No, it's OK. OK, so thank you to my mentor who couldn't be here today, Dr. Chong Kim. So the title of my presentation is Needle Depth of Fluoroscopically Guided Intraarticular Corticosteroid Injection. So intraarticular corticosteroid injections to the knee are a very common procedure throughout physiatry and beyond. Many practitioners perform these injections in an office-based setting with landmark guidance, as well as with ultrasound guidance and in the fluoroscopy suite. When performing a landmark guided injection, it can be challenging to confirm that you're in the intraarticular joint space and the medication is reaching the appropriate place. This presents a challenge since many practitioners do not have the time or availability of ultrasound or fluoroscopy. So our team sought to determine the needle depth required to enter the intraarticular space of the knee joint. So this was a prospective cohort study in an academic medical center. We enrolled 34 individuals who underwent intraarticular corticosteroid injection of the knee under fluoroscopic guidance. All underwent injection with the knee bent at a 90 degree angle with an inframedial approach. All injections started with a 1 and 1 1 inch needle with the needle hubbed. Contrast was then used to determine the depth that the needle required to reach the intraarticular space. In many cases, a larger needle was required and the 1 and 1 1 inch needle was needed to be replaced. So at the top box up there, we report the demographics of our cohort. As you can see, the demographics are a little bit skewed. We did enroll 27 women and only seven men. One major variable that we looked at was BMI. The average BMI for males was 46, whereas the average BMI for females was 39. So the graph below shows BMI versus needle depth required to reach an intraarticular space. And as you can see, there's a positive correlation with increasing BMI and needle length requirement. In total of the 34 subjects, in total of the 34 subjects, we needed the 1 and 1 1 needle was appropriate for 14 patients, whereas a longer needle was required for 20 of the patients. Of those with the appropriate intraarticular spread with the 1 and 1 1 inch needle, the average BMI was 34. And in those requiring the longer needle, the average BMI was 45. So in total, the average needle that was required across all subjects was 1.99 inches. We show a positive correlation between increasing BMI and an increasing needle depth requirement. So in conclusion, we show that it might be beneficial to use a longer needle in those with higher BMI for this common procedure. And that's it. Question. Thank you. Hi. So you determined the switch of the needle based on contrast in the joint? Mm-hmm. And it was two views or one? Sorry? You took two, like you took an AP and a lateral or you just didn't? I believe they did both. Yes, I believe we did both. Sorry I wasn't present for all of them. Oh, and then were the patients selected based on BMI initially? Because the average BMI is pretty high. No, so we tried to have a range of BMIs. So it was just individuals who needed the injection that we would have enrolled. So I think I might have misunderstood. What was the average BMI of the patients that you did this procedure on? Average BMI in total was 40.61. Yeah, it's sort of reminiscent of what we what we see. How generalizable do you think that, I mean that's pretty high BMI? Where I work I think that's pretty average. So you approached it anteriorly? Sorry? Yeah, in for a medial. So the injection, like most of us who are orthopedically trained, don't go through the fat pad. So that's basically an anterior approach. I know it's inframedial. I know what it's called. But it's an anterior approach. You go in through the fat pad. Bad things happen when you stick a needle through the fat pad, especially the cortisone will leak out. And what happens to the fat cells? Necrosis. Now it hurts when you kneel and squat and do other things because you don't have your fat pad. So it's really important to have a fat pad. So what happens if you change your approach? You've got fluoroscopic guidance, right? Change your approach. Redo this. Change your approach. See what happens. See what your numbers are. to see that needle go into the joint. So could you argue that if you had an ideal guidance, it would be direct visualization or ultrasound, right? Yeah, and many practitioners do. I would say as a resident currently, I've seen everything and anything used. So I do think that there are still quite a few people that are using landmark guidance, but when ultrasound is available and the timing is feasible, I do think it's a great option. And I think that it's better for a visualization of the injection. Agreed. How many of you were residents? What about fluoroscopically-guided procedures? Are you guys getting exposure to it? by contrast Yes Yeah, so the reason I asked because when I've done thousands of blind ones Without a thousand with ultrasound the only indication I have with the contrast enhances people who pay for PRP injection to the knees and if I know that it The defect is on one side of the joint versus the other one I tried to get the contrast on that side, so I tried to be specific But that's the only reason I would do it with x-ray guidance and because of the fat pad and many other Considerations, so I was just wondering what was their definition of proper? intraocular placement and contrast I'm not I'm sorry. I'd have to ask my my mentor exactly what he meant by that. I'm not sure the question So to speak and then you base it upon that Whenever you talk about the you know, the the proper technique, so it's always important to know what you're you know What you're dealing with and how you're deviating from that and oftentimes we do deviate because that's how many things Get advanced. Mm-hmm What do you think the generalizability of this the idea to other joint injections I mean, I I