Hello back, everyone. So we're going to get started with our second session, which is going to be on primary endoscopic bariatric and metabolic therapy. So it's my true honor to introduce our first speaker of this session, Dr. Shelby Sullivan. She's the chair of the Association for Bariatric Endoscopy, my mentor and also a leader in our field of bariatric endoscopy. She has led multiple studies, several of which are pivotal studies that led to FDA approval that we're going to be hearing throughout this session. Dr. Sullivan. Hi, I'm Dr. Shelby Sullivan from the University of Colorado School of Medicine. Again, I would like to thank everybody for coming to this conference today. And I'm going to be talking to you about intragastric balloons, aspiration therapy and the trans pyloric shuttle. These are my disclosures. I do consult for a number of different companies, mostly in helping them develop their lifestyle therapy protocols for their device studies. And then I also have been involved in a number of research studies of the devices that I'll be talking about today. There are a number of intragastric balloons that have been studied in the United States. The Orbera intragastric balloon is a single fluid filled balloon that is endoscopically placed and endoscopically removed and was approved by the FDA in August of 2015. The Obolon balloon system is a swallowable balloon system. So three balloons are swallowed. They are filled with a nitrogen mixed gas, but also removed endoscopically. This was approved in September of 2016. Then we have two other balloons that are still pending FDA approval. This is the Ellipse intragastric balloon by Illurion. This is a single swallowable balloon filled with saline. It self deflates and passes naturally. This trial has been completed, but it's not yet approved by the FDA. The Spatz 3 balloon is a single endoscopically placed balloon that's filled with saline and adjustable. And it also is removed endoscopically. This trial has also been completed, but is not yet approved by the FDA. The Reshape intragastric dual balloon is a two balloon device that has two balloons, which are joined by a flexible shaft. They are filled with saline. It was placed endoscopically and removed endoscopically. It was approved by the FDA in July of 2015, but it's currently no longer commercially available. It was not removed from the FDA because of any safety concerns. It really was just based off of no longer being commercially available. The Orbera intragastric balloon, again, is available in the United States. It's a single balloon that is placed endoscopically or via transoral delivery. It is inflated under direct visualization with an endoscopy, as you can see in this video of the animation of an actual placement. It's filled with 400 to 700 milliliters of fluid, but on average, most people are filling between 550 and 650 milliliters. Using methylene blue to dye the saline is considered off-label use, but we do that so we can tell if there's a deflation. The patient's urine will turn a blue-green color. For deflation, we go back down with an endoscope. We pierce the balloon. We aspirate all the fluid out and then remove it endoscopically. And that's done six months after initial placement. And it's indicated for patients with a BMI of 30 to 40 kilogram per meter squared. In terms of indications and contraindications, these are some of the indications and contraindications. This is not an all-inclusive list, but includes some of the major highlights. So it's, again, indicated for patients with a BMI between 30 and 40 who have failed lifestyle therapy alone. Contraindications include prior foregut or bariatric surgery. And I would say that this is a really complete contraindication. Inflammation of the GI tract or ulcers, structural abnormalities of the esophagus, varices or cirrhosis, hiatal hernia greater than five centimeters, patients who are on aspirin or other anti-inflammatory or anticoagulants, or motility disorders of the GI tract. And I will say that this has been studied in an end-stage liver disease population who need weight loss before listing for transplant. But this is still listed in the FDA summary of safety and efficacy of the device. That is still listed as an exclusion just in general for a general population. So it is not clinically approved for that. In terms of clinical considerations, I usually test for H. pylori in these patients to make sure that they don't have another potential cause for ulceration. Consider avoiding in patients with possible delayed gastric emptying because, as we've heard earlier, this can, this balloon, one of its mechanisms of action is actually causing delay in gastric emptying. Consider avoiding in patients with moderate to severe GERD who may not be completely controlled with medications at baseline. And it will also cause significant accommodative symptoms. So you do need to tell patients about that. You want to prepare them so they can take some time off of work and give them prophylaxis. And I usually give a scopolamine patch, a prepotent, undansetron, hyosinamine, lorazepam and a pain control if needed. I usually give IV fluids during the procedure. And I usually give two liters of lactated ringers, decadron and undansetron to help control that nausea after placement of the balloon. And then we put them on a prolonged clear liquid diet for 24 to 48 hours and then full liquids until day 7 to 10 to make sure that their symptoms are under control before we advance their diet. The Obolon balloon system, again, is a swallowable gas filled balloon system. So there is a balloon that's contained in a capsule that is swallowed. There's a navigation system that uses electromagnetic features in order to follow the balloon into the patient's stomach where it's then inflated