry who have developed them, they have more toxicity and we'll see if they have a role, post transplant CMV. Again, opportunistic infection can cause rejection, graft loss and can be very serious. Um The organ donation, there's no contraindication, those with the latent CMV. And of course, the donor, positive recipient negative is the highest chance of recipient morbidity. You can get de novo infections as well as reactivation and again, highly effective anti viral agents. So please take the advice. Do the tests check the PCR as Colin said, if it's high, treat the the herpes viruses again, no contraindication for the donors with latent viruses. So again, people are at risk. This, this is assessed locally at the transplant centers and those deemed at gracious risk will beyond antiviral prophylaxis. Again, it's difficult to gather large scale evidence and it would seem difficult to have a trial in this area. You wouldn't want to expose people to not getting appropriate treatment. Of course COVID. Now, I think some of these data here are probably a little more severe coming from the first or second wave. We're much better at it largely in transplant recipients. They're perhaps a little more symptomatic but their mortality rates appear no different to those of a similar age matched cohort. Of course, in decompensated cirrhosis patients, things are very different, but that's not what we're, we're talking about. Evidently, vaccination against SARS COVID is a priority and the sero conversion rates are fantastic. Um, and in Italy, they used COVID graphs and it appeared not to be a problem just so I put that in out of interest really. Um immunosuppression. Colin's spoken about this and it's not really my area of expertise. The dosage is reduced over time balancing, of course, normal liver tests and low risk of rejection over time against potential harm of the adverse effects of these drugs. It tends to be a much more individual approach of course. And immune suppression can be adjusted according to the patient's clinical condition in those who develop infections. But please please ask these decisions are not to be made without speaking to the transplant center. And again, many approaches now to minimize immune suppression as best as possible. And after six months, as I say, they, they, most of these people are are are far fewer infections, they're by and large doing pretty well. Uh The opportunistic infections usually only of ongoing rejection is an issue and they're needing further intense immune suppression. Otherwise there are risks of pretty similar to the general population. Always look for HEP B, recurrence, hep C isn't so much a problem now with the world beating drugs, as of course, it was preceding these. So, but best checked for these things. So to conclude, so don't panic liver transplantation, the livers are far less immunogenic organ than the kidney. It's much easier than the kidney. The surgery is key here. But infections are the biggest medical problem and they still affect up to 80% of people. Despite all the advances that have been made, there is an increased incidence of MDR infections as there are across the globe. And we're not at a stage where people aren't being transplanted for MDR infections. But, but that of course may yet happen. And so I think what I'd like to leave you with is some very common sense approach around infection. And I know it's not terribly fashionable or scientific, but um we don't want a world without antibiotics. So contact isolation, hand hygiene. Please please please do all these things. Antimicrobial stewardship. Please talk to the microbiology ID. Doctors at your local trust do adhere to the local bundles that have been developed. I think these things work best as a multidisciplinary team and please don't be afraid to contact the transplant center. They're expecting you to do this and remember they've got access to the surgeons, specific ID specialists and the pharmacists. So they can bring a lot of expertise. And I think there will probably remain a lack of definitive research in this area because I think it is very difficult, but maybe one day I might try my luck with some infection clinical research here. Thank you very much. Thank you very much prof um That's incredibly useful talk especially for user s when we definitely get scared on the take with these um with these septic transplant patients. Um So yeah, so I think we can nicely move on to some questions. Uh There's quite a few. So we'll see how many we can get through. Um Just from flicking through, I think there's a few that are around immunosuppression management um might be worth just sort of banking them together. So um t what um what sort of T levels do you aim for generally with transplant renal transplant? Um whether you have to change, um whether you have to do anything regarding uh if they go to surgery. Um And then I think there's one if there's a, is there a difference in tact levels between new transplant recipients and old? So, yeah, I saw those questions coming through and uh so when I said check attack level, it was with a view to the transplant team making adjustment on the basis of that T level. So it's not an expectation that you would check attack level and then know what to do with it. Um But just for information, um in transplant patients, we are generally using uh generally aiming for something between five and 10 depends a little bit on the situation, we tend to aim a little bit higher early on and then after 3 to 6 months become a bit more comfortable with a lower level. But there are all sorts of reasons why for an individual patient, we may change uh that so um maybe handy to have in your mind that somewhere between five and 10 is in the right ballpark, but do not change the dose without discussing it with a renal uh team with regards to what we do when somebody's sick. Um, this is not uh particularly evidence based, but our general thinking is if somebody's got a nasty infection, then probably better to try and reduce their immunosuppression burden. Although that's gonna take a few days for any dose change to take effect. But our general approach is that we double up the steroids for, for a stress response and omit the mycophenolate, um, unless it's fairly mild infection. Um And then what do we do if the patient can't swallow? Um So for example, they're going for bowel surgery or something like that. Again, it depends on the, the situation we can give all the drugs intravenously. Um, although it's quite challenging to get the right dose of, um, tacrolimus, my friend. And as I said earlier, what we'll often do is we'll give hydrocortisone intravenously and we'll, uh, give the tacrolimus sublingually and we'll miss the microf friendly out for a few days, um, until the bill they can, they can take by mouth again. Um But that would be our general approach, but I would absolutely stress that should be done in conjunction with the transplant team. Thank you very much. Can I just, just to, just to add to that, obviously, with