think it'd be interesting to look at other joint injections to like I said, there's a lot of different Approaches that we do to other joints that are in office and landmark base So I think it'd be interesting to look at that as well any thoughts from the audience about Where they would go with this how to explore So, yeah I'm just thinking what other injections are we doing blindly because the goal of study was to see if People that are doing these blind injections are even getting in the joint. So like a subacromial I mean a lot of people are doing subacromials blind. I think that would be like the next But sounds like the initial study was what is a one-and-a-half inch needle sufficient or not because either it was a you use a one-and-a-half inch or you didn't and No, just one quick question, because I don't do these. Is there a fault with using the long needle all the time? Like, is that more painful, dangerous? You know, it really depends on technique. You know, I think longer needles, they more easily bend. You need to have a finesse. You know, I wouldn't suggest it if you're new to needle management. Mark, do you have any thoughts on that? with that one-and-a-half inch, you know, I stop at about a third of it, probably, because you're going to feel it, and a lot of times you'll come in to either the medial aspect of the lateral femoral condyle or the lateral aspect of the medial femoral condyle, and you feel it bump against that, and you pull back a little bit, squirt it, right? The cruciates are going to be fine, and, but, yeah, usually it's a one-and-a-half. I mean, every now and then somebody's really petite, and I'll use a one-inch. Yeah, but the standard one-and-a-half for most people, but, yeah, I mean, it's a, you know, the study's a great idea, right? It's not a bad idea, and it's not a bad idea to do it in every joint, to see what, if it is, because it's, you know, we're all hypothesizing they're so big, I don't know if I got the damn needle in, right? Sorry. You don't want to say that, do you? Sorry, but, yeah, I mean, subacromia, you think it's, like, gigantic, right, the space, but. The thing is most of the patients are afraid of the length of the needle. It doesn't make a difference. It's actually the thick. It's not the needle, it's the gauge. Exactly, it's the gauge, you know, so the gauge is the. You see it afterwards, and they go, oh. Yeah. OK, Rebecca, thank you very much. Thank you. Is David here? No David. OK. Now we welcome Campbell Miller. So the title is the Effective Training Presence in Fluoroscopy Duration on Intra-Procedural Pain Scores in Fluoroscopic Guided Musculoskeletal Procedures, a Sub-Analysis of a Retrospective Observational Cohort Study. It's a very long title. I'd like to thank, and my name's Campbell Miller. I'm a fourth year PM&R resident at the University of Utah. I'd like to thank my research mentors, Dr. Daniel Cushman, Aaron Conger. Awesome, thank you. All right. Well, I won't reread the title. But the purpose of this study was to try and help determine if trainee presence or performance in musculoskeletal fluoroscopy-guided procedures affected the pain experience of patients during these procedures. As a resident, I've experienced firsthand the understandable concern that some patients may have when a trainee is either in the room or particularly when they're actually about to be involved in a procedure. And so I was hoping through this sub-analysis to provide some evidence of reassurance for patients who are about to undergo these types of procedures. Also, just in general, there's a relatively limited amount of literature looking at trainee presence and interprocedural pain, especially in fluoroscopically-guided procedures. So regarding the methods in study design, so this was a sub-analysis of a two-center observational cohort study. I will say that the majority of the procedures occurred at the University of Utah. Patients underwent a range of fluoroscopically-guided MSK procedures at outpatient procedure clinics. On the bottom pie chart, you can kind of see the distribution of these different procedure types. I'll say the majority of the procedures were targeting axial, back pain, or radicular pain. The most common procedure type was a medial or lateral branch block at 449 procedures. There was a small subset, I will note, though, of peripheral nerve stem and genicular block, or RFA. Trainees were from the University of Utah ACGME-accredited puberty residency and sports med fellowship, as well as a NASS-accredited interventional spine fellowship. On the top pie chart, you can see of the 1,102 procedures that were analyzed, 340 of them had a trainee present, and 119 of them had a trainee involved in some way. The primary outcome for this sub-analysis was an intraprocedural pain score on a numeric rating scale from 0 to 10 that the patient reported immediately following the procedure. And then a secondary time point, or sorry, a secondary outcome was the fluoroscopy time for each of these procedures. So if you look at the histograms in the middle of the poster here, the blue histogram represents the percentage of patients who reported each individual pain score on that scale from 0 to 10. You can see it's relatively well distributed, but the highest percentage of patients did report a 5 out of 10 for their intraprocedural pain. And then the bottom histogram, the purple histogram, takes a look at the fluoroscopy time distributed throughout the procedures that were analyzed. And you can see from this histogram that the majority of procedures required less than 50 milliseconds of fluoroscopy duration. So to better answer the question of whether or not trainee presence or involvement significantly affected intraprocedural pain, we divided our data into three groups, trainee absent, trainee present, and trainee performed. And in these groups, we calculated the mean intraprocedural pain score. This is represented by the