All right, we got 8.02 on my clock, so let's go ahead and get started. So, hello everyone, I'm Nathan Katz, a member of the Education Subcommittee on the Medical Student Council for the AAP. Today, we got two really awesome speakers. Our first one is Alexander Rose, who's a third-year med student out of the St. George's University School of Medicine. He's going to talk to us today about pumenar and the treatment of transverse myelitis, a really interesting topic that I'm excited about, so I'll let you get started when you're ready, Alex. Awesome, thanks, Nathan. Let me just share my screen here really quick, and then we'll dive right in. All right, can you hear me all right and see the PowerPoint? Looking good, Alex. Great. So, before I start, I just want to thank the Medical School, the Medical Student Council of AAP, and Nathan for making this all possible. And so, as you can see, I'm going to talk about transverse myelitis and neuromuscular electrical stimulation and the treatment of it. So, first, I'm going to talk about some background knowledge on transverse myelitis, just to get our feet wet, and then talk about the journal article, and then some other common treatments. So, transverse myelitis is an immune-mediated injury to the spinal cord, and it causes weakness, sensory alterations, and autonomic dysfunction. And the thing that makes this unique is that it affects both sides of the same section of the spinal cord, and it also damages the myelin, such as in the name. And then neuromuscular electrical stimulation is a device that sends impulses to the nerves, and it causes muscles to contract. And this is very helpful treatment in transverse myelitis, and commonly used by physiatrists to retrain or re-educate the muscle to function and to build strength when you're not using it. So, really quick, if I can just have whoever has their phones handy to pull it out and then point the camera at this QR code, this will allow us to just take a few quick, short questions just to gauge previous knowledge or baseline knowledge on transverse myelitis. So, I'll give people a few seconds to take their phone out, if they have it handy. No biggie if not, and scan the QR code, then you can just press skip or type in your name, doesn't matter. And so the first question that you should see is, which of the neurological pathologies below is the most common on your phone? So here we see some options, multiple sclerosis, Lambert-Eaton, syringomyelia, ALS, and transverse myelitis. A lot of these are super common that you might have heard of from step one. I know they're a pretty high yield, multiple sclerosis was. So we'll see the answer is multiple sclerosis with 350,000 people affected in America currently, and then Lambert-Eaton, 30,000 cases a year, syringomyelia, 26,000, ALS is 7,000 cases a year with 30,000 Americans currently affected, and then transverse myelitis is only 1,400. So right here, we can see right off the bat, it's much, much decreased incidence compared to all these other spinal cord injury diseases. So this is kind of actually part of the reason why I'm interested in it is because it's rare, and so a lot of people might not come into contact with it. But when you do, I want us to have a baseline knowledge of how to treat it. I actually worked with a physiatrist a few months ago at the hospital, and we had someone come in, and he used neuromuscular electrical stimulation on this patient. So that was pretty cool. So the epidemiology and the etiology of it is that, as I already stated, you have about 1,700 cases per year, and it's commonly combined in the diagnosis of multiple sclerosis and neuromyelitis optica, which brings it all the way up to 24 million people if you include those other common diseases because they're so similar. And then it's associated with, like I already said, multiple sclerosis, neuromyelitis optica, and any viruses can cause it, as well as autoimmune disorders. So the pathogenesis of it, if you just want to look at your phones again, and then you should see the pathogenesis options of transverse myelitis, so on your phone. And so you have T cell media loss of axons, autoantibodies directed against presynaptic calcium channels, lymphocytes and monocytes infiltrating the cord, or antibodies against postsynaptic. And as we'll see right here, transverse myelitis is actually caused by the lymphocytes and monocytes infiltrating the cord with inflammation and demyelination, causing injury. And then multiple sclerosis, lambry and myasthenia gravis are the other common pathophysiology causes of those spinal cord injuries. Now it's so similar to multiple sclerosis because they both cause the breakdown of the spinal cord in similar ways with the myelin. However, transverse myelitis is at that same spinal cord level, while multiple sclerosis is patchy throughout the peripheral spinal cord, as well as the periventricular lesions. So there's a few diagnostic criteria, it has to be bilateral, it has to have a clearly defined sensory level, which separates it from multiple sclerosis. There has to be spinal cord inflammation evidence on imaging, as you can see here on this slide. And then it has to be relatively acute, it has to progress to the most severe form of the disease, or the nadir, four hours to 21 days after onset. And then you have to exclude all other causes. And that way, it's kind of a diagnosis