This is very interesting to see on here. My mother was the dissenting vote on an FDA panel on this. There are articles about it. I'll copy her words (as reported by something but seems legit)
> She said that the FDA's plan doesn't go far enough.
> "It's hard to dismiss an anecdotal report when you are the anecdote. When a patient is finally tested and found to have gadolinium retention, there's no FDA-approved antidote. So what does the patient do?"
And I want to reiterate that she was "the" no not "a" no. I don't know if her vote alone is what's caused more research into this. But it's probably the thing I brag about her the most. Even though everybody else said it was fine or abstained, she stood strong. If you look up the articles from the time of the panel (2017) you'll see a lot of articles about this panel and how she was the sole no vote. Included in that was a public post from Chuck Norris praising her. He was going to come out to meet us but I think it was a bad Texas hurricane season so that fell through
In case anyone is wondering what Chuck Norris has to do with all this:
> Chuck and Gena Norris filed a lawsuit against several medical companies in 2017, alleging that a gadolinium-based contrast agent used in Gena Norris's MRIs caused her to develop a condition called gadolinium deposition disease and resulted in debilitating symptoms like cognitive issues, pain, and muscle wasting. In January 2020, the Norrises, along with their attorneys, voluntarily dismissed the lawsuit with prejudice, meaning it cannot be refiled. The dismissal was made without a settlement payment, and each party paid their own legal costs.
It might give a glimpse into his worldview to mention that during the COVID pandemic Mr Norris shared an article on social media that claimed that the COVID vaccinations killed millions of people. [0]
His reaction is kind of the essence of populist backlash.
People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the experts are human, fallible, and sometimes incompetent or corrupt.
Since the original message was one of unqualified absolute faith in the experts, the backlash is to flip over to believing that the experts are satan incarnate and pure evil and always wrong.
It reminds me psychologically of the arc of an immature relationship. First they’re perfect, everything about them is perfect, they’re going to be your soul mate forever. Then you catch them in a lie or they do something embarrassing. Then you get the screaming breakup. Everything about them is the worst now and you never want to see them again.
A large portion humanity seem incapable of embracing uncertainty and nuance and are over eager to embrace whoever is willing to peddle certainty and simplicity.
As long as that is true it seem naive to believe that nuanced institutions can exist as dominant entities in human societies.
This is true, but it is also true that "official" communication often tends to project level of certainty that just does not correspond to the actual level of knowledge, and Covid was pretty bad in this regard, because in absence of actual knowledge, hard recommendations were being issued to people.
Saying sincerely "we are not yet sure if Covid spreads by touching surfaces" etc. would have gone a long way.
I am not even touching the dirty topic of "practise societal distancing unless you go to an anti-racist demonstration, because racism is worse than Covid". That alone probably sunk the levels of trust for a generation in the US, especially among people right of the center. Politicizing science is suicidal.
Back to normal uncertainty. It was the same with various dietary recommendations. Older people remember several major overhauls thereof (are eggs fine or not, and in which amount?), and again, these were presented with a level of certainty that does not correspond to the actual - somewhat fuzzy - state of nutritional science.
You can only do this so long before unleashing an epidemics of distrust.
IMHO, "short term uncertainty" > "long term distrust".
I don't like the "common people are too stupid to be told the truth" attitude (which includes uncertainities).
It is both too smug to work, and unworkable in today's networked world, where those same people will notice really fast that someone is treating them like idiots, and react with resentment and loss of trust.
That is the new enlightennents main project, researching these retardations, building societal implants to overcone or at least life with them. Handling the eldritch horror moments where we can not or the handicaps are societal load bearing and future crippling. The faces they make when the dog dies you can not unsee.
> People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the experts are human, fallible, and sometimes incompetent or corrupt.
Try
People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the authorities and experts, in the name of “the greater good”, actively suppressed debate, knowingly mis-represented uncertainties, pretended reports of serious adverse reactions to vaccination were not only impossible but simply fear-mongering from the uneducated, and then pressured social-media platforms to take down factual information when it threatened the official narrative.
This without even touching on the fact that the WHO, who has one damned job, refused to even declare a pandemic and spoke against any travel restrictions or public health measures outside their lazy guidance until the virus was confirmed to be spreading out of control in nearly every nation on earth.
Having lived through this, observed it first-hand, read the studies, having dozens of anecdotal evidence on top from near friends and family, and still not able to even question the new mRNA platform publicly without knee-jerk backlash and demonisation, has done more damage to my faith in institutions and the medical community than anything else I’ve witnessed in my near forty years on this planet. Covid made crystal clear to me that we still live under tyrannical dogmatic rule devoid of scientific nuance because it’s “for the greater good”.
The claim that it is not possible to "question the new mRNA platform publicly without knee-jerk backlash and demonization" is just not accurate. There is a very well-known counterexample. Researchers identified that the mRNA COVID-19 vaccines were associated with an increased risk of myocarditis, particularly among younger males. This is rare - something like 3 excess cases per 100,000 doses. This has been studied extensively. Regulators required additional surveillance and it's included in all the guidance from regulators and physicians associations. The consensus has been that this is an acceptable risk, particularly since COVID itself is associated with an increased risk of myocarditis. Clearly you have a different view, but the consensus view is based on analyzing data from millions of patients across many countries, not on a "knee-jerk backlash".
> The claim that it is not possible to "question the new mRNA platform publicly without knee-jerk backlash and demonization" is just not accurate
I’m not a Covid truther, anti-vaxxer, or anything of the sort, but let’s be honest here. Mainstream urban society will absolutely attack anyone who doesn’t adhere to the consensus view on covid (among many other topics). It’s an overreaction stemming from years of dealing with bad-faith trolls. But the net result is an enforcement of a specific political orthodoxy.
That was for clinical myocarditis in the overall population, but the rate of subclinical cardiac damage among young males was significantly higher, around 1% with abnormal ECGs post vaccination: https://link.springer.com/article/10.1007/s00431-022-04786-0 .
Exactly this - vaccinate even a small town and cardiovascular issues will start popping amongst the neighbors, there is very good reason why there has been, and is, a public backlash on the MRNA vaccine usage among those who have eyes to see and ears to hear.
In the paper it says 0.1%. " Cardiac symptoms are common after the second dose of BNT162b2 vaccine, but the incidences of significant arrhythmias and myocarditis are only 0.1%." Also note: "subclinical".
"Only"? COVID posed a negligible risk for young males without major preexisting conditions. By contrast, common cardiac symptoms paired alongside significant arrhythmia and myocarditis in 1 in 1000, disproportionately affecting young males, is huge.
And I expect we will eventually come to find out that the overall (particularly longer term) side effects of these drugs have been greatly underestimated. For instance excess mortality continues to remain extremely high [1], even though it would be expected to be negative following a pandemic simply because those most affected by COVID were those already near death. Put more bluntly, disproportionately get rid of the elderly and future death rates should be lower than they would be otherwise. So why are disproportionately large numbers of people continuing to die?
One also needs to understand that myocarditis is not uncommon, and especially common after viral including COVID itself. Also "subclinical" means that this includes mild cases.
Every time I've gotten an MRI the doctors and techs have sworn up and down it's impossible for this stuff to stick around. Getting tired of not being able to believe what doctors say...
That's surprising, it's at least casually known that they're bio accumulative to some extent. I've joked to the techs before about gadolinium eventually accumulating enough to not be necessary if you do it with enough frequency. Realistically though any situation that you're doing the contrast you're probably at a lot more risk of whatever they've found than from the contrast agent.
I had to have contrast to diagnose a simple cyst, which is entirely asymptomatic and was discovered by accident in the background of a cardiac MRI (family history of SCD, but my own heart is fine).
You're making me feel lucky about what was otherwise a very unpleasant experience!
Maybe donate some plasma afterward. There was a study about firefighters exposed to microplastics that had a statistical reduction after regular donations.
> I was kind of annoyed I wasn't offered and MRI, and here we are.
This paper isn’t saying that MRI contrast agent is high risk in general.
There’s a risk in misinterpreting these niche papers to overstate their relative risk. This is a common mistake when people start reading medical papers and begin overweighting the things they’ve read about as the most significant risks.
> I agree. Expecting perfection from humans, even experts, is not reasonable and is frankly counterproductive.
