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Progress in Alcoholic Hepatitis: Has there been any?
Prof. Mark Thursz, Head of Digestive Diseases Division, Imperial College London,Department of Surgery & Cancer, London, United Kingdom
Thursday, May 9, 2019 · 6:06 p.m. · 42m 09s
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this is hepatitis a pen and the reason it's a mail before female is they comes before
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uh be so sorry colour uh okay does that work or do
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i need to know if it's as good as that one uh
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okay
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okay fantastic so uh i'm in
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thanks very much little rises for obvious and responses
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for the ability to be here quite exciting quite a
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good day for us having a torrent your sissy in
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your department ah but maybe a little explanation the title
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so we ran between twenty eleven twenty fourteen a trial called stop but
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and stop uh um was steroids open source
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file in for l. collect hepatitis too old treatments
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and the end result so the trial was an open source find doesn't do anything the troll for this condition
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and stewardesses of both light significance in it if anything in the
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end of it one or two people said well what progresses the bin
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um i act after two and a half million pounds with the trial than four years
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of effort in sixty four different centres across the u. k. yeah that i was little me
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so yes there has been some progress and out in the next few
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minutes i can come been she so mine so i'll patients you drink heavily
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um actually i is always surprising the majority will get facts in the liver if you're drinking heavily
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because the end of the day ethanol is just another uh
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as source of carbon i which eventually ends up as fact
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um but only twenty percent will get we
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inflammatory component the ballooning i the uh uh
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cats sites uh the inflammatory infiltrate my reading
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bodies et cetera uh progress to also races
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and of course majority this we don't see we actually and he's we we tend to see
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as clinicians two things one is patience you present with the compensation
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or accuse increment the buffet via and then have the patience to
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uh who present with our comic appetite is which is
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an intriguing condition that affects maybe twenty to thirty percent
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uh of patients with um i'll i'll call
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use disorders ah and um and severe liver disease
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almost invariably the patient has advanced fibrosis probably eighty percent
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of patients have some races ranging from uh these roses to
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frankly a liver that is just a a
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college and max with the few remaining impact assaults
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so uh what i want to have a of that's human it says some pretty progress in diagnosis treatment
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infection which is one of the major complications and some
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and nice stories about about a target a novel target discovery
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so in terms of diagnosis they are three o. four
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and i to play a consortium that came to consensus
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on a on diagnosis a definite how collect hepatitis is a
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condition that is diagnosed clinically and confirmed his to logically um
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probable is clinical diagnosis but no confounding factors and impossible is
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well we think it's probably alkali kept us 'cause the patients drinking a bit but maybe they have a
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also hepatitis c. at the same time or maybe
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they would taking a co mock sick that i have
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uh oh some of the truck that might cause daily or
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they've got some possible so antibodies although which are relatively common and
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the argument would be that all of those patients impossible
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should have a biopsy and if your french or belgian
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then and after the everybody was suspected laconic appetites should have
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a a liver biopsy in yet all these patients almost by definition have quite a lot with a
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ah and uh they they have only the trends
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jugular the biopsy for which a sometimes it's feasibility
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can sons those delays in getting the biopsy ah
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and anyway what does the biopsy really tell us
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well the typical his logical features of our colour kept tight is you've got
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balloon to pass aside she got fact you got inflammatory cell
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infiltrate she got uh these moderating bodies you got megan mitochondria
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but a lot of these features are the same as the patient walking the street would match
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as most of you revise that they're not that different the degree
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fibrosis is a little bit more expensive maybe on the on the eh
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blue college in staying there with perry cellular fibrosis the two
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features that perhaps it's a logically a different is the bile plugging
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associated weakest basis and the and the mega mitochondria otherwise
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there's no difference ash nash it there's no nothing that tells you this is um alcoholic hepatitis
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and and number was a lot over the years this is based around a hundred and sixty and seventy biopsies from stock
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but to say well if we just call it on clinical
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criteria how good always so or probable outcome like appetite as
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uh uh we good calling that the answer is if you do the biopsy quite quickly
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uh here in the first couple days after admission uh the balls on the left that
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they then the answer is yeah we're pretty good ninety percent of the time we call right
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we call it right in i i. e. the patient has to
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have to hepatitis and and maybe some other features on the boat
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if you leave it since it if you leave it on the patients been treated the steroids and
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some of the features particularly inflammatory infiltrate will will and not uh unexpectedly they will lose all of
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and so the we we you can say that the uh we don't get
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it right quite so frequently all these we call come from his to logically
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but actually would like not to do a biopsy if you're an american you never do a biopsy
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for suspected alcoholic hepatitis for the very uh uh
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clear reason that the insurance companies won't pay for
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it nothing more than that not because it might or might not benefit the patient is that payment issue