of exclusion. So the symptom that I want to focus on is weakness. The physiatrist will be consulted for new or acutely worsening debility, weakness, impaired balance, poor endurance, bowel and bladder management, or spasticity management. The most consistent symptom, and the one that we saw with our patient also is the weakness. That was a teenager, he couldn't move his legs, and it was really scary. And that was his number one worry and priority. And electrical stimulation can help with this. So current physiatry guidelines show that exercise is the number one rehab form for recovery of transverse myelitis. However, when patients A, are unable to for any reason, even like such as weakness, or B, just don't have the motivation or can't, just aren't reliable patients to follow up with, that's when electrical stimulation comes in and can be really beneficial. Why is this so important? According to the PM&R board review, immobilization of the muscles can decrease the strength by one to one and a half percent per day with five weeks, and activity will cause 50% of the previous muscle strength to be lost. That brings us to our journal article that I wanted to talk about, which was neuromuscular electrical stimulation for muscle weakness in adults with advanced diseases. It's actually a meta-analysis looking at a ton of different studies, just because there's never been a clear, concise thought process on whether this is beneficial or how beneficial. So the title is at the top of the slides for those who are wondering, and so the objective of this was to evaluate the effectiveness of neuromuscular stimulation on the quads and muscle strength in adults with advanced diseases. So there are numerous publications outlining the benefits, as I already said, however, the exact benefits, the exact muscle strength increase, and further details were never really outlined. And so that's why they did this meta-analysis. And here's just a long list of the various sources that this meta-analysis took data from to combine. And selection criteria actually contained some spinal cord injury, but focused on chronic respiratory diseases, chronic heart failure, cancer, HIV, and AIDS, but the mechanism of weakness was from disuse, which is also the benefit that neuromuscular stimulation is studied on with transverse myelitis. So here's just a picture of a neuromuscular electrical stimulation device for anybody who hasn't been familiarized with this. So basically it's just a lightweight battery powered stimulator that has little self-adhesive electrodes and you can put them on yourself, and it's really easy to use, and patients can use it at home, which makes it very convenient and user-friendly. So the intervention was that people would, patients would, oh, sorry, I'm jumping ahead. So neuromuscular electrical stimulation can be used to produce muscle contraction. That's 20 to 40% of the maximum voluntary contraction, which I thought was actually kind of a lot. On the quadriceps muscles, it can be administered at home, unsupervised, which carries a low metabolic load because it's so light, so it would not cause patients to be getting extra workout from carrying this thing around, and that would help it not skew the data. Also, the last thing was that it's very convenient. Like I said, you can do it while reading, watching television, cooking. You can do NMES while you're doing other activities, which is also a reason why some patients might not do exercise just because they say, oh, I don't have enough time in the day. So this is where I jumped to earlier, jumping the gun, but the study was 30 to 60 minutes of stimulation on the patient's quads, and this would be performed three to five times a week for four to eight weeks. So right off the bat, you see there is a lot of variability that the patient can use it with the timeframe, which will hurt the results. But the data that was measured was two things, muscle mass measurement and then the strength, which I'll talk about in a few slides. So muscle mass measurement was always assessed using imaging or as volume or cross-sectional area. And the modalities were a DEXA scan, anthropometry, ultrasound, and a CT. And as I already said, patients were followed up to within four to nine weeks. So an improvement in muscle mass was observed following the program, but one of the studies or one of the groups of studies that this meta-analysis focused on, that focused on the volume, showed that it was dependent on the modality that was used. This is because there was no evidence of an effect difference using the DEXA scan or anthropometry to measure the mass. However, there were moderate to large effect sizes observed in studies using the ultrasound and the CT, which contained 95% confidence interval of 0.26 to 1.39, with the result being 0.82 with ultrasound. And the result for CT was with 1.01 centimeters cubed increase with a confidence interval of 0.42 to 1.60. So I'm going to show you a forest plot in the next slide. And just for a little refresher, I know I didn't remember how to read a forest plot. The horizontal lines is the 95% confidence interval of one study. And each line is an individual study with the odds ratio being the center dot on a horizontal line and then the diamond at the bottom being all the studies combined, which might be a little different because multiple studies gives more power favoring