There's a big difference between perfection and "Statistical Literacy Among Doctors Now Lower Than Chance"[1]. I don't think their intentions are bad, but they are woefully incompetent at many basic things.
> There's a big difference between perfection and "Statistical Literacy Among Doctors Now Lower Than Chance"[1]. I don't think their intentions are bad, but they are woefully incompetent at many basic things.
As it happens, the daily practice of medicine does not require interpretation of p-values. Indeed, medicine existed before the p-value.
The people who create studies that ultimately guide policy decisions are specialized (much like people who write GPU drivers are different from those who run inference)
> As it happens, the daily practice of medicine does not require interpretation of p-values. Indeed, medicine existed before the p-value.
What are you talking about? Doctors refer people based on test results every single day. From what I've seen, hardly any of them understand the precision/recall of the tests that they then use to refer you (or not) to screening procedures (which are not all harmless).
What are you talking about? How is a single lab value going to generate a p-value? Why are you presuming that your family med doc should be calculating an ROC for each of her 1,500 patients?
The selection of lab critical values is performed by experts in clinical pathology. Exactly the people who were not included in the paper you cited.
You can find links to support any argument you want on the internet.
To place this in clearer HN terms, you're saying that a front end dev is trash because he didn't write his own web browser in assembly.
To be fair, being knowledgeable about the pre-test probability of a patient having a certain disease vs the sensitivity/specificity of a test IS part of the ideal practice of medicine, although how important it is in practice varies somewhat between specialities. In rheumatology for instance, it is front and center to how you make diagnoses. I was in primary care for a short while myself, and on more than one occasion regretted deeply ordering certain rheumatological screening panels (which you get without asking for it when looking for certain antibodies).
Explaining to a parent the fact that their child did in fact not have a rare, deadly and incurable multi-system disorder even though an antibody which is 98% specific for it showed up on the antibody assay, that we took for an entirely different reason, is the kind of thing thats hard to explain without understanding it yourself.
Bayesian thinking isn’t about p-values and doesn’t need to be presented that way.
If you use the centor criteria before resting for strep, is that worse than getting out a piece of paper and researching background population prevalence?
The OP is being dogmatic about doctors needing to know things he does which is obviously silly.
I can only presume that they got the atomic symbol for potassium (K) mixed up with vitamin K. That’s so wrong it crosses over into being “not even wrong” but entirely wrong and beside the point. I hope they aren’t your doctor anymore, or anyone’s. Please tell me you reported this incident to the state medical board.
Literally every single medical procedure, down to the most mundane, has risks.
That's why we don't give MRI's out the wazoo. We actually gatekeep them a lot, and most research will tell you that investigative MRIs without chief complaints are a bad idea and we don't do them.
I had cancer. I had no MRIs, but multiple CT and PET scans. CT scans and PET scans have risk - they don't just do those for kicks. But you know what else has risks? Cancer. So there's a calculus here.
Every single medical procedure, down to getting your blood drawn, has this calculus. Nothing is risk free.
The data until recently suggested that, so thats the risk you take. Would you rather be living in ancient greece and shoved full of hemlock leaves for arthritis? Or have a 19th century surgeon remove your appendix?
There's risk in life and odds-wise if you're in the developed West, you're going to get care and medicine that will greatly prolong your life.
Also this paper is super vague. What percent of people even get this? How long does it last? They havent even done a study to see how long it lasts yet. I have a feeling this isnt going to be our generation's asbestos or thalidomide.
That being said, you should decide your own risk profile. If MRI gives you concerns there are alternatives that dont involve contrast.
But given our track record, a little humility would go along way.
When a highly educated doctor tells you that something is safe, a person is going to assume that means that someone somewhere has proven that the substance is safe. If what they really mean is that no one really knows, but so far, no experiments have been able to prove danger, then we should say that instead.
> When a highly educated doctor tells you that something is safe, a person is going to assume that means that someone somewhere has proven that the substance is safe.
Contrast agent has been widely studied and determined to be reasonably safe. You’re not going to be administered any routine procedures or compounds that are known to be dangerous without an examination of the risks and benefits.
> If what they really mean is that no one really knows, but so far, no experiments have been able to prove danger, then we should say that instead.
“No experiments have been able to prove danger” is too generic to be usefully different than saying that it’s understood to be reasonably safe.
Even this paper isn’t saying that contrast agent is bad or dangerous in general. It’s exploring a potential effect that we can now detect and study.
Exactly...it's also not reasonable to be asked to prove a negative. "Prove it's safe" (equivalent to "prove there isn't any danger") is "prove there isn't a teapot orbiting Venus" territory.
Every procedure has some negligible risk, and doctors are trained to mitigate major risks to peoples' health with screenings, medications and surgeries that are of lesser risk than the alternative of inaction. "Safe" is a reasonable explanation for the vast majority of laymen they have to communicate with.
My point is not that you must prove it safe. My point is that it is dangerous to communicate to people that something is safe, and simply assume that they understand that negatives can’t be proven, and you don’t literally mean that someone has proven it to be safe.
This is pretty much how we get into the territory of "this product may contain peanuts" even if it has never even been near peanuts, but that warning is need because if in the offcase it has touched peanuts the company can't be sued. But this makes pretty much every other warning worthless.
We shouldn't have to clarify that everything is only 99.999% safe and assume that everything carries some form of risk even if small.
By that standards everything we do is unsafe. Every single activity we do carry some neglible risk. Explaining all of these would be lot more trouble than value in general.
By that definition there is literally no substance in existence that has been proven safe. Because the definition of safe is that no experiments have been able to demonstrate danger.
You know that you can’t prove a negative.
I know that you can’t prove a negative.
Probably most people on HN know that you can’t prove a negative.
But when a person who doesn’t spend their time nerding out on science goes to the doctor and hears, “the substance is safe”, it is not a guarantee that they know that you can’t prove a negative. If you can’t be sure that your audience knows that it’s not possible to prove a negative, then you should be pretty cautious with your words.
Safe, in the context of living on Earth, means an acceptably low risk of a bad outcome.
Tylenol is safe. Tylenol can also permanently damage your kidneys.
Walking is safe. Walking can also permanently damage your cartilage.
Food is safe. Thousands of people die from choking.
We all know this, colloquially. When it comes to medicine, it is as if one's brain hops and skips right out of their ear. It's not magic, it works like everything else on Earth works.
I think there is a non-insignificant number of people who would understand the word safe as no risk, who if something bad happened to them after submitting themselves to such a safe procedure, would find themselves deceived. Technically, I think they would be correct. Therefore, it should be explained that there is a risk but that it is on some order that they can relate to, like the risk of walking down the street.
A doctor will 100% explain that a procedure has a risk. They will say something like this procedure is “generally safe” but there is a very small risk of complications. Then they will make them sign a consent form spelling out those risks.
Yes, exactly, but that is the definition that people who are not doctors are going to use when doctors tell them that something is safe. So we shouldn’t do that.
There is nothing mathematically 100% safe, the human meaning of the word inherently involves some kind of uncertainty.
Going for a test itself via car has a quite significant risk itself, should the doctor say that you shouldn't move out of this room, it's not safe?
Like even regularly used medicine has some slight chance of an adverse reaction, that's how minuscule side effects multiplied to human population times the number it's taken results in.
Guess what often has many orders of magnitude greater risk? Continuing having the disease you went to the doctor with in the first place, or having it lie undiscovered.
Around 10 years ago, I had an brain MRI with contrast. I specifically googled it and found a paper saying it builds up in the brain. I asked the MRI specialist about it, she was surprised I knew this and said she was familiar with the research. She mentioned that her professor also knew about it, but that the paper had other motivations, some conflict of interest, and that I shouldn't be worried. FFS.
Contrast isn't always necessary. Am not a doctor, but I have MS and get them regularly.
I've only had a couple with contrast. My understanding is that contrast highlights abnormal stuff and some tissue sorts more than without contrast. Specifically, they use it in MS to get a better look at an active lesion in the brain. You can still see the lesion without the contrast, though, so most of the MRIs are taken without contrast and then another with contrast if necessary. They have known about various side effects of contrast for some years (allergies, etc).
Thanks - I've put that link in the toptext above. I'm not sure it makes sense to swap out the submitted URL with it. Hopefully people will take a look at both.
You know what other metal stays in the body, permanently bound to bone and other organs? Bismuth, as in bismuth salycilate, aka Peptobismol. A tiny % actually stays in your body.
