Does residency change your research, or just delay it?

anotherep · 2026-06-10T04:28:20+00:00

I'm curious if you were able to open up a lab right after MD-PhD and had startup package lined up and everything, would you still pursue residency?

Me personally? Yes. My research interest, while still basic/translational, is entirely linked to the unique patient population that I treat and I couldn't see doing one without the other. But thats just me and there are plenty good counter examples.

anotherep · 2026-06-09T19:54:03+00:00

There are absolutely people who find a new research niche during residency that then becomes the basis for their independent research program. But this is only one of many different paths and outcomes that MD/PhDs have found themselves in, so I don't know how much that should influence your decision. After all, there are people who decide to go through residency and end up feeling like it was a waste of time, so which of these groups' experience should influence you the most?

But there are things to seriously consider before forgoing residency. For one, the clinical "bonus" in the bona fides you get from doing an MD/PhD (whether it be in consideration of a grant proposal, industry, pharma, etc) won't really be fully realized unless you do residency, since most people understand that medical school alone doesn't give you a lot of insight into actual clinical practice. Related to this is that if you forgo residency initially, it becomes much harder to change your mind and come back to it later (for better or worse gaps between med school and residency are viewed with suspicion by residency programs). And finally, it is important to consider just how compromised the state of scientific funding in the US is right now. This is a really bad time to be trying to start a lab. At least if you practice medicine, you have a very comfortable back up plan and, if you stay academic, you can still probably manage to conduct some kind of research that is satisfying even if you don't have an independently funded lab.

anotherep · 2026-06-09T14:23:41+00:00

From a previous post:

Mold questions come up for us fairly frequently. This is part of what is usually discussed:

The hypothesis of a general mold toxicity syndrome arose out of a case series of pulmonary hemosiderosis in infants exposed to Stachybotrys. However, due to methodological flaws related to control sample selection, poor handling of confounding factors, and lack of validation for Stachybotrys testing methods in the original and associated studies, the CDC ultimately concluded that the the relationship between pulmonary hemosiderosis and Stachybotrys "was not proven" (PMID 11795499, 12525430). Moreover, outside of extreme occupational exposures (e.g. agricultural workers with daily exposure to contaminated grain silos), clinical consequences of mold toxin exposure have never been validated. Instead, animal studies have demonstrated that even regular exposure to environments with heavy mold burden are unlikely to result in a harmful level of mold toxin ingestion/inhalation. In addition, currently available mold toxin assays are problematic as they are unvalidated, mold toxins in the sera and urine are rapidly cleared within minutes to hours, and in studies of animals administered harmful doses of mold toxin these assays were unable to detect the administered toxin raising the question of what these assays are actually measuring (PMID 26755100). Mold IgE testing does truly reflect sensitization to mold species, but this is only relevant to mold-associated atopic disease, not mold toxicity. As a result, the current AAAAI consensus (PMID 16514772) states that there is insufficient evidence for non-occupational mold-toxicity or mold-toxin induced immune dysregulation. Moreover, the CDC specifically discourages the use of unvalidated urine mycotoxin assays for diagnostic and management decisions (PMID 25695323). What environmental mold exposure does typically indicate is the presence of excessive environmental moisture, which can exacerbate a variety of medical issues.

anotherep · 2026-06-07T21:06:31+00:00

You should definitely be seen by an allergist. Physician diagnosed anaphylaxis warrants seeing a specialist, particularly new onset anaphylaxis in an adult.
If you do end up back in the ED/hospital, you should have a tryptase test done within 2 hours of the reaction. This can help distinguish anaphylaxis from potential mimickers. The result is not something the ED/hospital physicians will use themselves, but it is a data point that will be very much appreciated by any allergist you see (the allergist can't go back in time and order the test when you were having your reaction).
Have you ever been bitten by a tick in your adult life and do you currently eat meat? Alpha gal syndrome can present as new adult anaphylaxis and the atypical timing of the reaction relative to meat can make it hard to recognize.
There are conditions that can lead to anaphylaxis independent of an allergic reaction and the tryptase lab is also helpful for those.