rejecting the null. So if a study crosses the horizontal, the y-axis, then it would be crossing the null, making it not statistically significant. So out of these 13 studies, there's only three that have a confidence interval or horizontal line that does not cross the null, meaning that the other 10 should be considered statistically insignificant. However, the diamond at the bottom is the mean, if you draw a line through that, that's the mean of all the other studies combined with the width being the confidence interval. And that is favoring NMES for a beneficial outcome and strength, which is good, however, the power of multiple studies makes us want to question this accuracy. So the strength that that forest plot showed is measured using dynamometry versus the previous studies that were looked at. We're looking at the volume of the muscle, this is looking at the strength, which is measured with this device. I don't know if any of you are familiar with this, but with the last 13 studies only showing significant difference when combined, this had 12 studies with 781 participants that were assessed with dynamometry. And compared to control groups, NMES had a significant improvement with a standardized mean difference of 0.53, which was equated to the ability to lift an additional 1.1 kilograms or two and a half pounds from the previous maximum weight compared to the controls who did not use NMES. So there's a lot of things that we could talk about, such as bias with participant bias. The participants knew that they were not the controls because they were using the NMES. The participants also had a lot of different options on whether they could use it for 30 minutes or 60 minutes. So there's a lot of variability, but as a meta-analysis, it's good to combine it all and kind of get a feel for how effective this therapy currently is. So the conclusion is that this review suggests that there is an elective treatment for muscle weakness in people with progressive diseases, such as respiratory disease, chronic heart failure, and it has increased strengths as opposed to not using the stimulation. However, the effectiveness still needs to be studied. There were numerous other studies that did focus on transverse myelitis in the literature, but it's very hard to give this significance considering there's only one or two cases that are observed because it's so rare. So in this research article with two case reports, NMES intervention for Guillain-Barre, which is very similar demyelinating disease to transverse myelitis, it causes weakness in the same mechanism, reported that intervention tended to inhibit muscle mass loss more than no intervention. It seems safe and feasible. So I think that's the thing we could come away with is that there are some benefits that are shown. It's safe, it's feasible, and it's affordable. So recovery, to some extent, is expected in transverse myelitis, but it is important to minimize the effects of the temporary impairments. So why you want to use electrical stimulation is because all these spinal cord injuries have a paralysis acute phase where they can't move, like my patient or the physiatrist's patient who I was working with came in, he couldn't move his legs. And then you have the recovery phase. Well, if you lose all that muscle mass during the paralysis phase, and that makes the recovery phase much more strenuous. So that's where neuromuscular electrical stimulation really comes in is to contract the muscles and use as exercise therapy during the acute paralysis phase when the patient's unable to move. Also, I just wanted to show this really quick slide. I know I'm running out of time. This is from the Physical Medicine and Rehabilitation Board Review of the numerous effects, beneficial effects that transverse myelitis has on patients and is advised for physiatrists to use currently. The treatment guidelines from PM&R Knowledge Now, just so you guys know, for your PM&R rotation, if you've not had it yet, to impress your attendings, first, it's always the ABCs, airway breathing, circulation, then you want to get steroids to decrease inflammation, which is always important, plasma exchange, because it can be, as we talked about earlier, it can be a immunosuppressive, it can be an autoimmune mechanism, and then immunosuppressive, which helps in the same way, and then a multidisciplinary rehabilitation program that the physiatrist is usually leading, which is really cool. Now, unfortunately, the outcome is varied. Some patients, so recovery, most remain with residual impairments, and then a small percentage have recurrence. Also, another tie-in with multiple sclerosis is it commonly leads to multiple sclerosis, and that disease begins with the acute transverse myelitis presentation. And really quick, some other therapies is technology, such as robotic-assisted gait training devices, such as the Locomat. I know there are a lot of other different companies that make some, but this is great therapy for transverse myelitis, just not widely available yet, and then the everyday therapies, such as wheelchair exoskeletons, smart home devices that can make everyday life easier, and then the last fun fact to impress your attending is the difference between neuromuscular stimulation and transcutaneous nervous stimulation, which is used for pain. So TENS is used for pain, and NMES is used for muscle contraction. TENS