graph with the blue bars. So you can see in the trainee absent group, the mean pain score is 4.77, in the present group, 4.9, in the performed group, 4.76. Just visually, you can see there isn't much of a difference between the mean pain scores between these groups. But we did run a linear regression analysis, which did confirm this and demonstrate that neither trainee presence nor involvement significantly affected the intraprocedural pain scores. And then we did something similar with the fluoroscopy time. We took the average fluoroscopy time for each of these groups. And this is represented by the graph with the green bars. You can see in the trainee absent group, the mean fluorotype was 44.1, in the present group, 43.2. And then you can see there's a relatively significant jump to 58 milliseconds when a trainee was involved in the procedure in some way, which I think is not too surprising as it can take a little while to learn these procedures. We ran another linear regression analysis that did confirm that that jump was statistically significant. So what can we gather from this sub-analysis of our larger data set? I think first and foremost, if a trainee's gonna be involved in a fluoroscopy guide procedure, you can expect that it may take a little bit longer, as shown in our data set here. But based off this data set, there doesn't seem to be any significant effect on intraprocedural pain if a trainee is either present in the room or, again, involved in the procedure in some way. And so I hope this provides at least a little bit of evidence to help reassure patients who are about to undergo one of these procedures. That's it. All right, questions? Yes. Go ahead. So I do botulinum toxin injections, and the only times I've had patients tell me, you know, it didn't really work that well this time, doc, is when I let the trainee do it. But in those cases, the patient is looking at what's going on, they can see. In these cases, the patient can't really see what's going on behind them. So does the patient know, and the trainee performed, that the trainee is doing it, or is it just kind of happening? Yeah, that's a very good point. I would say, just anecdotally, from my experience, the patient typically does know. Usually the attending will mention that, you know, they may be involved in the procedure in some way. When it comes to the fluoroscopically-guided procedures, I haven't gotten to the point where I would be performing the procedure on my own. So it's more of a case of the attending does a number of the different injections, and then I come in and do either some needle driving or something like that. But I will say that I think typically they at least know that, they definitely know they're present, and they know if they're going to be involved, that they may be involved, if that answers your question. But it's a good point. Sometimes, yeah, when they can't see, it's tough to, yeah. It makes it even better that the pain score doesn't change. Yeah, yeah. I do think that's a very important element. I think as part of the informed consent, the patient should be aware that somebody else may or may not be doing the procedure. And I personally feel there should be a discussion with the patient before the procedure to allay any anxiety about what's going on. I certainly, if I was having a procedure done and there's a bunch of people in the room, I didn't really know who was what and who did what, I would be anxious. Yeah, sometimes there's a medical student resident, and there's a lot of people in the room, so yeah. Yeah, and from a medical legal perspective, so I'm on the Board of Medicine in my state, and I'm also on the Federal Commission, and I think it's really important that the patient understand and accept that somebody else may be training. I think most training institutions communicate that there are trainees involved, but I think each and every case should be treated separately. Do you know if you used sedation for any of these? We did. That was one of the variables. We did not use that in any of our linear regression analysis. I do have the numbers somewhere on my phone here, but yeah, we did use sedation in some of these, but we didn't look at that. We didn't compare the variables to trainee present training. So that's a huge confounding factor. You know, depending on the level, is it anxiolysis, is it sedation, you know, conscious sedation? Yep. That's something to really consider for a follow-up study. So, how long after are the scores done after they wake up? I think it was about... So when sedation wasn't used, at least, basically as they're about to get wheeled out of the room, they'd be asked what their pain was during the procedure, and then also would be asked what the pain was after the procedure. I think with sedation, typical... Oh, Dr. Kendall, did you have something to add to that? Yeah, so... Yeah, I think one of the greatest parts about it, it's just a large data set like Dr. Kendall said. So, there's a lot of different regression analysis and things that can be done to look at different variables. So, I think there's some good avenues to go with the data set. So. Yeah, I was just going to ask if there was any, so like there's a lot of different fluoroscopy procedures. Was there any subgroup breakdown based on the procedure that was being done? Like were you able to look like SI joint versus transferaminal, et cetera? I think that's a great question and an area for, an avenue for this to go to. No, but we didn't do any like subgroup analysis based on procedure specifically, but I think it's a great point because some procedures are probably more inherently likely to be more painful than others. So, I think that'd be interesting. Great presentation. Thank you. There is existing data for pain fellowships that show that the fluorotime in the beginning of a fellowship on a particular procedure, like cervical epidural steroid injections, this was