with the dispenser. And there are three balloons that are placed over time. Each one of them contains 250 milliliters of a nitrogen mixed gas. And I'm going to show you a video here. This is what the console actually looks like when a patient swallows a balloon. So the patient just had the capsule that got through the upper esophageal sphincter. Now it's going through the esophagus. And the patient is standing in front of a field generator and has a marker at their xiphoid process that correlates with the marker that you see in the middle of the screen. And you can see that balloon is still in the midline. It's still going down the esophagus. And right now it's transiting into the stomach. So it's coming off of that midline. And you'll see in a second that the patient is going to take a deep breath in. And that capsule that contains the balloon will go down with that breath as the diaphragm. There we go. As that diaphragm flattens out. And then we'll come back up. So we know that that balloon is now in the stomach and is out of the esophagus. And this new navigation system allows for placement without the need for fluoroscopy or digital X-ray. And it really does allow for this dynamic visualization of the capsule transit. This balloon is still removed endoscopically at six months. This is a picture of what it looks like actually in the stomach when you're removing these balloons. So they do take up space. But they're really fitting kind of in the same sort of configuration as the stomach itself. In terms of patient selection and indications and contraindications, again, we have an FDA-labeled indication of a BMI of 30 to 40. Failure to lose weight with lifestyle therapy alone. And then contraindications and anatomical abnormalities that inhibit swallowing. So patients really do have to be able to swallow this capsule. Prior surgery of the GI tract that may inhibit passage. Prior bariatric surgery. And again, that foregut surgery still applies to this balloon. Do not place this balloon in patients who have had prior foregut surgery. Inflammatory diseases of the GI tract or ulcers. Use of NSAIDs, other gastric irritants or anticoagulants. Untreated H. pylori infection. For this balloon, any hiatal hernia greater than two centimeters is really a little bit too big for this device. So in terms of clinical considerations, again, patients have to be able to swallow the placebo capsule. So there is a placebo capsule that comes with the purchase of any of these balloons. And patients can practice swallowing this capsule. But that capsule just contains some sugar in it. So it will dissolve and it won't be long-term stuck anywhere. But if a patient can't swallow that capsule or if it feels like it gets stuck in their esophagus, this is probably not the device for them. They must be able to come back for three balloon administrations. These balloons cannot be administered all in one visit. So they have to be able to come back multiple times. We also have to comply with travel restrictions. So patients must live within 4,000 feet above or 2,500 feet below the place of administration because this is a gas. And so barometric pressure does matter, which means your altitude matters. If the balloons are placed greater than 2,500 feet above sea level, patients can only spend up to three weeks at sea level at a time, but then would have to go back to elevation within that three week period in order for the balloons to maintain their integrity. Patients can't scuba dive and you can't fly a non-pressurized aircraft with this device in place. Accommodated symptoms are significantly more mild, so we don't in general tell people to take time off of work. In fact, when I place these balloons, patients normally go to work that same day. We only use ondansetron and hyosiamine to control cramping and nausea symptoms. And patients are only on liquids for 24 hours and then they advance to a regular diet. So this is a comparison of the intragastric balloon pivotal trial data in the U.S. And I am including Reshape in this slide, even though it's no longer approved for use, because I want to be able to discuss a little bit and review the effects of study design and its effects on weight loss. So both Reshape and Ovalon, which are two different kinds of balloons, again, a fluid filled balloon and a gas filled balloon, they both underwent randomized sham controlled studies, which meant that the patients did not know what groups they were in. And what you can see is that weight loss is very similar in both of these studies. So 6.8 percent total body weight loss for Reshape, 6.6 percent total body weight loss for Ovalon. But there's significantly more weight loss with Orbera, which was 10.2 percent. And we believe that this is related to the study design itself and that in general, randomized sham controlled studies, not just with intragastric balloons, but with other endoscopic bariatric therapies as well, results in lower weight loss in the active arms, in these randomized sham controlled studies than what we expect to see in clinical practice and in open label studies. However, the serious adverse event rates do really are a little bit more closer to what we see in clinical practice. And the serious adverse event rates for the fluid filled balloons were higher, 10 and 7.5 percent. But these were largely driven by accommodative symptoms. So nausea, vomiting, dehydration that required IV fluids. And we just have a lower rate of those kinds of events with Ovalon. So a significantly lower rate of serious adverse event of 0.3 percent. And again, this goes back, this slide really looks at those differences between active, between knowing whether or not you have a device and not knowing whether you have a device. So in the blue bars, we see the weight loss in the randomized