Does that cause any symptoms? Because apparently this can, and they tell you how to avoid it.
> Lead author Dr Brent Wagner told Newsweek he personally avoids vitamin C when undergoing MRI with contrast, citing its potential to increase gadolinium reactivity. “Metabolic milieu,” including high oxalic acid levels, could explain why some individuals experience severe symptoms while others do not, he said.
Avoiding high-oxalic foods for a few days before the MRI also seems like a good idea. Just check the diet for calcium oxalate kidney stones.
"After ingestion, bismuth is primarily found in trace amounts within organs such as the kidney, liver, spleen, and, in rare cases, the brain, where it accumulates intracellularly—especially in lysosomes and nuclear membranes—and extracellularly in basement membranes of blood vessels.[1-4] In normal therapeutic use, the amount of tissue-bound bismuth is extremely low and is not associated with adverse effects.
Potential consequences of tissue-bound bismuth are generally negligible at standard doses, but chronic or excessive exposure can lead to toxicity, most notably neurotoxicity (bismuth encephalopathy).[1][4-6] In cases of bismuth intoxication, histochemical studies have shown accumulation in neurons and glial cells, particularly in the cerebellum, thalamus, and hippocampus, with clinical manifestations including confusion, myoclonus, and encephalopathy.[1][4-6] However, these effects are reversible upon discontinuation of bismuth exposure, and recovery is typically complete within weeks.[5-6]
Animal studies confirm that bismuth binds to proteins such as ferritin and metallothionein, and is retained in lysosomes, nuclear membranes, and myelin-associated proteins.[2][4][7] The kidney is the primary site of accumulation and excretion, and tissue levels decline after cessation of exposure, with little evidence of permanent retention at therapeutic doses.[2-3]
In summary, permanent tissue binding of bismuth is minimal and clinically insignificant with standard use, but chronic high-dose exposure can result in neurotoxicity and other organ effects, which are reversible after stopping bismuth.[5-6][8-9]"
1.
Autometallographic Tracing of Bismuth in Human Brain Autopsies.
Stoltenberg M, Hogenhuis JA, Hauw JJ, Danscher G.
Journal of Neuropathology and Experimental Neurology. 2001;60(7):705-10. doi:10.1093/jnen/60.7.705.
2.
Metallobiochemistry of Ultratrace Levels of Bismuth in the Rat II. Interaction of Bi With Tissue, Intracellular and Molecular Components.
Sabbioni E, Groppi F, Di Gioacchino M, Petrarca C, Manenti S.
Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). 2021;68:126752. doi:10.1016/j.jtemb.2021.126752.
3.
Distribution of Bismuth in the Rat After Oral Dosing With Ranitidine Bismuth Citrate and Bismuth Subcitrate.
Canena J, Reis J, Pinto AS, et al.
The Journal of Pharmacy and Pharmacology. 1998;50(3):279-83. doi:10.1111/j.2042-7158.1998.tb06861.x.
4.
In Vivo Distribution of Bismuth in the Mouse Brain: Influence of Long-Term Survival and Intracranial Placement on the Uptake and Transport of Bismuth in Neuronal Tissue.
Larsen A, Stoltenberg M, Søndergaard C, Bruhn M, Danscher G.
I think the thing to remember with this, as with any kind of medical procedure, is the benefits versus the risks. In many cases, if you're getting this kind of MRI contrast, there's probably a good reason for it. So even if there's some risk, it might be better than say, the cancer or something else they're looking for. I feel like this is something that's often forgot in these discussions.
My kid went to brain MRI because of migraines (standard procedure here for kids to check if there is e.g. a tumor causing the headache). I was pretty nervous due to this kind of research and the preparatory material saying that they might need to use a contrast agent. In the end they didn’t use a contrast agent and I stressed unnecessarily.
1. The correction doesn’t invalidate that previous study at all
2. I fail to see how the previous study is an “underpinning” of the new paper. The new paper is a chemistry paper about dissociation of GBCAs in the presence of certain chemicals. Maybe people care because it is a potential explanation for toxicity, but the paper is very focused on the chemistry findings.
It is underpinning, as it is the most frequently cited in the entire paper.
It is underpinning, as the claims in both introduction and conclusion are precipitate to it.
The correction:
> After personal communication with the radiologists the administered Gd-contained contrast agent was documented in the MR examination reports of the mentioned nine patients incompletely and inexactly as Gd–DTPA by themselves. There is solely one MR contrast agent used in the described observation period: Gd–DTPA–BMA. Therefore, all mentioned nine patients received Gd–DTPA–BMA and not Gd–DTPA.
Means that Gd-DTPA is irrelevant. Guess which is analysed here?
I’m not a specialist so I can’t comment on how significant that is.
We generally don’t use the compounds that cause NSF, which is one reason why the 2006 paper link you provided may not reflect the agents under current study.
Yes. The problem is that it's common in the industry. But it's ultimately up to the patient. Maybe alone. Pretty much guaranteed scared. Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress.
What are you proposing instead? Should patients just die of their illness instead?
Medical procedures have risk, some are small risk some are higher risk. There are none that are 100% safe. Doctors are supposed to evaluate if the risk is worth the value the procedure would supply.
What is the alternative to the status quo that you would propose?
During COVID people were losing their minds about one in a million chance of complications caused by vaccination. I did some research (but actually), and found that that’s comparable to the rate of complications for any use of an injected drug or even saline. Just piercing the skin with a tiny needle is a “medical procedure” with a non-zero risk, especially in the elderly and the immunocompromised.
I had a couple of MRIs recently and got curious about gadolinium contrast. Again, there is a non-zero risk, but if you eliminate the cohort with reduced kidney function and those getting regular repeated MRIs, the risk is comparable to the use of an I/V, which is how it’s administered.
The only thing that upset me was that the staff didn’t ask me verbally about kidney issues to double-check. They also didn’t remind me to drink a bunch of water to flush it out of my system. (Some articles recommend administering a diuretic.)
For that matter they didn’t check me properly form metal fragments either!
Similarly, I’ve had vaccinations administered where I had to remind the doctor to clean the area with alcohol first and to tap the syringe to get rid of the bubbles.
Bad procedures are more dangerous than the drugs being administered!
The risk with gadolinium is that it is never fully removed from your system and if you are allergic to it, it means a PERMANENT whole body allergic reaction. Skin itching and incurable chronic pain. It has nothing to do with kidney function.
I got familliar with this condition by a random persons blog who go affected by this during normal MRI and also didn't expect to be part of 1-2%. Unfortunately the blog is now gone, and that post now only lives inside my RSS reader.
Well no one should get MRIs with contrast for fun. Moreover, doctors regularly use contrast off label.
My dad was in this industry when nsf first came out. We would be dragged along to after hours family things at conferences. Doctors openly said they gave contrast off label at dosages not approved by the FDA for organ systems not approved by the Fda. Even children. I'm sure they had their reasons, but I'm also sure they never disclosed the possibility of nsf and just told parents their kids needed it, because they admitted it.
There's a big difference between not getting the MRI and getting the MRI without gadolinium. My suggestion is to ensure that people know the risks outside of just the people who work in it. I'm not sure how that didn't get across in my original comment. With your comprehension skills, you are at an increased risk of falling victim to this exact scenario
My understanding was that gadolinium was already only used in cases where a normal MRI would be ineffective.
I don't know how the risk is actually communicated to patients. I imagine it varries by country. However, normal medical ethics would be to explain risks to the patients. Is there a reason to believe that isn't happening?
There’s really a risk vs benefit. If you have a brain tumour you need contrast to assess the type of tumour, its growth, if it’s a glioma whether it’s transformed and so on. If someone is being given contrast it is going to change their clinical management.
It seems an odd fixation of just MR contrast when the same could be said of all drugs. Does your doctor/surgeon go into the minutiae of all drugs and possible consequences? By this line of thinking, saline is not without risks, should they go into depth about that?
People already poorly retain information or even comprehend it at appointments or interventions, is there any point adding more burden onto their attendances?
Nobody explains shit like this. They will turn down the risks because if they were honest, most wouldn't accept that risk. Because the risk is PERMANENT life changing condition.
>>> Yes. The problem is that it's common in the industry. But it's ultimately up to the patient. Maybe alone. Pretty much guaranteed scared. Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress.