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so we have have started looking it up patients so for by marcus to help with the
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diagnosis in one row we've taken is a a method dynamic so much to the limits approach
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uh in this case how guessing by last isn't looking at
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the whole bile acid profile in operations without colour kept titus
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verses usable controls and healthy individuals and you
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can see from this unsupervised analysis yeah but the
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the the patients separate out quite nicely with the healthy controls over here in the l. caps
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uh patients are over there which is quite encouraging given that's unsupervised in our seats
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if you do a supervised a principal components analysis looking at specifically
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u. t. compensated strokes it's verses i'll call it kept tight as witches
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fundamentally the b. diagnostic conundrum you'll facing
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then they still separating out quite well and if you dive into this
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you can identify the bile acids appeared to differentiate these two could conditions
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ah and basically it's torque telecast it and like a weak acid uh
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all for some reason enriched in in the i'll call it kept items
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patients obey quite a lot of these bile acids or increase compared to be healthy controls
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what if you try news all of that policy profile in terms
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of uh being a diagnostic by a marker actually performs incredibly well
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uh i am patients would come for um his logically come from the local like uptight as
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and if you just separated out and if you just go
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for specific by last it's then you still get quite a good
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uh on targeted a bile acid profile you still get a
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good diagnostic performance soap passes is one way that we might
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um uh get away with not doing a biopsy assuming the cause you get a
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by last agreed out in the two or three days after the patients that message
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the other by market that is of interest
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is the c. k. eighteen degradation um fragments
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these are uh produce by adopt article on the cross excels
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um we've compare those against the history logical diagnosis was very interesting here
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is uh this is uh the c. k. eighteen a and thirty frank but
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um and well and the uh the the sixty five fragment and then the ratio between the two
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and these are are uh correlated against
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inflation information my readings ballooning fibrosis et cetera
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and you can see for information is a really clear cut
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difference in these levels of see katie not much much higher than
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you see prince and say no not collect fatty liver disease where
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people are trying to use these uh by marker in the past
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that is pretty promising and and as a diagnostic test c. k. eighteen
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has a reasonable performance i mean we probably need some bigger numbers yeah
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um and um maybe look to see what if
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you combine c. k. eighteen with the bile acid profile
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we're not the first to close to look at this so this is a publication from a
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couple of years ago showing that the these
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fragments help to differentiate uh these uh these conditions
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okay this may then from from diagnoses onto a treatment and um
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so this is what the easel guidelines currently say
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basically with the after making a of um diagnosis
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with all would have to live a biopsy and doing infections screens and and such
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like we assess the patient the disease severity and we still use my agrees discriminant function
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are we with the discriminant function break some equal to thirty two defining
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a population with severe alcoholic hepatitis meaning
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that then mortality at at a month
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is over twenty percent three months is over thirty percent so
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this is a and actually medical emergency
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with with a a very significant associated mortality
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and we treat these patients of with it's recommended that we treat these patients
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would put this and with or without and asked assisting get to that later
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and then if they uh at the moment what we recommend is by seven days if
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they have not responded response being a change in the baby rubin or an appropriate deals goal
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then you stop the brightness like uh the argument being the if you
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continue the premise loan you make them susceptible to infection without any potential benefit
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but actually the data is beginning to show that even by seven days
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cheating with the uh brought the minister press it like a pretty this line
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already puts the patients at risk of infection uh and if there's a way of avoiding it so much the better
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so this is the the the results of the of the stop a trial just to summarise where we are
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at the moment so put a pencils volume buses now open source file in
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on on the right there no difference whatsoever and the very marginal difference in survival
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a in um a in the premise alone treated group which is um
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backs up pretty much what we see in a in a
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in a cochran analyses and a and a lot just studies
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the issue is is the primary endpoint in that trial was twenty
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eight days and i i actually be at our aim is to keep
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patients alive a little bit longer than that and if you follow
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the mortality at by ninety days a survival close to complete become birch
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and therefore you have not really done the patient much good it's only given
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a few of the patients a few extra days of survival it it if that
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um i and that probably the reason that you decide you've partially advances a patient
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uh by suppressing information if you just advance
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to the patient by increasing the susceptibility to faction
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someone says population with severe alcoholic hepatitis can we select the population
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a sub population as it were you might do a little bit better
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as a rubber by mark uh what we would now call a ferret
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could not stick idea by market it tells us which treatment to use
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um that might guide our management um and this is really that
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i want to talk to about sixty that's bacterial d. n. a.