inhibits pain the same way that you would press on a sore really hard. It kind of blocks the nerve transmission at the spinal cord level by releasing dynorphin and enkephalin. I don't know if you remember that way back from med school, but that's all I have. Thank you. Sorry for talking so fast. I wanted to get through it within my time, and I would be happy to answer any questions. Awesome. Great job, Alex. And then, yeah, any and all questions, if you're okay with that, Alex, I'd love to see someone come on, either on mic or just get their video started if they want to ask some questions. Sorry for going over. You're okay, Alex. Don't worry. We started at 8.02, too, so you finished right on time. Awesome. A question that popped into my head was, is there, like, because, and it seems like it's more of an upper motor neuron-based disease, if I'm not mistaken, so does any of the other symptoms associated with upper motor neuron diseases cause difficulties with using NMES, or is it all helpful? It's actually, it's beneficial in most diseases with upper motor neuron pathology, just because it works directly at the muscle level. It doesn't require axon, it doesn't require action potentials to go up to the spinal cord and then back. So that's why it's so universally beneficial from everything from CHF to, you know, to transverse myelitis, I guess. Awesome. Thank you. Any other questions from the crew? Well, I guess that means that I did a good job of explaining it, so thanks for listening. Very thorough, Alex. Nicely done, man. All right, and then I'm gonna get you all prepped up and ready to rock here, Angela. I just want to make you a co-host. All right, you should be a co-host now, Angela. So let me give you your intro here, and then we can get you all prepped up and ready to go. Let me give you your intro here, and then we can get you all prepped up and ready to share your screen. So we got Angela Nwankwo, a third-year medical student at UMKC, and she is going to present a systematic review and meta-analysis of alpha-lipoic acid and the treatment of diabetic peripheral neuropathy. It's a mouthful, but really fascinating subject I'm interested in. So you can go ahead and get started when you're ready, Angela. Thank you. Awesome. Okay, so can everyone see my screen? I can. Okay, thank you. Thanks, Nathan and the AAP MSC for hosting this event. And Alex, your presentation was... Sorry, Alexander, your presentation was great as well. Thanks for giving that overview of the chart because I'll also have some of this featured in my presentation as well. So I will be talking about alpha lipoic acid and the treatment of diabetic peripheral neuropathy. I chose this topic because I'm really interested in integrative and alternative medicine, just as complementary treatments to what we give our patients every day. So I decided to learn more about the different options that we can use for treating diabetic neuropathy. And so to start off, I just have a couple of like board style questions and an overview of diabetic neuropathy. So this picture just tells us about what's going on. I'm sure most of us know the basics of how the neuropathy works, but basically you start off with healthy tissue, and then it undergoes diabetic, metabolic, and vascular conditions that cause change to the capillaries. And then the capillary damage leads to nerve damage and loss of sensation. This particularly affects longer nerves in the extremities, lower extremities specifically. Then you get injury due to loss of sensation. And then the loss of sensation and circulation leads to increased risk of infection, ulcers, and gangrene. Things we know in clinic while we do our pinpoint exam, tell our patients to wear white socks, and always keep track of what's going on below their feet. So this is our first case presentation. It's a pretty simple question, just like you'd see in your everyday, your old bank, I guess. But a 55-year-old man has had a foot ulcer for two months that has not healed. Physical exam shows a two-centimeter shallow non-healing ulceration of the left medial malleolus. There is symmetric decreased sensation in the distal regions of the lower extremities. He has a history of multiple UTIs resulting from difficulty in completely emptying the bladder. He is impotent. So which of the following pathological findings is most likely to be present in the peripheral nerves? So anyone can just unmute and blurt out the answer. I'm going to say B. Okay, so the correct answer is actually D, but B is close. So the correct answer is D, because the features of peripheral neuropathy are associated with diabetes, and both the motor and sensory nerves can be involved. And this will give you an idea of what's going on. The motor and sensory nerves can be involved, and this will come to play as an automatic neuropathy. But the examination will show axonal neuropathy and segmental demyelination. So I guess technically, B and D could be right. So difficulty in emptying the urinary bladder and impotence are a result of the autonomic neuropathy. And like I said, the longer nerves are affected first. So this explains why the lower leg involvement is why you have diabetic foot impairment with trauma and subsequent ulceration. So on the slide here, I have the top picture is the normal nerve histology, and then the bottom is what you would see in diabetic neuropathy. So