> There's a big difference between not getting the MRI and getting the MRI without gadolinium. My suggestion is to ensure that people know the risks outside of just the people who work in it. I'm not sure how that didn't get across in my original comment. With your comprehension skills, you are at an increased risk of falling victim to this exact scenario
I don't see anything wrong with the GP's comprehension skills.
Anyway, every procedure has risk - and no procedure is recommended if there is not an offsetting clinical benefit. There are clear guidelines for when gadolinium is to be used for an MRI and the guidelines factor in risk for 'NSF'.
When I had mine I got the form with warnings about side effects. When I saw the allergic reaction I was a bit concerned, I asked the tech and was told it wasn't a big deal. Since I was in the basement I didn't have service and I decided to trust them given the large number of my friends who've had MRIs. It was fine, but it seemed like a major thing to toss in the patients lap right before they get strapped down in a tube.
But there’s a potential risk of an allergic reaction to any drug you take, any food or drink you consume, even environmental substances - perfumes; hayfever is an allergic reaction to pollens. You don’t know you have one until you have the reaction. I didn’t know I was allergic to penicillins until I needed them for an infection and it turns out I am.
People getting MRIs frequently have bigger fish to fry.
When my wife was under cancer treatment she had them frequently. Risking some minor reaction, which in her case was disclosed many times, was well worth the value in managing the acute and long term treatment plan.
> Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress
I was never communicated about gadolinium pollution. Not once.
And yes, on my recent MRI, I explicitly asked why there was metal particulate in my joint. "I dont know, sometimes it happens'... No you fucking tool of a doctor. Its gadolinium.
Are you certain it is gadolinium? As I recall from a family member's health issues you can get particulates in joints from arthroscopic surgery or from the metal implants. Not saying that is what happened in your case, but I'm just curious because I remember reading about metal in joints as a potential side effect of the surgery.
I find it odd that when I happen across an article talking about some negative links between x and y being discovered, there's always someone in the comments saying this was known for some decades.
As someone with CKD and scheduled for an MRI, this was anxiety-inducing.
The Cleveland Clinic has a good overview[1]. Since there have been no reports of NSF in 15 years, I don't think it's rational to avoid MRIs based on gadolinium retention concerns.
Note that MRI with contrast has very low risk and I am not aware of any evidence that Gadolinium retention even has adverse health effects. It is a concern though and this is why it is being studied. But I do not think the use of MRI contrast agents is something anybody without kidney disease should be concerned about. In general, risks and benefits must be balanced for any medical procedure. Such risks are continuously monitored and studied and guidelines are formulated based on this. Also consider that there is very clear harm from people being scared away by misinformation from medical procedures they would benefit from.
> Nobody told me gadolinium can be retained before I had it the first couple times.
The reason these publications exist is that this is new knowledge
> Like somebody else mentioned, they swore up and down it's perfectly safe.
I am positive that you were not told that '[gadolinium] is perfectly safe' because there is a well-known complication of gadolinium administration. It's rare, but it's mentioned in every consent form.
> I am positive that you were not told that '[gadolinium] is perfectly safe' because there is a well-known complication of gadolinium administration. It's rare, but it's mentioned in every consent form.
Consent is not "Sign this cause its the only course of treatment". And thats what happens almost every time.
And yes, I too have gadolinium retention in my joint. 3 MRIs. And no, was not told this was a complication... But I'm sure the papers I signed included weasel words to that effect.
> And yes, I too have gadolinium retention in my joint. 3 MRIs. And no, was not told this was a complication... But I'm sure the papers I signed included weasel words to that effect.
The presence of the gadolinium is not a complication. At best, it is an unintended side effect whose clinical significance is not known.
A complication is an unexpected/non-routine, negative outcome. We now have learned that the deposition is something to expect. There is no new information around clinical changes that one can attribute to gadolinium.
I think you must have misunderstood where the artifact was coming from. Gadolinium retention has been shown to occur, but has not been reliably linked to any clinical symptoms. Gadolinium tissue retention also does not interfere in interpretation.
There are risks with every procedure and medication.
A dose of ibuprofen could give you Stevens–Johnson syndrome or TENS and you end up in a burn war for months.
Patients should be made aware of all the risks for any treatment, but it would be impossible to avoid they edge cases even with relatively basic medical care.
Most people lack the medical literacy to understand any of this. People don’t read their letters telling them to not eat before surgery, are they going to read the list of potential side effects of a medication? How many people read the information sheets that come with their prescription medication?
Great. Only this year, I got roughly 6 doses of gadlinium, and prior to that, I got one every year, going back 20 years. I just recently chatted with a MRI nurse about the fact that I have a bad feeling about getting that stuff so frequently over time, and she dismissed my concerns. They used to remind patients to drink more after the MRI, but even that routine has been ended roughly 5 years ago. Is there anything else I can do except drink more on the day of the injection?
This is very interesting to see on here. My mother was the dissenting vote on an FDA panel on this. There are articles about it. I'll copy her words (as reported by something but seems legit)
> She said that the FDA's plan doesn't go far enough.
> "It's hard to dismiss an anecdotal report when you are the anecdote. When a patient is finally tested and found to have gadolinium retention, there's no FDA-approved antidote. So what does the patient do?"
And I want to reiterate that she was "the" no not "a" no. I don't know if her vote alone is what's caused more research into this. But it's probably the thing I brag about her the most. Even though everybody else said it was fine or abstained, she stood strong. If you look up the articles from the time of the panel (2017) you'll see a lot of articles about this panel and how she was the sole no vote. Included in that was a public post from Chuck Norris praising her. He was going to come out to meet us but I think it was a bad Texas hurricane season so that fell through
In case anyone is wondering what Chuck Norris has to do with all this:
> Chuck and Gena Norris filed a lawsuit against several medical companies in 2017, alleging that a gadolinium-based contrast agent used in Gena Norris's MRIs caused her to develop a condition called gadolinium deposition disease and resulted in debilitating symptoms like cognitive issues, pain, and muscle wasting. In January 2020, the Norrises, along with their attorneys, voluntarily dismissed the lawsuit with prejudice, meaning it cannot be refiled. The dismissal was made without a settlement payment, and each party paid their own legal costs.
It might give a glimpse into his worldview to mention that during the COVID pandemic Mr Norris shared an article on social media that claimed that the COVID vaccinations killed millions of people. [0]
[0] https://m.facebook.com/story.php?story_fbid=870953857718632&...
His reaction is kind of the essence of populist backlash.
People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the experts are human, fallible, and sometimes incompetent or corrupt.
Since the original message was one of unqualified absolute faith in the experts, the backlash is to flip over to believing that the experts are satan incarnate and pure evil and always wrong.
It reminds me psychologically of the arc of an immature relationship. First they’re perfect, everything about them is perfect, they’re going to be your soul mate forever. Then you catch them in a lie or they do something embarrassing. Then you get the screaming breakup. Everything about them is the worst now and you never want to see them again.
A large portion humanity seem incapable of embracing uncertainty and nuance and are over eager to embrace whoever is willing to peddle certainty and simplicity.
As long as that is true it seem naive to believe that nuanced institutions can exist as dominant entities in human societies.
This is true, but it is also true that "official" communication often tends to project level of certainty that just does not correspond to the actual level of knowledge, and Covid was pretty bad in this regard, because in absence of actual knowledge, hard recommendations were being issued to people.
Saying sincerely "we are not yet sure if Covid spreads by touching surfaces" etc. would have gone a long way.
I am not even touching the dirty topic of "practise societal distancing unless you go to an anti-racist demonstration, because racism is worse than Covid". That alone probably sunk the levels of trust for a generation in the US, especially among people right of the center. Politicizing science is suicidal.
Back to normal uncertainty. It was the same with various dietary recommendations. Older people remember several major overhauls thereof (are eggs fine or not, and in which amount?), and again, these were presented with a level of certainty that does not correspond to the actual - somewhat fuzzy - state of nutritional science.
You can only do this so long before unleashing an epidemics of distrust.
> Saying sincerely "we are not yet sure if Covid spreads by touching surfaces" etc. would have gone a long
It wouldn't have, uncertainty creates general panic as well, that soon turns into disarray of chaotic recommendations among the masses.
IMHO, "short term uncertainty" > "long term distrust".