published by Steve Cohen's group, is much higher than in, let's say, May or June of the fellowship. So, the time of the year very much matters. You said that there are NAS fellows associated here. The breakdown of which trainee was in the room is really important to this data because if you have a PGY3 PM&R resident who is uninterested in going into this subspecialty, they're going to take a little longer than a NAS fellow or a pain fellow who has devoted their career to this and read all the guidelines and things like that. So, that's, that's really important to the pain component and the fluoro component, and the time of the year really matters too. Thank you. That's a great point. I also think it'd be interesting if, I think the limitation would be documentation continue to be efficient in the clinic, but delineating when a trainee is involved in just a part of the procedure versus does the entire procedure too might make a big difference as well. But anyway, there's some different ways to go about continuing with this data set, so. I think it may be interesting at some point to look at if there are any differences in someone who's NAS trained versus. Does that generally happen, is there a sort of ramp up process? Is anybody using simulators or has access to simulators during their Thank you. Okay. I'm going to go to the University of South Carolina next year. Congratulations. Congrats. All right, we welcome William Naber who's very appropriately clothed like a Michigan resident and he's going to talk about the association between corticosteroid dose and pain reduction following sacroiliac joint injections. Hi, everyone. I'm Buddy. I am a PGY2 resident with not Ohio State. This is my contact information. Free hardball. And also, if you would like my contact information in the future for anything, I also include it in this QR code right here under References. So feel free to scan that. Before I begin, though, and talk about things, I would like to thank my mentors, Dr. Claire Kulpakshin and the illustrious Dr. Rishi Bakshi for the support with this project. I'm here to talk to you today about the association between corticosteroid dose and pain reduction following sacroiliac joint injections. So overview. So chronic low back pain is something that we as physiatrists see either in our training and our practice at some point. And the SI joint is a pretty common culprit for chronic low back pain. Additionally, corticosteroid injections have been used for over 50 years as a modality to treat things like interarticular pain. Despite this long-term use and the fact that major societies endorse it as an effective way to treat certain interarticular pathologies, there still remains sparse data guiding dose selection for patients. So at that point, as a learner, I ask myself, how are we deciding to do this? Are we using clinical gestalt citing our training or what's in the vial or whatever our reasoning is? And if so, are we using more of a Mandalorian-esque, this is the way mentality? Are we using evidence-based guidelines for actual practice? And I'm not disbarring the fact that our training is plenty of evidence, but do we have actual literature to back what we're doing in our training? So ultimately, I ask myself, why? Why are we selecting Ed Sears truly? Why are we selecting the doses that we do? And why are we, for some practitioners, standardizing the dose across, say, SI joints with 40-methylprenisolone when we have a patient population as variable as Muhammad Ali in his prime and Betty White in her golden years? So they're clearly two different people should they be getting the same dose and the same injection. So to answer this question, we performed a retrospective observational cohort analysis analyzing EHR data over a 6 and 1⁄2 year period. This captured 661 patients who received unilateral fluoroscopic injections by fellowship-trained interventionists. They received either 40 or 80 milligrams of methylprenisolone. And overall, we used a hierarchical linear regression model to analyze the variables, as you see in this table, with over 40 amputations. So the verdict. As we hypothesized, steroid dose played no clinical or statistical significance in change in pain scores. Additionally, age and BMI also didn't have any significance in change in pain. It was interesting to find that sex assigned at birth, so females, had less change in pain resolutions compared to males. So it approached significance. Additionally, our average follow-up was around 31 days. So pre-procedure scores were recorded prior to the procedure. Post-procedure scores were recorded at follow-up. And at an average of 31 days, it shows we had sufficient time for the steroids to take effect. So what's the big deal? First off, dose and duration are two of the top independent risk factors for corticosteroid side effects. So as clinicians, how do we mitigate that with injections? One option is to space the injections out. The other option is to minimize the dose. Many of us use three-month intervals at minimum between corticosteroid injections, as is a common practice. This has actually been studied and shown that certain side effects of steroids, like OA progression, are minimized, if not mitigated or eradicated, by using this three-month interval spacing. So at that point, we know, roughly speaking, three-month intervals between injections is well-studied. And at least that's a good common practice. So the next step is we need to agree on dose. When you look at the data for other common corticosteroid injections, like epidurals, and the study that I'm actually citing here was an AAPMNR study, there is a global discordance in agreement, not only for SI joint injections, but other common corticosteroid injections, reflecting a greater need to analyze this. Lastly, the fact that our study suggested that females have less pain resolution than males with this intervention was kind of mirrored in other