sham controlled studies or the open label studies, but the randomized controlled studies in the U.S. for Reshape, Orbera and Ovalon. And in the red bars, we see clinical case series. So for Reshape, we see about 11.2 percent total body weight loss. Orbera was a little higher than that, close to 12 percent, about 11.8 percent total body weight loss. And Ovalon was about 10 percent total body weight loss. But you see that there is a significant difference in the clinical weight loss and clinical practice compared to what we see in the randomized, in particular, randomized sham controlled studies. In terms of these registry adverse event rates, there were higher serious adverse events with Orbera compared to Ovalon. Ovalon had a significantly larger number of patients in their registry series, prospective registry series of 1,343 patients that were included. So only a 0.15 percent incidence of serious adverse event. Orbera did not report on pain or nausea, but Reshape had significantly higher nausea, pain and vomiting compared to Ovalon. Again, going back to those reduction in accommodative symptoms related to the gas filled balloon compared to the fluid filled balloons. There was an early removal rate that was highest for Orbera, but still a 10 percent rate in Ovalon. And again, remember, if patients move with Ovalon, those balloons do have to come out if they're changing altitude. Deflation rates occurred at one and two percent for the fluid filled balloons, but 0.18 percent for the for the gas filled balloon. In terms of the non-serious adverse event rates that have been reported in these pivotal trials, we see that vomiting occurs significantly more often with Reshape and Orbera. The other things to point out is that gastric ulcers did occur in the Reshape study. But when they modified their device, that dropped down to 10 percent. We also see that GERD or reflux occurs in a higher percentage of patients with Orbera than they did with either Reshape or Ovalon. So something something to think about, again, when we're going to actually place these devices in patients. In terms of the Orbera post-market approval study, so this is really looking more approximating what we see in clinical practice. There were 284 patients enrolled, 258 started the study. Their BMI was very similar to this actual study, and that included a BMI of 35.1. You can see the age. And again, most of these patients in complete agreement with the randomized controlled trials. Most of the patients who are getting these devices are women. Failed placement in eight patients, early removals in 47. But they had study completion of 234 patients despite early removals. So the large percentage of patients actually completed the study, which is really to be commended. Serious adverse event rates did occur in 8.9 percent of patients. So similar to what we saw in the randomized controlled study in the United States. But again, these were mostly accommodative and they got 12.5 percent total body weight loss at six months with 8 percent total body weight loss at 12 months. So we still see a little bit of weight regain, but most of that weight loss is maintained. That's also true for the gas balloon. This is data from the randomized controlled trial in the US. Again, this was a randomized sham controlled study. And what we see is that there is significant weight loss maintenance, almost 90 percent that occurs between month six and month 12. So most of that weight loss is actually maintained. Glucose and triglycerides also improved and were maintained at that one year. Other studies that have looked at long term weight loss. This was a study looked at 500 patients with weight loss. And what happened at five years. So at balloon removal. There were 474 patients who were considered successful and they had more than 20 percent excess weight loss, which in this population was about 10 percent total body weight loss. At six months, we see that most of those patients are maintaining that weight loss. So that's six months after removal at 12 months after removal, 50 percent of patients are maintaining that weight loss. And even out at six, 60 months or five years after removal, we see that about 195 patients which were included in this analysis. We had a significant number of patients, about 25 percent of patients that were maintaining a percent excess weight loss of greater than 20 percent. We also looked at this with the ASGE and the bariatric task force, and this included a large number of patients in a meta-analysis. And three months after removal, we had a weight loss of 12.3 percent. At six months after removal, 13.2 percent essentially. And at 12 months, 11.27 percent total body weight loss. So again, we're seeing that this isn't the same as medications. That weight loss maintenance occurs with after balloons are removed. What about repeated balloon therapy? So this study looked at patients that were randomized to have either one balloon placement or have a second balloon placed one month after the first balloon was removed. And in that group B, in the green bars, you see that between month six and month 13, that there's even more weight loss. So what that tells us is that if you responded to a balloon the first time, you'll respond to a balloon again the second time and have more weight loss. They did regain weight over time, but with that two balloon placement at 37 months, you see that the weight loss was similar with the one balloon weight loss at six months. So again, what this really tells us is that there is some weight loss maintenance, regardless of whether you have one or two balloons, but that if you respond to one balloon, you will likely respond to a second balloon and get additional weight loss. We also looked at the difference in weight loss across BMI. So although