you can see that the membrane around gets really thickened, dark, and you don't have as much of that axonal space around the nerve. So second case, a 56-year-old woman comes to the physician because of a two-year history of burning sensation in her legs. She has occasional sharp lancinating pains that shoot up her legs, and she's tried hydrocodone and acetaminophen that provides some relief. She's had no weakness, headaches, confusion, or memory loss. She does have a 22-year history of hypertension, CKD, and type 2 diabetes with retinopathy and diabetic gastroparesis. Current medications include insulin, metformin, lisinopril, and hydrochlorothiazide. She has had an MI four years ago, and serum creatinine is 2.8 with A1C at 11.6. So which of the following is the most appropriate therapy for this patient's leg pain? I promise this one is not a trick question this time. Sorry about the last question. E, yes. Okay, so E is, and the explanation is just that chronic neuropathic pain can be difficult to treat, and a variety of mechanisms contribute to neuropathic pain, which is why we're going to talk about the different modalities, antioxidants that can be used to treat. And so the pathological reason behind why we use these first-line agents is because the primary nociceptors can get damaged, and they become highly sensitive to mechanical stimulation, and these generate impulses that happen in the absence or presence of stimulation, which is why they always have that chronic pain. And there's evidence that this is due to increased sensitivity and spontaneous activity of sodium channels, which is why we use TCA, zaloxazine, pregabalin. Many of these act at the sodium channels. Other ones that people use are carbamazepine, gabapentin, lamotrigine, and trimetol. Okay, so this is a summary of the study. So the objective of the study was to evaluate the effects and safety of 300 to 600 milligrams of alpha-lipoic acid given IV for diabetic peripheral neuropathy. And so this was a study done in China, so they just searched databases of different control trials of the treatment of ALA in diabetic peripheral neuropathy, and they were looking for the quality and characteristics of these studies. So the primary outcomes were the efficacy, and they measured this using the median motor nerve conduction velocity, which is just the speed of the signal transmission, and they did this for motor and sensory nerves in the median nerve and in the peroneal nerve. So they got an upper and lower limb signal. And the secondary outcomes were the adverse effects, so any side effects of using ALA long-term or in general in the body. So through their search, 15 randomized control trials met the inclusion criteria, and so the treatment group involved giving the 300 to 600 milligrams per day, and compared with the controls, the nerve conduction velocities increased significantly in the treatment group. And so they described the median weight differences, which ended up increasing over time in each of the groups, 4.63 for median motor nerve conduction velocity, 3.17 for median nerve sensory conduction velocity, 4.25 for peroneal motor nerve conduction velocity, and 3.65 for peroneal sensory nerve conduction velocity. All of these were in favor of the treatment group, showing that using ALA does increase the velocity of signal transmission when used for at least three weeks. So no serious adverse events were observed during the treatment period, and so in conclusion, they found that treatment with ALA is safe and provides improved velocity and positive neuropathic symptoms. But the evidence may not be as strong because most of the studies had poor methodological quality, which we will talk about at the end of the presentation. Okay, so these are our charts that Alexander helped us to go over, but basically we can look and see that only one of these ended up crossing the null, so most of them actually ended up being significant and showed improvement for favoring the treatment. So this is for the median nerve motor nerve conduction velocity. And then on the next slide, we will have the sensory nerve. So here we had about three of them cross the line, but still overall the majority of the studies were significant and showed a favor of the treatment of ALA and sensory nerve conduction velocity. Okay, so why would you use ALA for treatment in diabetes? So the main pathologic background for oxidative stress in diabetes is from increased free radicals or reduced antioxidant defense, which is shown in this picture. It's like a balance beam. You can have antioxidants that help, or you can have free radicals that kind of cause more damage. And the oxidative damage will affect the lipids, proteins, nucleic acids that all make up the nerve, and this can cause tissue injury and inflammation. So there's many pathways to oxidative stress. The main ones that are involved in diabetes peripheral neuropathy is the production of advanced glycosylation end products, the sorbitol hexokinase and protein kinase C pathway, the activation of poly ADP ribose polymerase. And I have pictures that we'll go over of these three pathways. It's a bit of more intense biochem review, but basically all of them have in common that they work with the glucose. And the end product of these three pathways is enhanced cellular oxidative stress, which ends up perpetuating diabetic neuropathy. So