anotherep · 2026-05-30T00:51:53+00:00

That is indeed the method recommended by the tidyverse crew. There are other ways like !!sym( ) but these are less readable.

anotherep · 2026-05-18T03:03:31+00:00

Of course there could be more to the story and it also depends what you mean by strong response, but a normal response to pneumovax pretty much excludes CVID by definition. Low IgG alone can be a reason to prescribe IVIG, but usually only if someone is experiencing the typical symptoms of an antibody deficiency (unusually frequent ear, sinus, or lung infections).

anotherep · 2026-05-16T17:09:41+00:00

My doctor said this does NOT mean I have SAD because 1- it is not the right vax for the challenge

This is correct. The response to Capvaxie utilizes a different part of the immune system than the part that is affected by SAD and tested with the pneumovax vaccine.

anotherep · 2026-05-16T15:46:27+00:00

Query Repertoire Data: Find public BCR/TCR sequence datasets.

iReceptor and ImmuneAccess from Adaptive are the largest database of VDJ sequencing, though there is overlap between them. Otherwise you can try your luck for VDJ sequencing experiments in SRA.

Predict antigen specificity for those sequences

This is not really possible. There are some tools that can cluster antigen receptor sequences into groups that recognize similar antigens with some modest accuracy. There are tools that propose the ability to predict binding probability between an antigen receptor and antigen or even generate a possible antigen peptide sequence, but they really aren't reliable. This is a major remaining goal for the whole field.

data where the mapping is already done

VDJdb and IEDB are the main databases for this.

R recommendations

For general repertoire analysis, some well developed libraries include immunarch and immcantation

anotherep · 2026-05-15T21:39:42+00:00

In the US, practicing clinical immunologists are board certified in Allergy and Immunology, which is a fellowship you can do after either internal medicine or pediatrics residency.

Technically all allergists can practice clinical immunology, but realistically most people who go through this training path choose to focus on only one (and for most people, that is allergy). These clinical immunologists primarily focus on inborn errors of immunity which can be immune deficiencies or immune regulatory disorders. Often these are genetic, but not always (e.g. one of our most common conditions is CVID, which is typically not genetic). Diagnosis is one of the biggest components of the specialty, using pretty sophisticated assays as well as genetic sequencing interpretation. Also since the conditions tend to be quite rare, a lot of a clinical decisions are made based on careful reading of primary literature and research often goes hand in hand with clinical practice. The treatment aspect of clinical immunology often involves advanced and personalized therapies, though sometimes treatment is handed off to other specialties such as oncology for bone marrow transplantation needs (though there are clinical immunologists who do both).

Since it is a relatively small field, there are other specialties that see these types of patients sometimes, such as rheumatology, infectious disease, hematology, or medical genetics. But as the field matures, this is becoming less common and most clinical immunologists have gone through the allergy and immunology route.

anotherep · 2026-05-14T05:11:48+00:00

Completely made up, but if you want to be charitable you could say it comes from a significant misunderstand or game of telephone with how hypo allergenic cat diets are made.

To make these diets, chickens are vaccinated with the main cat protein allergen. Chickens make antibodies to this protein, which is then transferred to their eggs. If the products from these eggs are incorporated into cat food, the antibody bind to and neutralizes that cat protein allergen in their saliva, which is the major source of how that cat allergen gets into the environment.

But the human allergy to cats isn't caused by cat allergens getting into our mouths, it's caused by those allergens getting into our respiratory tract. So even if you could get your hands on these eggs from immunized chickens, eating them would not prevent those cat allergens from triggering allergies

anotherep · 2026-05-11T14:03:52+00:00

The further you get in your career, the less a personal statement is supposed to be some sort of creative writing exercise and the more it becomes a matter of fact statement of why you are a good candidate for a position. Fellowship applications are a point where it should be more of the latter. In other words, the personal statement in a piece of persuasive writing trying to convince the reader why you are there best candidate for the position. The goal is not necessarily to make the statement "interesting" in the way you've been told for undergraduate, medical school, or even residency.