I don't like the "common people are too stupid to be told the truth" attitude (which includes uncertainities).
It is both too smug to work, and unworkable in today's networked world, where those same people will notice really fast that someone is treating them like idiots, and react with resentment and loss of trust.
That is the new enlightennents main project, researching these retardations, building societal implants to overcone or at least life with them. Handling the eldritch horror moments where we can not or the handicaps are societal load bearing and future crippling. The faces they make when the dog dies you can not unsee.
> People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the experts are human, fallible, and sometimes incompetent or corrupt.
Try
People are told that the authorities have it all under control and the experts can be trusted. Then they discover that the authorities and experts, in the name of “the greater good”, actively suppressed debate, knowingly mis-represented uncertainties, pretended reports of serious adverse reactions to vaccination were not only impossible but simply fear-mongering from the uneducated, and then pressured social-media platforms to take down factual information when it threatened the official narrative.
This without even touching on the fact that the WHO, who has one damned job, refused to even declare a pandemic and spoke against any travel restrictions or public health measures outside their lazy guidance until the virus was confirmed to be spreading out of control in nearly every nation on earth.
Having lived through this, observed it first-hand, read the studies, having dozens of anecdotal evidence on top from near friends and family, and still not able to even question the new mRNA platform publicly without knee-jerk backlash and demonisation, has done more damage to my faith in institutions and the medical community than anything else I’ve witnessed in my near forty years on this planet. Covid made crystal clear to me that we still live under tyrannical dogmatic rule devoid of scientific nuance because it’s “for the greater good”.
The claim that it is not possible to "question the new mRNA platform publicly without knee-jerk backlash and demonization" is just not accurate. There is a very well-known counterexample. Researchers identified that the mRNA COVID-19 vaccines were associated with an increased risk of myocarditis, particularly among younger males. This is rare - something like 3 excess cases per 100,000 doses. This has been studied extensively. Regulators required additional surveillance and it's included in all the guidance from regulators and physicians associations. The consensus has been that this is an acceptable risk, particularly since COVID itself is associated with an increased risk of myocarditis. Clearly you have a different view, but the consensus view is based on analyzing data from millions of patients across many countries, not on a "knee-jerk backlash".
> The claim that it is not possible to "question the new mRNA platform publicly without knee-jerk backlash and demonization" is just not accurate
I’m not a Covid truther, anti-vaxxer, or anything of the sort, but let’s be honest here. Mainstream urban society will absolutely attack anyone who doesn’t adhere to the consensus view on covid (among many other topics). It’s an overreaction stemming from years of dealing with bad-faith trolls. But the net result is an enforcement of a specific political orthodoxy.
>something like 3 excess cases per 100,000 doses
That was for clinical myocarditis in the overall population, but the rate of subclinical cardiac damage among young males was significantly higher, around 1% with abnormal ECGs post vaccination: https://link.springer.com/article/10.1007/s00431-022-04786-0 .
Exactly this - vaccinate even a small town and cardiovascular issues will start popping amongst the neighbors, there is very good reason why there has been, and is, a public backlash on the MRNA vaccine usage among those who have eyes to see and ears to hear.
Please do not spread misinformation. Nobody expects "cardiovascular issues" "popping amongst the neighbors" and there is no evidence supporting this.
In the paper it says 0.1%. " Cardiac symptoms are common after the second dose of BNT162b2 vaccine, but the incidences of significant arrhythmias and myocarditis are only 0.1%." Also note: "subclinical".
"Only"? COVID posed a negligible risk for young males without major preexisting conditions. By contrast, common cardiac symptoms paired alongside significant arrhythmia and myocarditis in 1 in 1000, disproportionately affecting young males, is huge.
And I expect we will eventually come to find out that the overall (particularly longer term) side effects of these drugs have been greatly underestimated. For instance excess mortality continues to remain extremely high [1], even though it would be expected to be negative following a pandemic simply because those most affected by COVID were those already near death. Put more bluntly, disproportionately get rid of the elderly and future death rates should be lower than they would be otherwise. So why are disproportionately large numbers of people continuing to die?
[1] - https://ourworldindata.org/grapher/excess-mortality-p-scores...
You may want to look at this paper to get a better idea of risk and benefits, e.g. Fig 2 and Fig 3: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA....
One also needs to understand that myocarditis is not uncommon, and especially common after viral including COVID itself. Also "subclinical" means that this includes mild cases.
Wow, for once Chuck didn't win
I mean there have been no reported cases of NSF in the last ten years after certain gadolinium agents were removed from the market.
Every time I've gotten an MRI the doctors and techs have sworn up and down it's impossible for this stuff to stick around. Getting tired of not being able to believe what doctors say...
That's surprising, it's at least casually known that they're bio accumulative to some extent. I've joked to the techs before about gadolinium eventually accumulating enough to not be necessary if you do it with enough frequency. Realistically though any situation that you're doing the contrast you're probably at a lot more risk of whatever they've found than from the contrast agent.
I had to have contrast to diagnose a simple cyst, which is entirely asymptomatic and was discovered by accident in the background of a cardiac MRI (family history of SCD, but my own heart is fine).
You're making me feel lucky about what was otherwise a very unpleasant experience!
Maybe donate some plasma afterward. There was a study about firefighters exposed to microplastics that had a statistical reduction after regular donations.
Pretty much just diluting it out of your system.
Materials like these accumulate in other parts of your body, like bones. Letting some blood out is not gonna change it.
Nah, they used it on me when I cracked a toe. If I knew that this may be that dangerous I’d go the way without the contrast agent.
The other day I had to get a CT scan, I was kind of annoyed I wasn't offered and MRI, and here we are.
I hold a different opinion to you though, I'm glad doctors are always learning more while generally operating with good /extremely good intentions.
> I was kind of annoyed I wasn't offered and MRI, and here we are.
This paper isn’t saying that MRI contrast agent is high risk in general.
There’s a risk in misinterpreting these niche papers to overstate their relative risk. This is a common mistake when people start reading medical papers and begin overweighting the things they’ve read about as the most significant risks.
Really wish more people had that mind set. Practicing medicine isn't easy, especially in the US when you have to battle the insane insurance industry.
> I hold a different opinion to you though, I'm glad doctors are always learning more while generally operating with good /extremely good intentions.
I agree. Expecting perfection from humans, even experts, is not reasonable and is frankly counterproductive.
Willful ignorance is one thing, but people who genuinely attempt to do the right thing at worst just need to be steered slightly differently.
expecting humbleness and willingness to be wrong from medical personnel is reasonably though
> I agree. Expecting perfection from humans, even experts, is not reasonable and is frankly counterproductive.
There's a big difference between perfection and "Statistical Literacy Among Doctors Now Lower Than Chance"[1]. I don't think their intentions are bad, but they are woefully incompetent at many basic things.
[1] https://slatestarcodex.com/2013/12/17/statistical-literacy-a...
> There's a big difference between perfection and "Statistical Literacy Among Doctors Now Lower Than Chance"[1]. I don't think their intentions are bad, but they are woefully incompetent at many basic things.
As it happens, the daily practice of medicine does not require interpretation of p-values. Indeed, medicine existed before the p-value.
The people who create studies that ultimately guide policy decisions are specialized (much like people who write GPU drivers are different from those who run inference)
> As it happens, the daily practice of medicine does not require interpretation of p-values. Indeed, medicine existed before the p-value.
What are you talking about? Doctors refer people based on test results every single day. From what I've seen, hardly any of them understand the precision/recall of the tests that they then use to refer you (or not) to screening procedures (which are not all harmless).
> What are you talking about?
What are you talking about? How is a single lab value going to generate a p-value? Why are you presuming that your family med doc should be calculating an ROC for each of her 1,500 patients?
The selection of lab critical values is performed by experts in clinical pathology. Exactly the people who were not included in the paper you cited.
You can find links to support any argument you want on the internet.
To place this in clearer HN terms, you're saying that a front end dev is trash because he didn't write his own web browser in assembly.
To be fair, being knowledgeable about the pre-test probability of a patient having a certain disease vs the sensitivity/specificity of a test IS part of the ideal practice of medicine, although how important it is in practice varies somewhat between specialities. In rheumatology for instance, it is front and center to how you make diagnoses. I was in primary care for a short while myself, and on more than one occasion regretted deeply ordering certain rheumatological screening panels (which you get without asking for it when looking for certain antibodies).