studies and kind of not. When you look at other, like RFAs, other studies analyzing how the change in pain is related with sex for procedures like RFAs and other pain interventions, some studies said, yes, it does play a factor, some didn't. And ultimately, the data is inconsistent. This needs to be analyzed more. So in conclusion, there is no dose-significant change in pain in our study. Additionally, from this, we need to advance our inter-articular dose discussion so we can better choose what dose is optimal for the patient in front of us. How do we do this? Well, we need more large perspective trials, gathering more evidence and more data so we can ultimately create evidence-based guidelines. Thank you. Thank you. I have some questions. So the amount of pain relief assumes that the SI joint is the appropriate pain generator. So was there any look at the workup to assess whether it be physical exam or some other? Yeah, so all of that's actually a great question, something we have discussed. All of the cases that we've looked at actually a great question, something we have discussed. All of the cases that we selected for these SI joint injections were evaluated by board-certified physiatrists in the same academic center. So there was pre-exam concordance and decisions. And there's a uniformity in terms of the provider's training or practice that they practice under prior to being selected for injection in the first place. Because I agree that's a challenge, if you will. Is this actually even the right generator? Not that I'm aware of, it was in terms of our study and our data, we really just looked back at the data from pre-procedure and then the day of follow-up. And was there a consistent or standardized follow-up for these procedures? No, but typically with our scheduling it's about four weeks, hence the 31 days of follow-up. So four weeks is a long time to follow-up after a corticosteroid-based injection. I just wonder if there are any variables that the patient has, recall bias or something else? 100%. Yeah, and that is something I kind of question myself at 31 days. Could they have recall bias? Could something else happen to generate further pain in the area too? So there is a definite some confounding there. So basically you guys were just looking at the pain score and that's no, any correlation to it? One of them, are these contrast-enhanced injections, and second, do all of them go in the inferior border of the SI joint, or do they enter from different angles? You know, from provider to provider, I'm not 100% sure, but I believe with our institution, we almost entirely use the inferior border for this with contrast to confirm. Did you look at the potency of other codex steroids that may be used, you know, triamcinolone, dexamethasone? Not for this study. We just focus on methylpropanethasolone to kind of keep it uniform, to help with that, but that is a good point. Did you look at the European literature? What are you citing? Like, any of the Europeans, the British version of JMJS. I did not find anything. Any of the Asian stuff, you know, where you don't do it in a vacuum. So I actually went and did a little bit of a rabbit hole search, looking at societies like American College of Rheumatology, and all these other big societies, too, and they endorsed, like, yeah, it's a great idea, but then when you look at the doses they recommend for X joint, it was like 10 to 60 of steroid Y, but there was like a factor of six differential in that. So, and they, within those kind of guidelines, they didn't actually cite other sources that I could find that were really guiding even those. So it was more of like an expert panel with those guidelines. And then you can even, from there, go, like, well, how bad is the pathology within the joint? Because was it, would the pathology coupled with X, Y, and Z, are they metabolized or faster than others? Like, there's a lot of, this is a tip of the iceberg kind of study because there's so many different ways you can dive into it from there. To study some more. We're all learners. From like a simplistic standpoint, like, my conceptualization would be to, all right, if 40 works better, works as good as 80, what if we cut it in half? And then from there, if 20 is not as good as 40, and we're just going to focus on methylpenicillin first, then what's the difference between the two, or how do we start stratifying? Maybe 20 is better for BMI less than 60. We are in the Midwest, so we have higher BMIs, too. And so there's a lot of different ways you can go about this study, which I truly think is why there hasn't been a lot done guiding this. It's more clinical gestalt because you're kind of opening Pandora's box of exploration for something that is going to make, it could make clinical significance for certain patients, but it's a long route to get there. Question in the back. From what I remember yes, but I do not have a hundred percent like site some sources like that Like a control Make sure what's actually saline versus that lighter came versus marking so Because like we didn't call the patient the next day to see actually the good results the next day It would have been a good a good control for the study, too Just another add-on again buddy great job, I'll just put a little plug in at our Institute, Michigan We've implemented a learning health system to try to take some of these questions and this data turn it into discrete information So that pushing out some of these outcome measures will be pushing out the global impression of change and that will make things really Systematic so that we are getting those things at the two weeks or four weeks Whatever we set things out and we can really take a look at a deeper dive into these procedures And you know, we'll be able to take a look at these things from a ones and zeros standpoint I would advocate for everyone to start thinking about doing that especially for a lot of these procedures