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a a very very expensive by marco called and a while and then the c. k. eighteen
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so the reason for the bacterial d. n. a. is this so in the stopper patients we took hold but
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uh extracted d. n. a. from it and did quantitative real time p. c. r. for
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the for the backchannel sixty nice using common primers this is a a quantitative asked say
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ah i'm what you see here this is the uh the the group the weather
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i'm sure not treated the the control group no premise loan
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uh no difference in their factual d. n. a. levels whether they got infected or not
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but in this is the baseline measurement and this is infection within seven days if you talk
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um and once the people with just treated with prejudice learn after measurement to
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the sixty nice was with a high level with formal likely to get infected
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i. e. that was probably quite a lot of got trance occasion of bacteria a circulating in the sixteen s.
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picked up those people who are gonna get uh we're
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gonna get infected a bit as things were building up
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so um perhaps therefore we could decide whether or
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not use steroids based on that uh that by market
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and we went back to the data model what might have happened by doing some matching where
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so if the patients who had high sixteen s. d. n. a. had not been
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treated with premise line and i even match group then the survival would've improved significantly
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so actually because you could use this information in a different way what you could do it because you say
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okay that patients with a high bacterial d. n. a.
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in the blood we could be given them prophylactic antibiotics
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um we possibly can find the answer to whether that strategy
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is good when the um uh the and uh was it called
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there's a trial going on within a matter for
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in leo the moment um and uh he will
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give us those results probably in the rules about p. s. of the meeting
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yeah and a lot is is interesting so this is really expensive by market
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the nature feel too imprecise ratio so given that you get a blog canton all these
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patients because because absolutely nothing on like all the other by mark 'cause i've been talking now
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and it turns out there is as it would just the rice and the loss
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as some of you i i don't know if you put maybe with big goldie locks
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a a story so goldilocks and the three best
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maybe explain every drink so okay that was
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uh it's a fable but there is just the the right uh as what temperature of analogue
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the n. l. r. is lower than the patient has no benefit from brightness light
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if it's high they have no benefit but if it's just
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right just in the middle and the law or two to five
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then couldn't this loan actually identifies a group of patients who will
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a potential benefit why well probably if you're an l. r.
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is low you probably have very little acute inflammation in the liver
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if it's high you may already be brewing in infection
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and it's the ones in the middle who potentially benefit
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similarly c. k. eighteen if you've got a high c. k. eighteen
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i mean this is a really really high seek eighteen and thirty fraction
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those patients with a lot of information in the liver seen also to to benefit
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so by marcus that might help us choose uh uh uh
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what would you trade with pretty slow given that's the only recommended trip we currently have
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so there's still an uh of focus now to infection and
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there are we define different periods for infection the the first
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and um one the most important there is is the baseline a lot of patients without click appetite is
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about thirty percent will have an infection the time
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they're admitted to hospital it's probably part of e.