this is the advanced glycosylation end products. So the part we're really focusing on is how glucose, which is what we have a lot of in diabetes, ends up increasing advanced glycosylation end products. And then lipid peroxidation also increases these end products, which is where they're trying to have the ALA act at in this pathway. Here, this may be more familiar, the sorbitol hexokinase, hexosamine and protein kinase C. Glucose is acted on to get broken down into pyruvate. And then sorbitol also acts on glucose to turn it into fructose. And all of these pathways can contribute to diabetic complications with oxidative stress. And the activation of the poly-ADP ribose polymerase pathway, this one is mostly focused on cell death. So the PARP, that's the poly-ADP ribose polymerase. And so whenever it's inactivated, it can cause DNA degradation and apoptosis. And high levels of damage of the DNA can also cause necrosis. So it's like a multifactorial integration of all these three pathways that are suspected to contribute to diabetic neuropathy, which is why they have different antioxidants they use to try to minimize these complications. So like I said, the most common defect with diabetes is the reduction of motor and sensory action potentials. And so they estimate that the velocity is gradually diminished by about 0.5 meters per second per year. And that the use of ALA long term can slow down these degradative changes. And so basically, as any antioxidant works, it terminates free radicals, inhibits peroxidation, increases blood flow, and raises glutathione content of the peripheral nerve. So glutathione is also an antioxidant that acts to reduce cell damage. Another benefit of ALA is that it increases insulin sensitivity, although that effect was not studied specifically in this study, it is one benefit that people can attribute to using ALA in diabetic neuropathy. So it was first used in Germany to treat DPN, and they've had various control trials since then assessing its efficacy. And so here are some of the studies. Basically, the ALADDIN, ORPRIL, and SIDNEY trials, they all measured the same amount of ALA used, about 600 milligrams, and they just did it in different time periods to see how long it needed to be used to get its maximum effect. So with the ALADDIN study, they used ALA 600 milligrams over three weeks in the first part of the trial. And so using it short term, they saw that they got a long term response, and they did another trial, the ALADDIN 2 study, where they did the same thing, but added people taking twice the amount of 1200 milligrams, people taking the 600 milligrams, and then the placebo. And so then they studied these people for two years. And basically, they got the same results is that it's statistically a significant benefit of using ALA on nerve conduction after two years of treatment. The ORPRIL study was also a smaller presentation, a population that showed oral treatment with 600 milligrams for three weeks, improved symptoms and deficits from polyneuropathy. And then the SIDNEY trial was a parallel double-blinded study. It was one of the better conducted studies out of these three, showing that 600 milligrams infused IV for five weeks, five days a week for a total of 14 treatments showed a large benefit in diabetic neuropathy. So the summary of all these three were that ALA used for at least three weeks up to two years does show good effects in treating diabetic neuropathy, and that no adverse reactions are associated with the use of ALA. So safety analysis. So a big proponent of why people wanted to study antioxidant use for diabetic neuropathy was the favorable side effect profile. So compared to other first-line treatments like pergabalin and gabapentin for diabetes, which have a not super unfavorable profile, but more like dizziness, drowsiness, especially in the elderly population, antioxidants mainly had GI side effects, and that's only associated with very high doses. So they found that it's mainly a dose-dependent increase in nausea, and that happened after you went above 600 milligrams. Most studies only included 600 milligrams, so that's why they promoted that it had a favorable side effect profile. But as they went up to 1,200 and 1,800, they found that up to a quarter or a fifth and up to almost a half of patients had GI side effects. So they found that there is an oral dose of 600 milligrams once daily that provided the optimum risk-to-benefit ratio. And so overall, all the studies show that there was a good improvement of symptom relief, but their objective improvement in the nerve conduction velocity accelerations were a bit lacking. Sorry, I don't know why the video keeps moving across my screen. So overall, the treatment with ALA from 300 to 600 milligrams for at least two to four weeks significantly improves the conduction of median nerve and peroneal nerve motor and sensory conduction velocity. Treatment with LALA does not give rise to severe adverse effects, which is what makes it more preferable to other first-line medications like pergabalin and gabapentin. So some limitations of this study were that they had poor methodological quality. They did not always report the design, randomization, or concealment to randomization allocation. Most studies were of a small sample size, and the reason being was that not a lot of people wanted to try different medications because most