the FDA indications are between a BMI of 30 and 40, off-label use would be considered any BMI outside of that range, but it's not contraindicated. It's just considered off-label use. And if we look at the data, even up to a BMI of 70, we see that percent total body weight loss is essentially the same, regardless of what your BMI is. It's really important, though, to tell patients, though, that they shouldn't expect bariatric surgery level weight loss. They really need to expect balloon level weight loss, but could achieve that regardless of whether their BMI is 31 or 45. There have been updates to physicians from the FDA regarding mostly the fluid-filled balloons. There were events that were not seen in the studies, including pancreatitis, hyperinflation, and deaths. And it's important to remember that the FDA has to put these things out if there are events that are noted that didn't occur in the randomized controlled trials. There were a total of 12 deaths, seven inside of the U.S., and at least half of those deaths were related to gastric perforation. So it's just important to remember all of those kind of safety features and the things that we would potentially not place balloons in patients that may have gastroparesis at baseline or delayed gastric emptying, or have a history of prior foregut surgery. All right, we are now going to talk about the SPATS Adjustable Intragastric Balloon. Now, this balloon, again, is a little bit different. It is placed endoscopically, as we can see in this animation, and filled under direct visualization, but it has a higher range of variable fill from 300 to 900 milliliters of saline plus methylene blue. It also has a 10 centimeter retractable stretchable silicone inflation tube that has a four millimeter outer diameter. And this allows physicians to either, during an endoscopic procedure, pull that catheter out through the patient's mouth, and either remove fluid if the patient is having symptoms and needs fluid removed in order to reduce those accommodative symptoms, or to put more fluid in if the patients are getting inadequate weight loss. And then the retractable stretchable catheter goes back into the stomach and the balloon stays in place. It's endoscopically placed and was endoscopically removed at 32 weeks in the U.S. trial. And again, that adjustability can occur any time during balloon implantation. This balloon is not yet approved by the FDA, but there have been a number of studies that have been done outside of the U.S. with previous generations of the balloon. And we see that weight loss is somewhere between 15.7 kilograms to 20% total body weight loss. There have been some serious adverse events as noted here as well. In the U.S. pivotal trial, again, this was an open label study. So remember that as we're evaluating this data. There were 288 patients with a BMI between 30 and 40 with 187 patients treated in the device group. There were downward adjustments in 28 patients and upward adjustments, which were not listed in the abstract, but increased weight loss by 4.7% after week 18, so we think at least there were some patients who had, there were definitely patients who had upward adjustments. Weight loss at 32 week in the device group was 14.9% and in the controls was 3.6%. Weight loss maintenance of at least 40% of the weight lost at week 56 was occurred in 75% of patients, so a really high percentage of the patients were maintaining their weight loss. Serious adverse events occurred in 5.3% of patients and ulcers occurred in 4% of patients. All right, we're not going to talk more about the ellipse balloon because that is a swallowable passable balloon, so even though it's an intragastric device, that will be reviewed in depth by my colleague Dr. Shariah in a later talk today. So we're going to switch gears to the Aspire Assist system. Now this is similar in concept to a percutaneous endoscopic gastrostomy tube. Patients aspirate gastric contents 20 minutes after a meal, two to three times a day, and it removes about 20 to 30% of the calories that are consumed at that meal, and we'll talk about that in a minute as well. But that still only accounts for 50 to 80% of the weight loss that was achieved in the studies. Lifestyle therapy and mealtime behaviors reduce overall food intake, and patients will actually tell you this. So in order for food to fit through the tube, and we're going to look at panel A here, the inner diameter of the A tube is only six millimeters, so food particles have to be five millimeters or less to reliably fit through that tube. That requires patients to chew like they have never chewed before in order to reliably get all their food particles that small. So patients will tell you that because they have to chew so much during a meal, that they just get tired of chewing and tired of eating, and so as a result they eat significantly less than they did prior to having this device. The other thing is that food choices improve anecdotally. You can see in the lower panel that the connector line and the drain tube, they are actually clear, so you can see what's coming out, and unhealthy food really does not look very appetizing coming out, and that really causes patients to make healthier food choices. So it really helps patients to cue in to what they're actually eating, and it's approved for patients with a higher BMI than for the balloon, so a BMI of 35 to 55. In terms of patient selection, and again, these are the FDA labeled indications and contraindications, and they are by no means completely inclusive. A couple of things that I wanted to point out is that you do have to make sure that you can place the device, and it's placed using a pull peg method, so it's a method that we use for placing other feeding tubes in patients, but patients do have to have the