Explaining to a parent the fact that their child did in fact not have a rare, deadly and incurable multi-system disorder even though an antibody which is 98% specific for it showed up on the antibody assay, that we took for an entirely different reason, is the kind of thing thats hard to explain without understanding it yourself.
Bayesian thinking isn’t about p-values and doesn’t need to be presented that way.
If you use the centor criteria before resting for strep, is that worse than getting out a piece of paper and researching background population prevalence?
The OP is being dogmatic about doctors needing to know things he does which is obviously silly.
Except that a disturbing number of doctors insist that they are always right and you are always wrong.
A year ago, one insisted vehemently—to the point of yelling—that I shouldn't be supplementing Vitamin K because my potassium levels were fine.
As opposed to what group of humans?
I can only presume that they got the atomic symbol for potassium (K) mixed up with vitamin K. That’s so wrong it crosses over into being “not even wrong” but entirely wrong and beside the point. I hope they aren’t your doctor anymore, or anyone’s. Please tell me you reported this incident to the state medical board.
https://en.wikipedia.org/wiki/Not_even_wrong
> "What you said was so confused that one could not tell whether it was nonsense or not."
Literally every single medical procedure, down to the most mundane, has risks.
That's why we don't give MRI's out the wazoo. We actually gatekeep them a lot, and most research will tell you that investigative MRIs without chief complaints are a bad idea and we don't do them.
I had cancer. I had no MRIs, but multiple CT and PET scans. CT scans and PET scans have risk - they don't just do those for kicks. But you know what else has risks? Cancer. So there's a calculus here.
Every single medical procedure, down to getting your blood drawn, has this calculus. Nothing is risk free.
> That's why we don't give MRI's out the wazoo
Why? What are the risks of MRIs without contrast?
MRIs involve very powerful magnets and inattention around them has led to several widely-publicized deaths.
They’re also loud and can give patients a sense of claustrophobia or panic.
The reason is cost and availability, not risk.
Which country do you live in?
Here in Germany you have to sign something if they give you "stuff" informing you of possible risks. Something that always exists.
The data until recently suggested that, so thats the risk you take. Would you rather be living in ancient greece and shoved full of hemlock leaves for arthritis? Or have a 19th century surgeon remove your appendix?
There's risk in life and odds-wise if you're in the developed West, you're going to get care and medicine that will greatly prolong your life.
Also this paper is super vague. What percent of people even get this? How long does it last? They havent even done a study to see how long it lasts yet. I have a feeling this isnt going to be our generation's asbestos or thalidomide.
That being said, you should decide your own risk profile. If MRI gives you concerns there are alternatives that dont involve contrast.
No one is asking to go back to Ancient Greece.
But given our track record, a little humility would go along way.
When a highly educated doctor tells you that something is safe, a person is going to assume that means that someone somewhere has proven that the substance is safe. If what they really mean is that no one really knows, but so far, no experiments have been able to prove danger, then we should say that instead.
> When a highly educated doctor tells you that something is safe, a person is going to assume that means that someone somewhere has proven that the substance is safe.
Contrast agent has been widely studied and determined to be reasonably safe. You’re not going to be administered any routine procedures or compounds that are known to be dangerous without an examination of the risks and benefits.
> If what they really mean is that no one really knows, but so far, no experiments have been able to prove danger, then we should say that instead.
“No experiments have been able to prove danger” is too generic to be usefully different than saying that it’s understood to be reasonably safe.
Even this paper isn’t saying that contrast agent is bad or dangerous in general. It’s exploring a potential effect that we can now detect and study.
Exactly...it's also not reasonable to be asked to prove a negative. "Prove it's safe" (equivalent to "prove there isn't any danger") is "prove there isn't a teapot orbiting Venus" territory.
Every procedure has some negligible risk, and doctors are trained to mitigate major risks to peoples' health with screenings, medications and surgeries that are of lesser risk than the alternative of inaction. "Safe" is a reasonable explanation for the vast majority of laymen they have to communicate with.
My point is not that you must prove it safe. My point is that it is dangerous to communicate to people that something is safe, and simply assume that they understand that negatives can’t be proven, and you don’t literally mean that someone has proven it to be safe.
This is pretty much how we get into the territory of "this product may contain peanuts" even if it has never even been near peanuts, but that warning is need because if in the offcase it has touched peanuts the company can't be sued. But this makes pretty much every other warning worthless.
We shouldn't have to clarify that everything is only 99.999% safe and assume that everything carries some form of risk even if small.
By that standards everything we do is unsafe. Every single activity we do carry some neglible risk. Explaining all of these would be lot more trouble than value in general.
By that definition there is literally no substance in existence that has been proven safe. Because the definition of safe is that no experiments have been able to demonstrate danger.
You can’t prove a negative.
You know that you can’t prove a negative. I know that you can’t prove a negative. Probably most people on HN know that you can’t prove a negative.
But when a person who doesn’t spend their time nerding out on science goes to the doctor and hears, “the substance is safe”, it is not a guarantee that they know that you can’t prove a negative. If you can’t be sure that your audience knows that it’s not possible to prove a negative, then you should be pretty cautious with your words.
Safe, in the context of living on Earth, means an acceptably low risk of a bad outcome.
Tylenol is safe. Tylenol can also permanently damage your kidneys.
Walking is safe. Walking can also permanently damage your cartilage.
Food is safe. Thousands of people die from choking.
We all know this, colloquially. When it comes to medicine, it is as if one's brain hops and skips right out of their ear. It's not magic, it works like everything else on Earth works.
I think there is a non-insignificant number of people who would understand the word safe as no risk, who if something bad happened to them after submitting themselves to such a safe procedure, would find themselves deceived. Technically, I think they would be correct. Therefore, it should be explained that there is a risk but that it is on some order that they can relate to, like the risk of walking down the street.
A doctor will 100% explain that a procedure has a risk. They will say something like this procedure is “generally safe” but there is a very small risk of complications. Then they will make them sign a consent form spelling out those risks.
By that definition, nobody knows anything is safe.
Yes, exactly, but that is the definition that people who are not doctors are going to use when doctors tell them that something is safe. So we shouldn’t do that.
Nobody has proven that not taking an action is safe.
There is nothing mathematically 100% safe, the human meaning of the word inherently involves some kind of uncertainty.
Going for a test itself via car has a quite significant risk itself, should the doctor say that you shouldn't move out of this room, it's not safe?
Like even regularly used medicine has some slight chance of an adverse reaction, that's how minuscule side effects multiplied to human population times the number it's taken results in.
Guess what often has many orders of magnitude greater risk? Continuing having the disease you went to the doctor with in the first place, or having it lie undiscovered.
Around 10 years ago, I had an brain MRI with contrast. I specifically googled it and found a paper saying it builds up in the brain. I asked the MRI specialist about it, she was surprised I knew this and said she was familiar with the research. She mentioned that her professor also knew about it, but that the paper had other motivations, some conflict of interest, and that I shouldn't be worried. FFS.
Why did you have a brain MRI with contrast?
Contrast isn't always necessary. Am not a doctor, but I have MS and get them regularly.
I've only had a couple with contrast. My understanding is that contrast highlights abnormal stuff and some tissue sorts more than without contrast. Specifically, they use it in MS to get a better look at an active lesion in the brain. You can still see the lesion without the contrast, though, so most of the MRIs are taken without contrast and then another with contrast if necessary. They have known about various side effects of contrast for some years (allergies, etc).
This is a poor explanation of an older publication, when the actual new work has a good description:
https://www.frontiersin.org/journals/toxicology/articles/10....
Thanks - I've put that link in the toptext above. I'm not sure it makes sense to swap out the submitted URL with it. Hopefully people will take a look at both.
You know what other metal stays in the body, permanently bound to bone and other organs? Bismuth, as in bismuth salycilate, aka Peptobismol. A tiny % actually stays in your body.
Does that cause any symptoms? Because apparently this can, and they tell you how to avoid it.
> Lead author Dr Brent Wagner told Newsweek he personally avoids vitamin C when undergoing MRI with contrast, citing its potential to increase gadolinium reactivity. “Metabolic milieu,” including high oxalic acid levels, could explain why some individuals experience severe symptoms while others do not, he said.