Awesome. Thank you It's really important that we have common variables that we're looking at so that we can pull our data and really get better Idea of what's going on? First off buddy just a awesome job man. Congratulations. You're a you're a rock star for this and for all the other stuff you're doing So early in your career, it's pretty amazing The so being a U of M person myself, I guess the question I had so you had no You know difference between the dose that was done with follow-up at 31 days But I think we probably have the ability like within the data set if they're generally done every three months Does the dose matter for how long the effects work So if you're not just looking at 31 days like if you could see their pain score when they're coming back three months after the fact for the next injection and You do that, you know We might have the data for that that pre pain score that would just be something else to look at where maybe it doesn't Change the pain, but maybe it changes the duration of how long it lasts great point Well, and one of the other things to consider is what are they been doing in that 31? Lido. How much? Is it the same for both? I think it was 2 or 2%, but it was a one of one. I'll let the interventionists in the room talk about it. So something I actually want to add, too, about future practices, where we're going with this. Something from the study that I came across in my research was the fact that we commonly think young, healthy people can get away with more, maybe less. They can metabolize and tolerate steroids better. I actually found a study, it's a European study looking at athletes. I don't know, there's a mix of different steroids that they received, but the run of the short of this study is that at 14 days, these athletes still had, and it was only about 30, at 14 days or longer, they still had HPA axis suppression. So we're not only looking at pain relief with this, but there's other extrapolations from the study, too, I think are really crucial. If dose and duration are the two biggest things that affect side effects of steroids, we're looking at pain for this study specifically, but future studies, if an athlete gets a steroid injection of 40, and we say, all right, you're feeling better, go back out there, and they tear their ACL or something or they need this adrenal boost and their HPA axis is suppressed, that could send them off into adrenal crisis. So there are tons of different avenues where this study can really take medicine, and that was kind of the point of this, too, was to say, hey, how do we better analyze and how do we better guide our care with our patients? For the degradation of the joint itself, I actually found a study. It was radiologists guided, and they did Q3 month. I'm sorry? I think it was, I don't know if they did, I think they did x-ray, not CT for the, well, the imaging was a fluoroscopic guided procedure, so it was SI joints. But they used x-rays to analyze SI joint pathology and compared a patient population that got nothing, like they got no injections over three years, versus those that got Q3 month scheduled steroid injections. And there was actually no progression of OA between the twos, no difference, but those that received the steroids did have therapeutic benefit from a pain standpoint. So from a joint degradation, that's kind of what I was briefly citing with that three-month interval. We're okay there, we believe, based off of other studies, but even to your point, like, how long? Because this was about a three-year study for that one. Well, and at what point do you keep doing SI joint injections and go to an RF? Right, well, if that's covered too, but that's a whole nother, yeah. I just had a question, mostly for the practitioners here, because I've seen it done both ways, and the reason I asked about the volume is just having more chondro, like if you're using, if you're replacing the extra CC with lidocaine, is that more chondrotoxic? But I've had some attendings that just. Really confounding variable. They'd feel better. But treating the patient feels a lot better. I'd feel better. It's not a scientific response, it's more, let's just treat the patient's pain. Well, and it's always a struggle. So let's treat the patient's pain and give them a bunch of Oxycodone, they're happy. Is that because the OA might be more mild at that? Because that's been the orthobiological foundations and some of their stuff they say like mild OA is more likely to respond. So is it their age or is it the pathology? You know, one other thought is, you know... All right, we're off to our final presentation by Dean Wondrek. Differential expression of micro RNAs associated with opioid use in spinal cord injury. Okay. Good evening, everybody. It's nice to be here. My name's Dean Wondrak. And I'm Catherine Weir, and we're both third-year medical students at the University of Minnesota Medical School. All right. So, our project that we have here, we're kind of exploring the differential expression of microRNAs with patients who've been used opioid medications in the setting of spinal cord injuries. So, just to give a little shout-out, we'd like to thank all the people who helped get us here. Shout-out to Dr. Leslie Morrison-Winn for helping us do the project. And also, we'd like to thank the University of Minnesota and the PM&R Department for helping us come here. So, one of the things as a medical student that I've noticed on my PM&R rotation, and I'm sure most of you all have noticed this in the hospital or in the clinics, is how difficult the management of pain can be in patients with spinal cord injuries. Research suggests that over 80% of patients with a spinal cord injury experience pain. Around 58% of people would classify that pain as excruciating or very severe. And we just had a lot of really amazing conversations about really procedural-based pain strategies, which was great to hear. But another