Week 7: Safaa Mouline

This week, I presented at the Tuesday meeting. While this presentation was focused on some of the analysis I've been doing using the entire MS dataset (890 patients), I've recently started looking more into grouping patients by age and sex and running analyses on subsets. I don't currently have menopause data in the dataset I have, but if an MS-menopause grant goes through, this data will be collected and I should get access to it (it's kind of crazy that there are only about 10 papers on MS and menopause total, given that MS affects women 2-3x more often than men and a lot of women are going through menopause right around the age when disease progression tends to accelerate). In the meantime, I was hoping to use age as a proxy for menopause status with the dataset I currently have. I know it's a longshot, and as you'll see below, the proxy doesn't really hold up. But here's what I tried and what worked and what didn't.

I grouped patients into four groups: female 40-55, female 55-65, male 40-55, and male 55-65 (which I believe matches the age ranges in the grant). EDSS increased significantly with age in both women (p=0.0004) and men (p=0.0088), but there was no significant difference between sexes within the same age band. The sex-age interaction in the OLS model was trending but non-significant (p=0.082). SC and FC comparisons between age/sex groups showed nothing surviving FDR correction, and subgroup ridge regression models ended up too noisy given how small the groups got after stratification.

Regarding the mediation analysis, age -> sex -> EDSS, I tried this in both the 55-65 age band and the full dataset. While the total effect of age on EDSS was highly significant (p=4e-20), the indirect path through sex was not significant in either case (p=0.59 in the full dataset, p=0.28 in the 55-65 band). As Sandra mentioned, all pathways need to be significant for mediation to work (age was not significantly associated with sex (p=0.49), which makes sense, and sex was not significantly associated with EDSS after controlling for disease duration (p=0.28)). I also tried using lesion volume and thalamic volume as the predictor instead of age, with sex as the mediator, but the sex -> EDSS path remained non-significant in both cases, so the prerequisites for mediation were not met regardless of the predictor used. 

I’ve also been trying to see if there are any connectivity differences. After trying a few different things with this, I got something that could be interesting. For structural connectivity, 82 SC regions significantly correlate with age in female patients (FDR corrected) versus only 24 in males. For functional connectivity, 2414 FC connections correlate with age in female patients versus 466 in male patients, roughly a 5-fold difference. Maybe this can be the start in showing that aging has a much more widespread impact on brain connectivity in female than male patients with MS (which might be related to menopause?). I'm still looking into this, and obviously it's impossible to draw any real conclusions without menopause data. 

Okay, those were my project updates, but the highlight of my week was being in the OR for the first time. I joined Justin, Pooja, and Alex in shadowing Dr. Spector in plastic surgery. I witnessed a breast reduction, a skin graft for a burn victim, and adding DermiSphere hydrogel to a patient with head and neck cancer. This was my first time seeing invasive surgery, and I have to say: surgery is insane. Imagining it, or even watching it in shows, is not at all comparable to seeing the incisions and smelling the cauterizing live right in front of you (I did indeed have to step out a couple of times). I knew this going in, but seeing how open and bloody everything actually was made it ring even more true for me, that in some way, it's a counter-intuitive process to cut things up in order to make them better (maybe that's just me, since I can't imagine myself holding the scalpel). During the breast reduction, at one point I was confused about how the surgery would wrap up because so much looked open, but it somehow all worked out. The cancer case was especially devastating, and what Dr. Spector was doing was seeing if the DermiSphere took and adding a second layer. It was impressive witnessing how all the doctors in the room worked as a unit, without necessarily communicating much as they were working. It is also heartbreaking to see some of these cases, and it's a reminder that there's a difficult story behind most of these procedures, not just the technical side of it. 

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