Avoiding high-oxalic foods for a few days before the MRI also seems like a good idea. Just check the diet for calcium oxalate kidney stones.
> Does that cause any symptoms?
Tinnitus.
Actually, that's the salicylate portion causing tinnitus, not the bismuth.
Can you please share more?
From OpenEvidence.com:
"After ingestion, bismuth is primarily found in trace amounts within organs such as the kidney, liver, spleen, and, in rare cases, the brain, where it accumulates intracellularly—especially in lysosomes and nuclear membranes—and extracellularly in basement membranes of blood vessels.[1-4] In normal therapeutic use, the amount of tissue-bound bismuth is extremely low and is not associated with adverse effects. Potential consequences of tissue-bound bismuth are generally negligible at standard doses, but chronic or excessive exposure can lead to toxicity, most notably neurotoxicity (bismuth encephalopathy).[1][4-6] In cases of bismuth intoxication, histochemical studies have shown accumulation in neurons and glial cells, particularly in the cerebellum, thalamus, and hippocampus, with clinical manifestations including confusion, myoclonus, and encephalopathy.[1][4-6] However, these effects are reversible upon discontinuation of bismuth exposure, and recovery is typically complete within weeks.[5-6] Animal studies confirm that bismuth binds to proteins such as ferritin and metallothionein, and is retained in lysosomes, nuclear membranes, and myelin-associated proteins.[2][4][7] The kidney is the primary site of accumulation and excretion, and tissue levels decline after cessation of exposure, with little evidence of permanent retention at therapeutic doses.[2-3] In summary, permanent tissue binding of bismuth is minimal and clinically insignificant with standard use, but chronic high-dose exposure can result in neurotoxicity and other organ effects, which are reversible after stopping bismuth.[5-6][8-9]"
1. Autometallographic Tracing of Bismuth in Human Brain Autopsies. Stoltenberg M, Hogenhuis JA, Hauw JJ, Danscher G.
Journal of Neuropathology and Experimental Neurology. 2001;60(7):705-10. doi:10.1093/jnen/60.7.705.
2. Metallobiochemistry of Ultratrace Levels of Bismuth in the Rat II. Interaction of Bi With Tissue, Intracellular and Molecular Components. Sabbioni E, Groppi F, Di Gioacchino M, Petrarca C, Manenti S.
Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). 2021;68:126752. doi:10.1016/j.jtemb.2021.126752.
3. Distribution of Bismuth in the Rat After Oral Dosing With Ranitidine Bismuth Citrate and Bismuth Subcitrate. Canena J, Reis J, Pinto AS, et al.
The Journal of Pharmacy and Pharmacology. 1998;50(3):279-83. doi:10.1111/j.2042-7158.1998.tb06861.x.
4. In Vivo Distribution of Bismuth in the Mouse Brain: Influence of Long-Term Survival and Intracranial Placement on the Uptake and Transport of Bismuth in Neuronal Tissue. Larsen A, Stoltenberg M, Søndergaard C, Bruhn M, Danscher G.
Basic & Clinical Pharmacology & Toxicology. 2005;97(3):188-96. doi:10.1111/j.1742-7843.2005.pto_973132.x.
5. Bismuth Encephalopathy- A Rare Complication of Long-Standing Use of Bismuth Subsalicylate. Borbinha C, Serrazina F, Salavisa M, Viana-Baptista M.
BMC Neurology. 2019;19(1):212. doi:10.1186/s12883-019-1437-9.
6. Bismuth Subgallate Toxicity in the Age of Online Supplement Use. Sampognaro P, Vo KT, Richie M, Blanc PD, Keenan K.
The Neurologist. 2017;22(6):237-240. doi:10.1097/NRL.0000000000000144.
7. Bismuth Tracing in Organotypic Cultures of Rat Hippocampus. Locht LJ, Munkøe L, Stoltenberg M.
Journal of Neuroscience Methods. 2002;115(1):77-83. doi:10.1016/s0165-0270(02)00004-3.
8. Bioactive Bismuth Compounds: Is Their Toxicity a Barrier to Therapeutic Use?. Gonçalves Â, Matias M, Salvador JAR, Silvestre S.
International Journal of Molecular Sciences. 2024;25(3):1600. doi:10.3390/ijms25031600.
9. Review Article: Safety of Bismuth in the Treatment of Gastrointestinal Diseases. Tillman LA, Drake FM, Dixon JS, Wood JR.
Alimentary Pharmacology & Therapeutics. 1996;10(4):459-67. doi:10.1046/j.1365-2036.1996.22163000.x.
I think the thing to remember with this, as with any kind of medical procedure, is the benefits versus the risks. In many cases, if you're getting this kind of MRI contrast, there's probably a good reason for it. So even if there's some risk, it might be better than say, the cancer or something else they're looking for. I feel like this is something that's often forgot in these discussions.
My kid went to brain MRI because of migraines (standard procedure here for kids to check if there is e.g. a tumor causing the headache). I was pretty nervous due to this kind of research and the preparatory material saying that they might need to use a contrast agent. In the end they didn’t use a contrast agent and I stressed unnecessarily.
Or to not click through multiple layers of clickbait: https://doi.org/10.1016/j.mri.2025.110383
Unfortunately, the article isn't much better. It has as an underpinning, a corrected paper: https://doi.org/10.1093/ndt/gfl294
1. The correction doesn’t invalidate that previous study at all
2. I fail to see how the previous study is an “underpinning” of the new paper. The new paper is a chemistry paper about dissociation of GBCAs in the presence of certain chemicals. Maybe people care because it is a potential explanation for toxicity, but the paper is very focused on the chemistry findings.
It is underpinning, as it is the most frequently cited in the entire paper.
It is underpinning, as the claims in both introduction and conclusion are precipitate to it.
The correction:
> After personal communication with the radiologists the administered Gd-contained contrast agent was documented in the MR examination reports of the mentioned nine patients incompletely and inexactly as Gd–DTPA by themselves. There is solely one MR contrast agent used in the described observation period: Gd–DTPA–BMA. Therefore, all mentioned nine patients received Gd–DTPA–BMA and not Gd–DTPA.
Means that Gd-DTPA is irrelevant. Guess which is analysed here?
Neither - the OP paper talks about Gd-DOTA.
I’m not a specialist so I can’t comment on how significant that is.
We generally don’t use the compounds that cause NSF, which is one reason why the 2006 paper link you provided may not reflect the agents under current study.
The link between NSF and gadolinium-based agents has been known for almost two decades and is common knowledge in the industry.
Yes. The problem is that it's common in the industry. But it's ultimately up to the patient. Maybe alone. Pretty much guaranteed scared. Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress.
What are you proposing instead? Should patients just die of their illness instead?
Medical procedures have risk, some are small risk some are higher risk. There are none that are 100% safe. Doctors are supposed to evaluate if the risk is worth the value the procedure would supply.
What is the alternative to the status quo that you would propose?
During COVID people were losing their minds about one in a million chance of complications caused by vaccination. I did some research (but actually), and found that that’s comparable to the rate of complications for any use of an injected drug or even saline. Just piercing the skin with a tiny needle is a “medical procedure” with a non-zero risk, especially in the elderly and the immunocompromised.
I had a couple of MRIs recently and got curious about gadolinium contrast. Again, there is a non-zero risk, but if you eliminate the cohort with reduced kidney function and those getting regular repeated MRIs, the risk is comparable to the use of an I/V, which is how it’s administered.
The only thing that upset me was that the staff didn’t ask me verbally about kidney issues to double-check. They also didn’t remind me to drink a bunch of water to flush it out of my system. (Some articles recommend administering a diuretic.)
For that matter they didn’t check me properly form metal fragments either!
Similarly, I’ve had vaccinations administered where I had to remind the doctor to clean the area with alcohol first and to tap the syringe to get rid of the bubbles.
Bad procedures are more dangerous than the drugs being administered!
The risk with gadolinium is that it is never fully removed from your system and if you are allergic to it, it means a PERMANENT whole body allergic reaction. Skin itching and incurable chronic pain. It has nothing to do with kidney function.
I got familliar with this condition by a random persons blog who go affected by this during normal MRI and also didn't expect to be part of 1-2%. Unfortunately the blog is now gone, and that post now only lives inside my RSS reader.
Well no one should get MRIs with contrast for fun. Moreover, doctors regularly use contrast off label.