pain medication that's frequently used is obviously opiates. One study found that 44% of patients who have a chronic spinal cord injury are on an opiate medication for pain. With, like, new literature coming out every day, there's been a lot of literature suggesting that opioids kind of inhibit several key processes within the nervous system for repair and recovery. And the correlation that we kind of found in our data suggests that maybe microRNAs are playing a role in that pathway. or inhibition of translation and microRNAs have not been previously well understood and their clinical utility and applicability had not been explored extensively, however This is really at the crux of our desire to further this research project and to explore through this lens of microRNA expression to see if there is a distinct relationship between expression in patients with spinal cord injuries who do and do not use opioid medications for pain relief. And just to pull the room really quick, who is familiar with microRNAs? Raise your hand. Okay. So, you know, we have a large array of learning on different levels, so we got to learn a bunch of procedural things. We like to share our research here. So there were a number of microRNA sequences that have been previously associated with CNS functions, such as synaptic potential and plasticity, and we received written permission from one of the key contributors to the research project for this graphic on the left here, which really illustrates some of the microRNA sequences and what CNS functions have been associated with in the literature previously. So we evaluated a broad range of microRNA sequences. With and without spinal cord injuries, and the data included in this project originated from three studies, two clinical trials, and one observational study in which baseline data was collected between 2017 and 2019, including age, sex, tobacco use, opioid use, acute versus chronic spinal cord injury, with acute being duration of six months or fewer for all patients. And then plasma samples were drawn from participants, processed, and analyzed to determine the concentration of various microRNA in the samples. Table one here better analyzes our participant demographics in further detail as well. So within these results, we kind of did two follow-up screenings, looking at these 30 microRNAs that we kind of discussed that have been shown really effective and involved within the central nervous system for various different processes. So first we ran a screening test that compared opioid use, and the second one we ran was based on like injury duration, if the patient had an acute spinal cord injury or if they had a chronic spinal cord injury. Then using various statistic methods, we kind of determined the differential expression based on a log two-fold concentration and using a p-value less than 0.05. We used linear models and applied all the participants' data along with the microRNAs differential expression to kind of get, to see if we can get an accurate picture of what these microRNA levels are. So of the 30 microRNAs that we looked at, two of them were differentially expressed based on opioid use. So our research examined models that both involved patients with spinal cord injuries and patients with and without. So model A over here shows patients with and without spinal cord injuries, and model B shows a spinal cord injury-only model. Ultimately the models were similar, but the spinal cord injury-only model kind of revealed some more variance in the microRNA levels. This kind of suggests that microRNA regulation mechanisms within the body might be a little bit more pronounced after an individual is exposed to some traumatic or neurotrauma. So this is a really important hypothesis that future literature is trying to expand more on. So coming back to the results of our study, we found that microRNA 132B was significantly higher and expressed greater in patients who were using opioid medications compared to non-users, than microRNA 92B was significantly lower in individuals using opioid medications compared to non-users. Some other interesting things that we found in our study was that as pain severity levels increase, microRNA 132 increased as well, whereas 92B decreased. We also examined smoking status. We found a significant relationship between 132 and smoking status. This was kind of based on prior work that Dr. Morris has done. So after we kind of got these results and we found that there was this differential expression when exposed to opioids, the next big question is, okay, why is this important? So we used different tools such as MIR-based to try to find validated targets to see what these miRNAs are acting on. So today we're going to present a few of those validated targets that we find, just like a reminder that these are like preliminary results and recognition that further research must go on to see what exact target validation is occurring in order to better understand the effect that opioids are having on our patients. So these are some of the microRNAs and their validated targets that we looked at. One of the important targets for 132 is actually an opioid receptor itself, which is quite interesting. In research regarding zebrafish models, activation of this morphine on this receptor led to increased expression of 132, and that kind of served as a negative feedback model. So as 132 levels were upregulated, the OPRM1 receptor was downregulated. This kind of shows that maybe that this mechanism through microRNAs are playing a role in opioid tolerance and regulation. Another interesting protein that we looked at was MECP2. Importantly this protein serves as a inhibitor of brain-derived neurotrophic factor. Therefore research kind of found that as 132 levels went up, MCPT2 went down and BDNF went up as well. BDNF is a really important protein involved in neurodevelopment and cell regulation of plasticity. So kind of this background