people found that gabapentin and pergabalin are helpful for their diabetic neuropathy, so they weren't as open to trying new treatments. And whenever they did have withdrawals or dropouts, they didn't really describe whether they performed an intention-to-treat analysis. So in the future, if these studies are more rigorously designed and randomized, double-blinded, and have more placebo controls, we can better assess the effects of objective improvement in nerve conduction velocities. There are studies, however, in my research that I saw of them combining gabapentin and ALA for diabetic neuropathy and showing that using them together did provide a greater benefit in the treatment of diabetic neuropathy. So that's all I have. Sorry for the stumbling over my words. I haven't talked to people in a while, but thank you guys for listening. I'm open to any questions. Awesome work, Angela. And then, yeah, anyone who has questions, go ahead and jump on in. So this is actually really interesting to me because I also am a fan of... This sounds bad, but I'm also a fan of medicines that are more naturally found when comparing alpha-lipoic acid to pregabalin, for instance. But I was wondering if there were any other natural remedies that you found across your research that people could use. I saw some studies done on cranberry supplements, oral cranberry supplements, as a use for diabetic neuropathy. Those didn't really have any... They had improvement on patient satisfaction symptoms, but not really for diabetic neuropathy. Cool. Never would have thought cranberries. I have a question as well, I'm just trying to figure out how to phrase it. So have you seen, have you seen the usage of this in practice, especially because I'm just wondering like where this would fall in like the diabetes protocol, right? So you kind of alluded to it with the last statement you had, which is there's the one study that had a pen along with this being used both together, like synergistically. How do you see this used in clinic? Are they prescribing this or for every diabetic neuropathy out there along with standard medication or how do you see that going? So in my experience in clinics, I've only really seen complimentary treatments advertised by physicians that have experience in integrative medicine. I would say like on my day to day internal medicine clinic, I haven't seen it, but in family medicine, I worked with an integrative medicine doctor and she was very open to telling patients about different treatments and different things to add to their regimens. One thing she talked to patients about was like meditation for chronic pain. So I think it's very physician dependent. And then also if the patients do their own outside research and they say, oh, hey, can I take this in addition to what I'm doing, then that works. But I hope like whenever I practice, I can be one of those doctors that says, hey, maybe you can add this to your regimen in case you're worried about these side effects or I heard you're interested in this, you know. So I think it just depends on the doctor, because I feel like a lot of the pushback we get is, oh, this isn't studied or this is first line. We have to stick with this, so. That's true. Thank you. And that helps. I always like think back to like migraines, especially where they give them the whole like vitamin like surplus all in their face, like, oh, all this stuff helps. I think that's always a welcomed approach to physicians to have as long as there's obviously not pronounced side effects of being other comorbidities and whatnot. Very nice. Other questions we got for. All right, so I'm gonna wrap up with a few things here. We only have the two speakers tonight, so I wanna thank both of them again for coming on and giving us two really great presentations on two super interesting topics. All these were good and reminded me that I need to do some studying before I get back on rotations myself, with biochem and transmyelitis and all the jazz. So I appreciate y'all coming in and presenting for us. Just a quick announcements before we convene here. So Journal Club is undergoing a slight change in its format for starting next month. We'll still have three presenters, but we'll hit on specific theme topics in physiatry. Along with that, with a theme, we'll have an expert commission who will start to join us to weigh in on the clinical application of the topics presented. The next time we'll get together for Journal Club will be June 15th at 8 p.m. Eastern, where our presenters will tackle the topic of spasticity. And we'll be joined by our expert physician, Dr. Francois Betu, out of the Cleveland Clinic Physiatry Program. So a lot to get excited about for next time. And then for both of you who did a great job presenting tonight, if you wanna come on back, and this time we'll have a clinician present to help out with your presentations if you feel like coming back on and give it another go to present. Awesome, thanks. All right, and then I wanna just thank you all for coming and look forward to seeing everyone next time. Yeah, thanks for having us and see you next month. Thank you guys. Nicely done. All right, have a good night guys. You too.

transverse myelitis

neuromuscular electrical stimulation

muscle weakness

journal article

diabetic peripheral neuropathy

nerve conduction velocities

safety profile

insulin sensitivity