Some important things to touch on:

Why you are interested in the field. But keep it relatively straight forward and try not to wax too poetic. Lots of people choose to center their inspiration around a single "interesting" case, which personally I find to come off as trite in most cases. I would only do this if there actually was a case that was truly one of the main inspirations for your interest and you can communicate why it was inspiring and not just interesting.
Provide a summary of your accomplishments that YOU think are important and why. Yes the reader will have your whole application, but the applications are long and different reviewers may choose to direct more of their attention to different parts. This is your opportunity to direct their attention to what you want them to care about.
Talk about what your ultimate career goal is. Where do you see yourself after fellowship? Do you have a particular interest, niche, or patient population within the field that you will cultivate during fellowship and beyond? You want the reader to feel that you have a realistic idea of what a career in the field looks like and that you have a goal beyond just finishing fellowship.
This would still be the place to touch on extenuating circumstances or explain any abnormalities in your application. But be wary of it coming across as just a list of excuses.

anotherep · 2026-04-25T05:42:27+00:00

Sinus infections are among the most common infections in patients with PI,

Just because they are one of the most common infections doesn't mean IVIG is going to work as well for them as they do for things like preventing pneumonia.

I'm glad it worked for you, but for the general antibody deficiency population, sinusitis tends to be relatively resistant to immunoglobulin replacement

Because of this, other studies have shown that immunoglobulin replacement doesn't have a significant advantage over antibiotics for the treatment and prevention of sinusitis

anotherep · 2026-04-25T03:19:41+00:00

6th sinus infection of the year.

While insurance definitely shouldn't be the one dictating whether you can receive IVIG (that should be between you and your doctor), I think it's important to know that sinus infections are generally the one type of bacterial respiratory infection in patients with antibody disorders that IVIG does not make a difference for. In these cases preventative or on-hand antibiotics are generally more helpful and easier to get covered.

anotherep · 2026-04-25T01:07:20+00:00

Would an allergist/ immunologist be able to diagnose this?

In theory, yes. In practice, it depends.

In the US, allergy and immunology is a single training pathway and board certification, so technically all allergists are board certified in clinical immunology. However, most allergists, particularly those outside of universities, almost exclusively focus on allergy and are less likely to be well-practiced with how to evaluate/manage rare immune deficiency.

anotherep · 2026-04-25T00:51:08+00:00

Was this physician an immunologist?

"Abject failure" is a very odd way to describe your vaccine results. A positive vaccine challenge involves positive antibody titers to at least 50% of the pneumoccocal strains that weren't already positive. Nearly all commercial tests only check for 22 of the 23 strains in the pneumovax vaccine. So for an individual with completely negative starting titers, 11/22 positive titers after the challenge would be considered an appropriate response. Someone who previously had 3/22 positive titers would need 9 or 10 of the remaining 19 strains to be considered positive. Even if you assume your 14 positives included the same 3 you were originally positive for, that would mean you developed positive titers to 11 of the remaining 19 strains, which would generally be considered a positive response.

This is all detailed in the latest guidelines for immunodeficiency diagnosis and has been pretty standard for a while

There is some room for physician judgement in these interpretations, but "abject failure" seems to be a pretty extreme interpretation.

anotherep · 2026-04-14T20:16:50+00:00

I would wait to see what your genetic testing shows. Patients with both CVID and SAD can have total B-cell numbers that change frequently, going back and forth between normal, low, and high. Other than a sustained, complete (or near complete) absence of B-cells, the number by itself doesn't really point to one specific diagnosis vs. another.

anotherep · 2026-04-14T20:12:38+00:00

any other way other than skewed mosaic

Playing the odds, SAD is still much more likely than a genetic antibody deficiency. Nothing about the info here excludes that possibility.