information is supported by different animal models who found that areas that had increased BDNF and exposure to these microRNAs had increased synaptic plasticity in brain regions important in addiction, such as the nucleus accumbens. One more important topic or microvalidated target that we'd like to talk about is MMP9. Inhibition of this protein kind of led to increased length and area of the dendritic spines. This research was also supported in other animal models which kind of showed mice with morphine dependence did have more structural plasticity in anatomical regions such as the dentate gyrus. Much of the prior literature discusses up We also want to take a moment to kind of briefly acknowledge some of the limitations of our study. First of all, the model that we had and the participant numbers with or without spinal cord injury is kind of low. So additionally, further research with a much larger and robust sample size would be really important. Additionally, this data is cross-sectional, therefore it's not really feasible to make 100 percent cause and effect relationship here. So kind of to wrap up this talk nicely, our research found two microRNAs that are significantly associated with opioid use in the setting of spinal cord injuries. We hope the results of the study will kind of serve as the foundation of additional research because this is a field of medicine and a field of the literature that's not really explored that well, with the goal of kind of helping develop better treatment options for this kind of patient population that's very medically complex. Thank you for listening. If anyone has any questions, we'd love to thank you. Thank you. Okay, I'll start off the questions. So spinal cord injuries are classic neuropathic. That's a really good question. I cannot say that it necessarily has. I'd have to double check with our PI on that, Dr. Leslie Morris. But it is a really good question, especially with these patients who have been on chronic opioids for a long period of time as well. There might be a more pronounced change in the regulation of these microRNAs. Well, and that's a good segue. So was the amyloquine dose of opioids studied? Because it was between three different studies. So that's kind of the data that was captured is based on three different populations. The main effect that we were kind of the results that we broke down was basically like a yes or no with they had opioid use or not. Obviously, the doses of opioids probably does have a great impact on this. And then this is something that I think would be really important to work up a little bit more in the future. And was there any look at sort of non-opioid adjuvant medications that were used concomitantly? There was not as well. But there is a lot of other medications that people are prescribed, like gabapentin, for example, if they're having a lot of neuropathic pain. But this was just a narrower focus kind of within the scope here. And it's a great, you know, I think. Additionally, one of the things that I think is really important and kind of like a next step that I want to take with this study is looking at the other medical comorbidities that might be present. You know, we're still third-year medical students, so we're still kind of deciding what paths we want to go down. So, I'm in the balance between like PM&R versus— PM&R. Yeah, PM&R versus psychiatry. You can't say that at a PM&R conference. I know. But I've enjoyed my time at PM&R so much. But one of the things that I find really interesting is like the psychosocial workup, especially with patients managing with depression, and one of the things I would like to explore is the co-founding variables, you know, between spinal cord injuries and depression, because one of our microRNAs that we kind of evaluated, this 92B, had increased levels of depression and anxiety associated with it. So if you choose to go into physiatry, you'll see that we go beyond the— So, if you like that approach, you know, sort of the biopsychosocial, you know, I was just trying to get the rotation on time third year medical school. This is just Smoking did what there? Yeah, there was a relationship between smoking status and Yes, personally I haven't we haven't kind of explored that Avenue doubt, but it sounds like that Yeah, so one of the things I think are really cool is the micro RNAs are kind of being developed as new drug targets. So I think there's around 10 phase three clinical trials at the moment that are kind of examining how these micro RNAs might be served as potential. Well, yeah, there's so many other variables that could play into that. Yeah, it's what happens on the bench and then what happens clinically, a lot of times you're two different guys. And it was really good to hear, like, a lot of really good, like, clinically-based, you know, research projects. We obviously acknowledge that, like, theoretically, if this, down the pipeline, maybe, like, 20 years from now, maybe this could serve as a foundational piece of literature for something, but this is definitely kind of new things that are being explored at the moment. Yeah. Thank you. I think it's important to note whether they're taking oral opioids or smoking their opioid. All right. Any other questions from the intelligent audience here? Yes, today's the opening reception, correct? Welcome reception. So it's downstairs in the exhibit area. So go in and talk and enjoy some refreshments. Save the day. And feel free to come up to anybody in the research committee to talk about your plan. Also, special shout out to Chris for saving the presentation. Yeah. Yeah. All right. We're going to keep up the good work. Yes, special shout out to Chris over here for saving our presentations. Shout out.

differential expression

microRNAs

spinal cord injuries

opioid medications

microRNA 132B

microRNA 92B

pain severity levels

smoking status

microRNA regulation mechanisms

opioid tolerance