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precipitating events of i ended up with them coming in and that makes
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a very similar in a way to teach some problem with the fate
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if you have a a baseline infection there isn't a significant difference
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in mortality from where if you don't have a baseline it infraction
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uh whether or not you treated the with pride misled however
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in this topic trial the protocol basically said if a patient comes in with an infection treat that
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infection once the infection is treated then randomised them
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to whatever treatment are never going to be on
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it turned out that some senses was situated the infection the
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stop the antibiotics than a randomised and if they were randomised
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in that situation to receive premise loan the mortality increased substantially
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and the lesson here is really rather simple if you can t. the and if
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you've got a baseline infection you must continue the antibiotics probably for at least a week
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uh after the patient has started the premise one to cover the risk when initially faction
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um i'll on treatment then in incident infection occur more
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frequently in print this untreated patients than in the control patients
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but it's not just during the period the premise line treatment because actually
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appeared why the way out to ninety days so that brought him in
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a suppression process and puts the patient or risk in is probably why
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the uh the use the bible curve stock converging after twenty eight days
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apart from pride in this line however there are other factors that
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play that make these patients highly susceptible to infection one of those
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is it effect in um in fact this site boxer to burst
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and now at the let's see him huge fills and wanna
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sites to hail ingested bacteria soon normally if you get a
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of i guess i traces i'm into these and allies assembled compartments
00:20:07
you get activation of the n. a. d. p. h. o. c. days it
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produces a lot of ocean drive free radicals pick they'll look the the contents here
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this this uh this uh function is defective uh
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in many patients with i'll call it kept titus
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in fact uh you can see that this is as a measure of
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a city bus is quite a range in a patients presenting with this condition
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and if we define as it were a defect in not says abreast as somewhere uh below the median
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then if you've got below the median it's a a very good
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predictor of who isn't going to go on and develop an infection
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uh so actually i also did best effects could be used as a a problem last marker if
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you like but it's also something that potentially we
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can address therapeutic lead to reduce the risk of infection
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what's interesting is if you take mona sites from these uh
00:21:07
these patients and you incubate them weird for our with label bacteria
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uh and and then you are you can allow them to
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you know for a short period of time to killers bacteria
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you can then lies them on the sites and see if you
00:21:23
can recover viable bacterium this case speaker live from on the sides
00:21:28
what we find is that patients compared to healthy controls
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patients without calling hepatitis you get far more
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viable bacteria still present in the moment side
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but in addition to base you um you also it the patients with the most of a
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best effect also to best effect have the most
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bacteria you can recover what we suspect is it
00:21:53
trance located bacteria that the the picked up in the
00:21:57
lab probably in this packet circulation by these mon aside it's
00:22:01
but this act up into the into the it factor sites but then then
00:22:06
not killed and therefore the smaller sites
00:22:07
is circulating like extrusion holes deposits in infection
00:22:13
mainly probably in the poem really compare re backed which is what you get some old
00:22:18
infections associated with alcoholic appetite as i had the other
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new menu reasonable normal uh it's not a normal one package
00:22:28
so i've already said the sixteen s. d. n. a. picks up and
00:22:32
it's probably picking up these bible bacteria in the in the mornings sites
00:22:37
and there's a analogous situation in patients you've had stem cell transplants
00:22:42
you get subsequent infection you find the the majority of
00:22:45
the organisms it cools new men yeah this is recently published
00:22:49
in nature manson but the organisms um the uh cultured
00:22:54
from the new mania are actually also present filer genetically identified
00:23:00
in the get the same page so they got is almost certainly the source
00:23:05
the mono sizes as it were the vector and then it gets too too long it's
00:23:12
so let's change direction i and look at it to a couple stories now