ability to have that placed. If we wouldn't be able to place the tube safely, then we can't place it in these patients. If they have a history of refractory gastric ulcers, that may be also something that you would avoid placing this tube in. Patients who have an eating disorder, bulimia or eating disorder, that is also a contraindication, and if patients have severe organ dysfunction, in particular if you're talking about patients who have cirrhosis and have any kind of ascites, placing a peg tube would be difficult, and so placing this Inspire tube would be difficult in those patients as well. In terms of clinical considerations, you have to talk to patients about time. They need to have the time to aspirate, and if they don't have the time to actually aspirate, this therapy is not going to get them much weight loss. It's a very active therapy where patients really have to do the therapy in order to get weight loss. Again, only works if they're really using the tube. In terms of eating behaviors, if you don't feel comfortable screening patients for eating disorders, send them to a psychologist. I use the question on eating and weight patterns, the fifth version, as a screening tool in my clinic, and if there's any suggestion on that screening tool that a patient might have an eating disorder, I refer them to a psychologist or a psychiatrist for diagnosis. In terms of long-term care, you do need to discuss the costs moving forward. We have a one-year package that patients, because most of these therapies, again, are not covered by insurance, so we talk to patients about that first-year package, but what are the ongoing costs after that? There are pieces to the device that actually have to be replaced and do require additional costs after that first year. In terms of a tube placement, we mark the breast lines and any bends in the abdomen while the patient is in the seated position, so we don't put this tube into a place where it's going to be rubbing up against something. We do give a prophylactic antibiotics, just like we would for patients who are getting a feeding tube, but we give additional antibiotics after that for the first 24 hours. We do use monitored anesthesia care at my location to place these tubes, but we don't always do general anesthesia. We usually just do monitored anesthesia care. We do give treatment for pain and for nausea, so oral acetaminophen, low-dose narcotic, and tramadol. I do give gabapentin after a few days of pain process because I find that narcotic pain medications don't do really well to control the pain after the first couple of days. You know, you're pulling that tube through the abdominal wall and we can't see nerves that we might be butting up against, and it's possible that it's that kind of a pain that's really causing more of an issue, and again, gabapentin seems to take better care of that pain in the short term after those first 72 hours. I also give Zofran or Ondansetron during the procedure and also give an oral prescription after that, although most patients don't have a lot of nausea after placement. I tell patients no showering for 48 hours, keep the site covered during during showering from day three to day seven, and clean with soap and water. We want to keep that site nice and clean. In terms of conversion of the skin port, it's actually very easy to do, and both nursing staff and my study coordinator during these trials was able to do this. We usually perform this one to two weeks after A2 placement, so that allows time for the tract to heal and reduces overall swelling. Remember, these patients have more tissue than a typical patient who is needing a feeding tube. They have more tissue that we're actually pulling that tube through, and that will swell and then go back down, and you want that swelling to go back down before you actually place the skin port because you want to place the skin port as close as you can to the skin without causing too much tension. I usually place the tray. You can see that we had just put the tray on, we cut the end of the tube, and now we're putting the cut we put the cutting tool on, and that all snaps into place, but I usually place that tray while the patient is in the seated position. In this video, this patient had, this was a A2 exchange, so this patient had already had the A2 in for a long time, and the reason why I do that in the seated position is that's when there's going to be the most tension on that tube, and then I have the patient sit up and lie back down two or three times to make sure that a tray is in position correctly before I cut the tube because there's really no going back. What you can see is that I put the backside of the skin port onto the tube, and I've put the blue sleeve, and that just helps to exert force onto the tube to hold the skin port on, and now I'm putting the top of the skin port onto the bottom of the skin port and snapping it in place, and that's it. That is how easy it is to convert an A-tube. All right, so now getting into the actual aspiration part. We did, as part of our pilot study back in like a 2010-2011, we really wanted to figure out how much weight loss was because of removing calories and how much weight loss was because of mealtime and behavior changes, and so we had patients eat a meal that was prepared by our bionutrition kitchen at Washington University, and then we had an identical meal that we sent for bomb calorimetry, so we had patients eat the meal, wait, aspirate, and then we took that gastric aspirate and sent it for bomb calorimetry, and we sent the identical meal for bomb calorimetry, and we did it in four different test parameters, a 450 calorie meal either at 20 minutes or 60 minutes after the meal with aspiration, and an 800 calorie meal waiting for either 20 minutes or 60 minutes for