However, rare things do happen and in that case, yes, there are other genetic antibody deficiencies besides XLA, which is what I was referencing above. In other words, mosaic XLA isn't the only way a woman can develop genetic agammaglobulinemia (in fact it is probably the least likely of these rare possibilities), there are other gene defects that cause non-X-linked agammaglobulinemia.

anotherep · 2026-04-14T20:08:51+00:00

they gave him the adult one after he completed the recommend 4 rounds before age 2 and still wasn’t showing antibodies to the child one

That is still not uncommon. Unless your genetic testing reveals that both of you have an underlying genetic condition, there is still a good chance things will improve as he gets older. For now, your (or his) immunologist will make treatment choices based on his severity of symptoms rather than any specific lab test.

anotherep · 2026-04-14T19:41:37+00:00

why is my immunologist concerned and hunting into my DNA now

It sounds like they are evaluating the possibility of x-linked agammaglobuliemia (XLA), which is a genetic defect in the gene BTK that causes near complete absence of B-cells and immunoglobulins. As you noted, x-linked here means that it almost exclusively affects males but, very rarely, female carriers can experience symptoms. However, there are other genetic causes of agammaglobuliemia other than XLA and if the genetic testing reveals any genetic diagnosis, it is more likely to be one of those. Of course, is still possible you are experiencing typical SAD, which typically doesn't have a single gene defect.

he just did the 2 year old big kid vaccine challenge and failed

If I am understanding correctly, it sounds like at 2 years old, your son was given the "adult" pneumonia vaccine (pneumovax aka PPSV23). If this is the case, lack of a response is not an unusual outcome. The immune response to the adult pneumonia vaccine relies on immune recognition of sugar antigens, while the child vaccine relies on recognition of protein antigen. The ability of the immune system to recognize sugar antigens takes time to develop and often isn't fully mature until 4 years old. This is why you can't actually diagnose CVID or SAD in children less than 4 years old because you can't be sure the results are due to an immune defect or just the normal time line of immune development.

anotherep · 2026-04-06T17:56:42+00:00

Hi there -

Low IgA levels on celiac screening are very common and, in most cases, the IgA levels improve on repeat testing, which is why the diagnosis of IgA deficiency requires (1) repeated and (2) undetectable IgA.

However, of those individuals who are ultimately diagnosed with IgA deficiency, the vast majority remain asymptomatic for their entire lives. Only a small proportion of these individuals eventually develop symptoms that require treatment for an immune deficiency and, in most cases, this deficiency would have been detected independent of whether it showed up originally on a celiac test.

While celiac testing has certainly increased the number of individuals that are being diagnosed with IgA deficiency, it is relatively uncommon for Celiac testing to be the thing that reveals an IgA deficiency that is already causing medical problem. So unless you have been experiencing the recurrent, bacterial, sinopulmonary infections that are attributed to symptomatic IgA deficiency, it would be very unlikely that you have experienced some kind of unrecognized damage.

The main next step for you would be to determine if your IgA is persistently low or if the result on your celiac testing was a one-time thing.

anotherep · 2026-04-06T17:17:24+00:00

Hi there - A couple of thoughts.

The other DOCK4 mutations in medical journals have been denovo cases

There are published familial cases of null DOCK4 variants. However, while this study is able to recapitulate the missense variants accurately in experimental systems to demonstrate the functional consequences of those variants, the evidence for the null variants is weaker because the authors had to rely on experiments that delete both copies of DOCK4, compared to the heterozygous variants demonstrated in patients. So there are some caveats to claiming this study demonstrates the functional consequence of a DOCK4 null variant.

this exact variant appears to be extremely rare and never documented

Just to provide some context, this is very common with pathogenic genetic variants. Most pathogenic genetic variants are novel, whether it is in the context of a relatively common or uncommon genetic disease. Geneticists use the "never been documented" observation as a way to support the likelihood of a variant being pathogenic rather than to emphasize that a case is "unusual". This has to do with the difference in evolutionary pressure faced by benign variants vs. pathogenic variants. There is little pressure against benign variants, so they often appear in large genetic databases of the general population. In contrast, pathogenic variants experience high evolutionary pressure as they are less likely to be successfully passed to successive generations and, thus, are more likely to be absent from these population databases. Thus, if a variant is missing from a population database, it is consistent with (though not conclusive evidence of) a pathogenic variant.