00:23:17
uh focused on finding noble a therapeutic interventions soap
00:23:22
on the stock which probably had a lot of
00:23:24
uh patients d. n. a. um and we got some from colleagues that a
00:23:29
u. c. l. marcia morgan and the group we got patients without call use disorders
00:23:35
to uh i didn't have any liver disease so one of the i i guess
00:23:40
that that the lucky eighty percent to get away with a heavy drinking if you lie
00:23:45
we run a a genome wide scan and this is no surprise to anyone who's been following the genetics of
00:23:51
alcohol on on our call it the disease p. n. p. late three is that if
00:23:55
frankly if we haven't seen this with uh been quite surprises uh as a genetic signal
00:24:00
but in addition to this is a say there's a a couple of other low side which i draw your attention to this will
00:24:07
so that s. l. c. thirty eighty four uh
00:24:11
crimes and twelve was also
00:24:14
after validation was significantly associated
00:24:18
with um with the risk of developing alcoholic appetite it's
00:24:24
now this is a interesting uh gene which i have previously knew absolutely nothing about
00:24:30
as a sodium couple the main about uh amino acid transpose the predominantly
00:24:35
it's taking mutual amino acids is
00:24:38
expressed almost exclusively in fact the sides
00:24:42
um but there's been somewhat previously and we can
00:24:45
eat genesis um some work on the the centre
00:24:50
uh i and some work in the guy after all in crimes disease
00:24:56
collaborating with remember time is group ah um samples i think we've taken boss away and uh
00:25:03
so um he had got our name from my passes sites
00:25:08
from patients without cots of iraq like hepatitis mild alcoholic hepatitis
00:25:14
justice to have to have titles with without
00:25:17
a a a significant inflammatory disease have the
00:25:21
controls et cetera what you can see here
00:25:25
is this amino acid transporters severe the down regulated
00:25:29
uh in operations without colour kept charges so presumably the genetic defect
00:25:34
makes this even worse but we haven't been able to show that yeah
00:25:38
so we did some uh additional experiments if
00:25:41
you take out a serum from patients broccoli hepatitis
00:25:45
i knew incubate a bizarre actuate seven cells or how to control serum
00:25:51
you find that that suppresses the the
00:25:54
patient's room suppresses this a minister transpose uh
00:25:59
and as you know in the in the service patients is every implement results can you could think of
00:26:04
um you you name it it's not regulated so we went through a a whole
00:26:08
list of them the most patient suppressor gene expression was actually file will be so
00:26:16
and if you do the antibody blocking experiment i you take
00:26:20
this serum uh incubators cells but you block i want preacher with a monoclonal antibody
00:26:27
then b. s. o. c. thirty eighty four level goes back up to normal levels
00:26:32
so clearly this is the the the mediator of this so i want
00:26:37
because i'm not quite little biology of awhile wanders two forms out from the beach or
00:26:42
uh the base that we as been well characterised so we know it can cause
00:26:47
state houses activates tell it sells amplifies information
00:26:52
uh has some effect on the get um and can cause a pass like there
00:26:57
so this is an animal model uh all data from an animal model
00:27:01
i'm looking at what happens if you uh increase
00:27:05
i'll will be so it increases the amount of fat
00:27:08
uh increases the amount of information in the liver in this
00:27:12
mouse model and then if you block a it's the cast will
00:27:16
so the production of a one requires is cast space if you
00:27:19
knock that out then i want beecher is not produced and you
00:27:24
you return to your baseline phenotype so i want teachers pretty important in this condition
00:27:30
and as a result of this there are two trials are going on so one is just
00:27:34
reported just like the old trial of using a a receptor blocker called and i can read
00:27:40
so this was data that was um uh presented that
00:27:43
yeah so the last year by john g. jobless group
00:27:47
with a marginal benefit another trial uh hopefully will be completed by the
00:27:52
end of the year ah and this is using a monoclonal antibody saw
00:27:57
getting um uh i won't be so the medical school kinda kinda map
00:28:02
so uh hopefully we'll have some more data to show you next year
00:28:09
completely different direction so i want is is one
00:28:12
utah get a and here's an introduction to other
00:28:17
the tension you taught says is uh oh what that we've helped a room
00:28:22
on without somewhat so this is a
00:28:24
gene expression analysis in in alcoholic hepatitis
00:28:29
and if you compare at that so this is comparing with other
00:28:32
disease groups unhealthy controls you say yeah okay patients definitely separate out
00:28:38
and there were two hands on proper analysis there are
00:28:41
basically two patents to regulate three things are going on
00:28:46
you can deduce all dissected as it were from gene
00:28:49
expression mouses want a is basically are around a p. paul
00:28:56
uh alpha and the other is really a round
00:29:00
um and h. and f. uh for alpha so
00:29:04
this is a uh the actual uh this marker uh i get
00:29:10
yeah oh yeah she buses um buses mobile so these are the patients was data uptight is what
00:29:17
walking well okay so mainly around the the changes that you see a a
00:29:23
driven mainly by the up uh uh by break this regulation beep are alpha
00:29:29
whereas if you compare those with the ones with frank
00:29:32
alcoholic hepatitis is mainly a around h. enough for elf
00:29:38
yeah i enjoy the four of us quite interesting 'cause there is a there are two ice a form so
00:29:44
um ones as it were feed twice a form which is of
00:29:47
the p. to an adult one which is it is p. wall
00:29:52
it turns out that in our colour kept i just the p. one is to press the peaches up regulated
00:29:57
but the p. two does not do the same job is
00:30:01
p. will it it it doesn't switch on the same genes
00:30:05
and so in fact you've got over audi got suppression or rather than a anything increasing
00:30:12
u. h. happy to suppresses a number of
00:30:15
a pass like functions including how the main including
00:30:18
the enzymes required for by lasted synthesis all by lasting expo et cetera et cetera
00:30:25
so you actually got um uh i you know at a situation here
00:30:30
which perhaps isn't so surprising where you've got what
00:30:34
looks on the microscope like a healthy approach aside
00:30:38
but actually it's being switched off its function is switched off penn should get
00:30:43
the characteristic features of liver failure uh you get quite
00:30:48
a lot with a and you get colour spaces so
00:30:52
almost sundays explains what is going on i three look upstream
00:30:56
all the age enough for l. for there are two main things of
00:31:00
the driving it t. t. f. pisa um and uh e. g. f.