the, with the immunosuppressing levels, um If you're in a transplant center, obviously you get them daily if you're not so much that that can take days. And how, what would your, what just answer the question to both of you? Really? What, what would your general advice be to teams and, and obviously they'll contact you. But would you rather things continued until they had that chat stop until they have that chat or just vary? I think that it, it depends on how sick the, the patient is, but in general, I would carry on with what they were on before until you've got a level back. Um because um that's probably the path of least regret. Um But obviously if they're very sick with infection or they can't take by mouth and that's a different, different situation. Um So what kind of, um I put this question to um Alistair, if that's OK. This um in patients who are critically unwell with sepsis, would you have a low threshold for stopping mycophenolate or other immunosuppression? Yeah, I think so. And I think as Colin said, I don't do anything in isolation. People will pick up the phone and they will then seek advice from the boss on or micro. So, don't be afraid, don't make any rash judgments or decisions that you might regret. But certainly, yeah, you would consider, I think reducing or stopping. But I think Colin's advice at the beginning is the right view. Keep them on what they're on. If that's been getting them through the most recent, few months or even longer, then it seems likely that that's going to be a major issue. And sepsis icu you do, you've got more time than you think, haven't you? The dosing is given twice, twice a day, you get the levels off, contact the center, update them if things change and take their advice. Great thing. Awesome. Just seeing what else is here. There's, there's a couple there about um um the trimethoprim. So there's one does trimethoprim cause type four renal tubular acidosis. Yes, that's correct. So that's hyperkalemia with metabolic normal metabolic acidosis as well as its effect on, on creatinine. Um And then somebody's saying, well, if, if trimethoprim is only increasing the tacro sorry, increasing the creatinine because of a tubular effect that is not harmful. Why do we stop it when the, when the blood test comes back? Well, the, the you, you can argue that you don't need to stop it. But the problem is that you can't tell whether it's just the trimethoprim or there's something else going on. So it's clouding the issue. So that's why um people often, often stop it. But if you knew for certain that the rising creatinine was only due to the trimethoprim, then there's no need to stop it. I think it was something about Ston Cholangitis and, yeah, I think at the major center, I think so. Yeah, I don't think, I don't think you'd want to take on an E RCP unless you're used to it in these patients no matter how skilled. Um, and there's other question actually, um be interesting though, not really experienced this myself much at all, but um any advice on management of overdose, intentional or unintentional of immunosuppression? Um Yeah, I, you were, yeah. U usually the advice is you have to just set it out until, until the, the levels come down. Um That's it, paracetamol overdose as well. Like likewise, I treat as, as you would any, any paracetamol and acetylcysteine organ support. Um So, yeah, absolutely. Don't lose your head guys, you know. OK. They've had a transplant but it's still by and large acute medicine. Somebody's asked as well, what's the maximum dose of furosemide? Um So when I was a trainee, we used to use, we sometimes use 750 mg twice a day. But to be honest, II don't go above 250 twice a day. Um Cos I'm worried about deafness and, er, if that's not working. Um and I'm not going to do ultra filtration, then I would add in a Thiazide diuretic and just to blow another myth. Bendroflumethazide is exactly the same potency as metOLazone milligram for milligram. Uh There is one that's just come in um when it's a good time to restart immunosuppressants following admission with an infection. Should we always wait for antibiotic course to finish? Or as long as um as long as over the septic phase I II think it'd be case by case, wouldn't it Colin I and I think, yeah, the mantra of completing an antibiotic course is, is, is, is of course not evidence based. We don't know whether we should be giving it five days, 10 days, 15, etcetera, of course. So I wouldn't, I wouldn't be too dogmatic, but I think it's case by case. Yeah, II certainly wouldn't wait till till afterwards because the patients can certainly get rejection. So you really just wanted to make sure that they're, they're getting better, they're beginning to get better. So it's, it's usually only 2345 days, something like something like that. I was always worried during the COVID, the huge number of patients were being contacted because of COVID and advised to withhold their mycophenolate until they were better and a lot of them were coming back to the next clinic appointment three weeks later, having still withheld it. So II just worry that uh they withhold it for too long. Mm. I think like one final one here is um for patients on cycloSPORINE. Do we need to take levels for those and what's acceptable in terms of levels. Yeah. Um yes, it is worth doing a level just like the tacrolimus level. Um and I would say exactly the same thing that the reason for asking people to take a level is not cos I'm expecting them to change it, but so that they can then speak to the transplant team and say uh here's the, here's the level. But basically, um we are usually looking for levels of, of, of in the long term patients of something like 75 to 100. Great. Thank you. I was just coming to the end of the session. So I just want to say thank you to Colin and Alisa for fantastic talks. Um Learn a lot. I didn't realize Bend and metOLazone were equal dosing in cardiology. We love using metOLazone and Bend doesn't work. So that's a really good knowledge and it's always great to know there's always a happy renal and liver reg on the other side of the phone to call for help any time of the day. Um Thanks a bit criminal and Emma for um sharing the sessions on the questions. I hope everyone found the format useful. I'm gonna um release this feedback form on medal. So please do fill it out. Um But be really grateful for your input and see if um you find this format useful and once you complete it, you'll also get a certificate for your attendance. Um Our next event is on the 24th of um April which um will be circulating um soon and that's gonna be on graft rejection. Er, and in the interim, please do have a look at the website. Um We've got lots of information on there and also, as I said, the elections are open. So if you're interested in joining us and we'd be really keen to have you. Um, we want physicians to have a greater say on the future of transportation and share our learning and experience. So thank you all and have a good night. Thank you. Thanks very much.