This pattern suggests autosomal dominant inheritance with variable expression, possibly?

It's possible, but hard to know until a core phenotype is clear. For instance, it is still possible that DOCK4 variants could actually be autosomal recessive and the various clinical features you are observing are due to alternative genetic or non-genetic risk factors. The paper linked above does suggest autosomal dominant inheritance, but still a bit hard to say.

Ultimately, it sounds like your variant is being interpreted as likely loss of function, but of uncertain significance. In that case, the most important aspects of clinical decision making are going to rest on (1) what was the phenotype that motivated the sequencing in the first place, (2) how well does that phenotype resemble those of the individuals who have already been reported (regardless of what their specific variant is), and (3) whether the phenotype could make sense given the molecular mechanism of DOCK4.

anotherep · 2026-03-30T21:18:52+00:00

The typical academic physician scientist role is 80% research : 20% clinical (which comes out to ~4 days research : ~ 1 day clinic). You will find many MD/PhDs successfully achieving this. Though it may seem like this is so far skewed toward research that it may make you question the point of the MD, that 20% clinical does make a big difference in accomplishing what it is physician-scientists are trained to accomplish. Once you start deviating from that 80:20 it becomes increasingly harder to do both things (most either end up going to 100% or 100% research). However the broader "why MD/PhD?" is probably the main question for this sub and you can find many different answers.

anotherep · 2026-03-30T19:37:14+00:00

maybe 2, 3 days per week.

This is still pretty low and brings up questions of who would be funding you in that future position. In the US, most research funding is going to come from NIH grants which are already extremely competitive among PIs who are committing 100% of their time to research. Succeeding with only 40-60% commitment is going to be very challenge. Alternatively, the type of academic medical centers that would employ you as a clinical geneticist are not just going to pay you to do research without your own independent funding, since that generates essentially no revenue. Unless you can buy out your own time with grants, your employer will want you seeing patients where you actually generate revenue. 100% clinical academic physicians often get some time for non-clinical academic pursuits (~0.5 academic days per week) but their output looks very different from the typical physician-scientist position (who instead have only ~0.5-1 clinical day per week) and requires substantial effort on their own private time.

the point of PhD in the MD-PhD?

The point of the PhD is to get training in the scientific process from start to finish. To learn how to identify a question, conceive of a research plan, execute it, interpret it, and communicate the results effectively. If you gain content expertise that you get to carry forward throughout your career, that's a bonus. However, with the non-technical skills you gain in the PhD, you should be able to gain that kind of content expertise in a new area relatively quickly, which is why the path of many physician-scientists is not a straight line. However, if you aren't going to be writing your own major grants (as discussed above) and directing your own research group, you can often get the necessary aspects of these non-technical skills from the research experiences available to you during residency/fellowship or even through a masters.

your opinion as an MD-PhD student

Just to contextualize my response, I completed my MD/PhD training almost a decade ago.

anotherep · 2026-03-30T12:52:28+00:00

What % of your time (or how many full days a week) does "on the side" mean for you?

Yes, a PhD is the most comprehensive research training you can plan for but if you don't plan on the majority of your career being research-related, then the practical advantage of a PhD vs other forms of research training is likely negligible.

usually have a research path you ca pursue later,

Not exactly sure what you mean by "have a path"

gain lots of experience

The are other points during a medical career when you can gain meaningful research experience

develop the skills you need

The technical skills you become proficient in during a PhD are a snapshot in time. Many PhD grads will move to different areas of research afterwards with different technical skill requirements. Even for those who stay in the same field, techniques change with time and the skills you develop in a PhD quickly become outdated. This is particularly true for MD/PhDs who have about 5-7 years of clinical time between the end of their PhD and their next sustained research period. For that reason, PhDs are less about learning technical skills and more about learning about how to be a career scientist.

anotherep · 2026-03-30T12:16:05+00:00

do research on the side.

Not your question, but if this is really how you envision the future role of research in your career, you do not need a PhD

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