00:31:05
uh and actually most of it is around tedious pieces there's plenty tedious speech
00:31:10
around a city via a beaches seems to be causing some of the does regulated
00:31:16
uh h. enough for our for a production and if you block it's the new
00:31:21
rich uh and some of the the gene expression of of some of these things
00:31:26
uh back to mobile so somebody's metropolis the enzymes uh and indeed to q. genesis
00:31:34
what's interesting is that people are ah a gamma and and asia for a perhaps of the reciprocal of facts here
00:31:41
um and so i i actually if you switch on p. part um
00:31:47
if if you switch on p. program at all or if you actually use
00:31:52
um as a a and i get a searches rose eclipses and
00:31:57
actually the you can restore or this is obvious in cell lines
00:32:01
you can restore some of the normal cell function back back to normal
00:32:05
so a potential for up you know resin which are no good the pike bits and theoretically would
00:32:11
do the same thing so opportunity that the unit
00:32:15
to explore something that will return a liver function
00:32:20
one other story this is not already story but i four would include
00:32:24
it 'cause it's kind of interesting which is the fact that you can transmit
00:32:28
susceptibility to alcoholic well sort of hepatitis sort of you i my site never believe
00:32:36
a proper all collected to toss it but not nevertheless is sort of our cat
00:32:40
in a mass term so susceptibility can be modulated
00:32:45
with the micro by remote patients so if you to healthy
00:32:48
controls or you um what's to from healthy controls all still from
00:32:53
uh i'll cat patients it changes a susceptibility to
00:32:57
information so this was published a couple of years ago
00:33:00
hi in gaston is really very provocative the idea that something in
00:33:05
that um and that still something in that market byron changes you susceptibility
00:33:12
and there's a term that i really hate call this bios is when it comes to
00:33:16
fickle transplants and i got market by um research we've talked about
00:33:20
this place is is if we knew what normal or you biases walls
00:33:25
um and and the pursuit is ever for the individual organism most pieces of is
00:33:32
is responsible for disease and it's quite clear the we're
00:33:35
unlikely to find individual bags it cools disease may be ready
00:33:40
be well but in general with that's not what we're going to find what we're going to find is that the function
00:33:46
functions all sets of functions within
00:33:48
those michael bahrain's varies and changes susceptibility
00:33:53
oh all the the metropolis they'd generates may well influence
00:33:59
i the metabolism or inflammatory or immune responses and
00:34:03
those various examples already have published of that it's
00:34:09
so whether they have a a a good scientific basis for so not
00:34:15
a couple of groups of already started doing fickle transplants in order to
00:34:19
uh address uh i'll call it kept arts is where there is no treatment so
00:34:24
in india there's a whole list of reasons why not to give storage narcotic appetite as
00:34:30
although i still to disagree with them less but i kind of agree with the concept
00:34:34
that but well there's one very good reason not to use too that they just don't work
00:34:39
ah but nevertheless they take these people i caused erode ineligible patients and they gave them
00:34:44
fickle transplants and they this is just the most incredible a
00:34:48
survival curve change which i very much doubt actually i have
00:34:55
ah we just don't see that level all mortality and so
00:35:00
quickly in our i'm patients the european populations but never the less
00:35:05
i think there's a very good rationale for doing this and doing it properly and
00:35:09
using it to work out what exactly is so cool despotic uh a micro why
00:35:17
so i'll finish yeah but with a acknowledgements
00:35:20
for michael exhibit imperial college uh at u. c.