My dad was in this industry when nsf first came out. We would be dragged along to after hours family things at conferences. Doctors openly said they gave contrast off label at dosages not approved by the FDA for organ systems not approved by the Fda. Even children. I'm sure they had their reasons, but I'm also sure they never disclosed the possibility of nsf and just told parents their kids needed it, because they admitted it.
There's a big difference between not getting the MRI and getting the MRI without gadolinium. My suggestion is to ensure that people know the risks outside of just the people who work in it. I'm not sure how that didn't get across in my original comment. With your comprehension skills, you are at an increased risk of falling victim to this exact scenario
My understanding was that gadolinium was already only used in cases where a normal MRI would be ineffective.
I don't know how the risk is actually communicated to patients. I imagine it varries by country. However, normal medical ethics would be to explain risks to the patients. Is there a reason to believe that isn't happening?
There’s really a risk vs benefit. If you have a brain tumour you need contrast to assess the type of tumour, its growth, if it’s a glioma whether it’s transformed and so on. If someone is being given contrast it is going to change their clinical management.
It seems an odd fixation of just MR contrast when the same could be said of all drugs. Does your doctor/surgeon go into the minutiae of all drugs and possible consequences? By this line of thinking, saline is not without risks, should they go into depth about that?
People already poorly retain information or even comprehend it at appointments or interventions, is there any point adding more burden onto their attendances?
Nobody explains shit like this. They will turn down the risks because if they were honest, most wouldn't accept that risk. Because the risk is PERMANENT life changing condition.
There is a risk of a permanent life changing condition when you take a bite of food, or have your blood drawn.
>>> Yes. The problem is that it's common in the industry. But it's ultimately up to the patient. Maybe alone. Pretty much guaranteed scared. Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress.
> There's a big difference between not getting the MRI and getting the MRI without gadolinium. My suggestion is to ensure that people know the risks outside of just the people who work in it. I'm not sure how that didn't get across in my original comment. With your comprehension skills, you are at an increased risk of falling victim to this exact scenario
I don't see anything wrong with the GP's comprehension skills.
Anyway, every procedure has risk - and no procedure is recommended if there is not an offsetting clinical benefit. There are clear guidelines for when gadolinium is to be used for an MRI and the guidelines factor in risk for 'NSF'.
There have been no cases of NSF in over ten years after newer gadolinium contrast agents have displaced the problematic ones.
I went hunting for a reference for your statement, and was successful.
Clevland Clinc says "There haven’t been any new reports of NSF in almost 15 years" [1]
[1] https://my.clevelandclinic.org/health/diseases/17783-nephrog...
When I had mine I got the form with warnings about side effects. When I saw the allergic reaction I was a bit concerned, I asked the tech and was told it wasn't a big deal. Since I was in the basement I didn't have service and I decided to trust them given the large number of my friends who've had MRIs. It was fine, but it seemed like a major thing to toss in the patients lap right before they get strapped down in a tube.
But there’s a potential risk of an allergic reaction to any drug you take, any food or drink you consume, even environmental substances - perfumes; hayfever is an allergic reaction to pollens. You don’t know you have one until you have the reaction. I didn’t know I was allergic to penicillins until I needed them for an infection and it turns out I am.
People getting MRIs frequently have bigger fish to fry.
When my wife was under cancer treatment she had them frequently. Risking some minor reaction, which in her case was disclosed many times, was well worth the value in managing the acute and long term treatment plan.
> Undereducated, worrying about their likely life threatening potential illness or injury. That's basically under duress
I was never communicated about gadolinium pollution. Not once.
And yes, on my recent MRI, I explicitly asked why there was metal particulate in my joint. "I dont know, sometimes it happens'... No you fucking tool of a doctor. Its gadolinium.
And I finally find out here.
Are you certain it is gadolinium? As I recall from a family member's health issues you can get particulates in joints from arthroscopic surgery or from the metal implants. Not saying that is what happened in your case, but I'm just curious because I remember reading about metal in joints as a potential side effect of the surgery.
That's somewhere between a Hobson's choice and Russian roulette.
I find it odd that when I happen across an article talking about some negative links between x and y being discovered, there's always someone in the comments saying this was known for some decades.
As someone with CKD and scheduled for an MRI, this was anxiety-inducing.
The Cleveland Clinic has a good overview[1]. Since there have been no reports of NSF in 15 years, I don't think it's rational to avoid MRIs based on gadolinium retention concerns.
[1] https://www.ormanager.com/briefs/study-mri-contrast-agent-ca...
[1] https://my.clevelandclinic.org/health/diseases/17783-nephrog...
That’s just the OP url again, I think you miscopied.
Yep.
https://my.clevelandclinic.org/health/diseases/17783-nephrog...
Note that MRI with contrast has very low risk and I am not aware of any evidence that Gadolinium retention even has adverse health effects. It is a concern though and this is why it is being studied. But I do not think the use of MRI contrast agents is something anybody without kidney disease should be concerned about. In general, risks and benefits must be balanced for any medical procedure. Such risks are continuously monitored and studied and guidelines are formulated based on this. Also consider that there is very clear harm from people being scared away by misinformation from medical procedures they would benefit from.
Sometimes I wonder if metals in the body can pick up cellphone signals.
Nobody told me gadolinium can be retained before I had it the first couple times.
Like somebody else mentioned, they swore up and down it's perfectly safe.
> Nobody told me gadolinium can be retained before I had it the first couple times.
The reason these publications exist is that this is new knowledge
> Like somebody else mentioned, they swore up and down it's perfectly safe.
I am positive that you were not told that '[gadolinium] is perfectly safe' because there is a well-known complication of gadolinium administration. It's rare, but it's mentioned in every consent form.
> I am positive that you were not told that '[gadolinium] is perfectly safe' because there is a well-known complication of gadolinium administration. It's rare, but it's mentioned in every consent form.
Consent is not "Sign this cause its the only course of treatment". And thats what happens almost every time.
And yes, I too have gadolinium retention in my joint. 3 MRIs. And no, was not told this was a complication... But I'm sure the papers I signed included weasel words to that effect.
> And yes, I too have gadolinium retention in my joint. 3 MRIs. And no, was not told this was a complication... But I'm sure the papers I signed included weasel words to that effect.
The presence of the gadolinium is not a complication. At best, it is an unintended side effect whose clinical significance is not known.
A complication is an unexpected/non-routine, negative outcome. We now have learned that the deposition is something to expect. There is no new information around clinical changes that one can attribute to gadolinium.
On my recent MRI, it caused significant metallic cloudiness in interpreting. It was metallic cloudy specks everywhere.
Making every future MRI worse is of large concern, especially if there are other nonmetallic contrasts.
> On my recent MRI, it caused significant metallic cloudiness in interpreting. It was metallic cloudy specks everywhere.
I am sure this is true - and it also occurs in people who get braces, certain piercings, people who have had implants or (unfortunately) gun shots.
These aren't complications in any sense of the word.
I think you must have misunderstood where the artifact was coming from. Gadolinium retention has been shown to occur, but has not been reliably linked to any clinical symptoms. Gadolinium tissue retention also does not interfere in interpretation.
Metallic cloudiness isn't a thing in MRI.
The more I see these types of things the more my skepticism shoots up when someone tells me something is perfectly safe.
There's a subreddit, created August 2024, discussing this: https://www.reddit.com/r/GadoliniumToxicity/
There are risks with every procedure and medication.
A dose of ibuprofen could give you Stevens–Johnson syndrome or TENS and you end up in a burn war for months.
Patients should be made aware of all the risks for any treatment, but it would be impossible to avoid they edge cases even with relatively basic medical care.
Most people lack the medical literacy to understand any of this. People don’t read their letters telling them to not eat before surgery, are they going to read the list of potential side effects of a medication? How many people read the information sheets that come with their prescription medication?
This isn’t newly known, but it’s convenient to stay with the comfortably familiar until the better alternative is forced.
Great. Only this year, I got roughly 6 doses of gadlinium, and prior to that, I got one every year, going back 20 years. I just recently chatted with a MRI nurse about the fact that I have a bad feeling about getting that stuff so frequently over time, and she dismissed my concerns. They used to remind patients to drink more after the MRI, but even that routine has been ended roughly 5 years ago. Is there anything else I can do except drink more on the day of the injection?
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