00:35:23
l. help with the the genetics a king's um helping with some of the sixteen s. where
00:35:30
uh it's forty odd senses of the collecting patients for is in
00:35:35
the stop a group or moan and just really that i'll jamie
00:35:39
who uh who did the original for alpha story thank you very much attention
00:35:52
right thank you so much on this presentation so the uh several questions
00:35:59
please feel free or otherwise i would like to start one so regarding uh so
00:36:04
if you have responders to store its uh_huh true than for this with forty milligrams
00:36:09
so do you stop the draft of the tapering oh yeah this is
00:36:13
a really good question so actually we we in the trial we stopped immediate
00:36:18
and in fact uh we have done some studies in the past to see
00:36:21
over these patients becoming at the sony and and and such are so they have
00:36:26
i see a lot of people would live a very how how have some degree
00:36:30
of uh uh you know that to produce the record stores very well but actually
00:36:35
forty milligrams for four weeks doesn't really have any effect on metal
00:36:41
so i will not say i discern in prices immediately often drew
00:36:48
also i
00:36:53
off
00:36:55
oh yeah oh yeah yeah so uh uh so there's a lot of
00:36:58
issues about fungus so there are a number of papers are you aware
00:37:02
about fungal sepsis um some groups seem to find it more frequently than others
00:37:07
and i actually might well explain why when we've had the patience harder broad spectrum antibiotics
00:37:13
we still have so scratch criteria and i'm for show we should be sensitive button treat for fun guy
00:37:21
we have really pour diagnostic a test the fun guy most microbiologist don't seem to
00:37:27
be able to buy which uh detective there's a beach ugly kind essay which is
00:37:32
maybe a little bit better than coach uh but not a lot
00:37:37
and we're currently working on an eighteen s. uh a p. c.
00:37:41
r. test to see if we can improve all all taken so yeah
00:37:47
a fun guide uh in one of those neglected areas for sure
00:37:55
you do
00:37:59
e.
00:38:01
oh
00:38:05
i didn't feel i could throw in nutrition on top of all those other stories at the
00:38:09
same time but attrition is not an ad on nutrition is it is critical so the reason
00:38:15
um the reason gastric paper by chris often reno basically in the illustrated
00:38:21
uh one thing that if you eat enough calories than your survival
00:38:26
your risk of infection your risk of acute kidney injury old improve
00:38:32
the problem with this group of patients is some of the uh profoundly undirected
00:38:37
and they will not eat and you sit at the end of
00:38:40
the bed in you offer them cartons of high protein high calorie stuff
00:38:45
and it's still there the next day they just won't touch it
00:38:48
that's in itself is kind of an interesting yeah we're why why divinity
00:38:52
i suspect very much uh some of the society whole mine's a completely this regularly
00:38:58
what grade does trial showed the is a intensive therapy by sticking is it needs a gastric chips
00:39:04
does not make a difference in the reason why is because
00:39:07
half these patients recover pathway and those they start a poll a
00:39:11
you know cheap down such art and that with aspiration pneumonia also sometimes like
00:39:16
lucas balances pour survey and that guy it you know getting debates it tight complications
00:39:23
and and so we have to be very very cautious about uh using mesa gastric phoebe
00:39:31
but there is no uh there's a lot more to be done there there
00:39:34
was a time yeah in i think between that and the amino acid transport
00:39:39
i suspect that you're not getting enough amino acids into the path aside it's
00:39:44
to get good protein production and that's exacerbated in those
00:39:49
patients of not eating so it's a very good point
00:39:55
you will see that there's a lot that humans will be the one that does like within that is
00:40:03
what you up regulated responses to more specific so the opposite would be like for example the one i goodness
00:40:10
is that it it on this and there was a little bit of data
00:40:12
from shopper chose his group suggesting that yeah that that maybe that would be
00:40:17
i'm very cautious because we have had to set up
00:40:21
recently specialist clinic for checkpoints in a bit uh hepatitis
00:40:25
because around us all the oncologist to a widely
00:40:29
the volume outcome bruising lab et cetera so widely use
00:40:33
we had to have a special permit for patients with
00:40:36
the liver related complications and the special scott for anything else
00:40:43
and isn't this one question
00:40:49
ah yes so so this is quite this this is quite interesting one
00:40:53
trial and then asked l. system i read a provocative promising results suggesting
00:41:00
improved survival never been repeated uh well interesting
00:41:05
finding so if you go back i'd actually isn't
00:41:08
data about recovery of viable eco live from these
00:41:13
moments sites have uh not to to burst effect
00:41:16
if you incubate those cells with anna style sixteen
00:41:21
in fact the also to best in previews and you
00:41:25
reduce the number of viable bacteria so there's a mechanistic lee
00:41:29
there seems to be a a as well as with the empirical clinical data a reason for using it
00:41:37
and then i like put this line which definitely does can do ah on innes assisted doesn't
00:41:43
do anyhow i mean a few people got bit red in the face but what does that matter
00:41:48
the red sort of offset some really ellen us maybe i don't know that the colour palette
00:41:54
but so actually i we're using an s. l. system a little bit uh yeah
00:42:01
yeah
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