aspiration, and what you can see is that we got about, for the 450 calorie meal, about twice as much, it's twice as many calories out for if patients aspirated right at 20 minutes versus the 60 minutes, but for the 800 calorie meal, it really didn't matter. There was almost 30% of calories that were removed regardless, and in terms of the total aspiration time, it took somewhere in between seven and a half and ten minutes in order to actually do the aspiration. In terms of weight loss, we have a number of studies that have actually been done. We have the pathway study, which is the randomized multi-center controlled trial in the United States, the US pilot study, a Swedish pilot study, a super obesity study with patients with a BMI of greater than 55, a European registry, and a Swedish comparative study, and we can see that all of the weight loss is really pretty similar out at year one with 14, about 14 and a half percent versus 21 and a half percent total body weight loss, and out at year two, we see again that we're in that 15 to 25 percent total body weight loss range. We also did a meta-analysis for the ASGE and looked at aspiration therapy, and we included four studies at one year with 373 patients in the intention to treat analysis and 296 in the per protocol analysis at year one. We have less patients at years two, three, and four as you can see here, but if patients continue aspirating, if they continue the therapy and in what was included in this trial, in these trials, is that we see at year one that we have about 16 and a half percent total body weight loss in those patients, or I'm sorry, about 17.8 percent total body weight loss in those patients who completed at least one year of therapy, and about 16 and a half percent in those that were in the modified intention to treat analysis, versus years two through four where we have somewhere between 18 and 19 percent total body weight loss as long as you continue doing the aspirating. There were 3.8 percent serious and non-serious adverse events as determined by ASGE grading system, but we had buried bumper in 2.2 percent, peritonitis in 0.5 percent, severe abdominal pain after placement of 0.5 percent, pre-pyloric ulcer in 0.3 percent, and there was a device malfunction requiring replacement of the device in 0.3 percent as well. In terms of the adverse events that occurred in the US pivotal trial, which I think is a little bit more representative of what we see in clinical practice, in the first year, most common was peristomal granulation tissue, and then second most common was pain, abdominal pain, less than four weeks after a tube placement, and then you can see the other adverse events which occurred at lower rates. In years two through four, the most common serious adverse events were peristomal granulation tissue again, and peristomal irritation, and we're going to talk about that in a minute. In year one, there was five serious adverse events in four subjects that all resolved, and then in years two through four, there were two serious adverse events, but also 12 gastrocutaneous fistulas that required additional therapy in order to close, and what we found at our center is that we can get these to close endoscopically, but it does sometimes take multiple procedures in order for that to happen. Also of note is that there was no evidence of worsening in eating patterns. Just to talk just one minute about granulation tissue, this is proud flesh, that's kind of what it's termed, due to trauma resulting in continued skin healing stage. You can reduce this, and this happens with PEG tubes, so this is a common thing we also see with feeding tubes as well. So we first want to stabilize the A-tube, keep the site clean and dry. I usually try to stop the proton pump inhibitor if a patient is taking that, if possible, because it just kind of helps to keep acid in the stomach and kind of keep that intragastric portion of the tube clean. We also use granulation, and that's something that you can purchase online, and that was developed to help kids, pediatric patients who had PEG tubes. If that doesn't work, then I go up to silver nitrate treatment. If that doesn't work, I'll change the tube out, and I'll ablate all of that granulation tissue with argon plasma coagulation, and then replace the PEG tube, or the A-tube, I'm sorry. In the pathway study, the randomized controlled trial in the U.S., the multi-center trial in the U.S., eating behaviors were assessed, and they were assessed with the eating behavior, the questionnaire on eating and weight patterns, as well as the eating disorder examination, which is actually an interview that determines whether or not it's actually able to diagnose eating disorders. We did this assessment at baseline week 14, week 28, and week 52. There was one control subject that developed binge eating at week 28 and was removed from the study, but there were no aspiration therapy subjects that showed any worsening of eating behaviors. In terms of frequency of aspiration monitored by connector counts, so you have to connect up to the skin port in order to open the skin port and aspirate, and that has a counter on it, so we know exactly how often patients are aspirating, and there was no evidence of any subjects excessively aspirating, and in clinical practice, it's really more of an issue to try to get patients to aspirate. In terms of self-reported eating behaviors, 91% of patients reported strongly agreeing or somewhat agreeing to increase chewing, like we talked about, you gotta chew a lot in order for food to actually pass through that A-tube, and 78% reported significantly or somewhat decrease in calorie consumption. In addition to that, patient acceptability was pretty high. I know this was not a survey that was necessarily validated, but we essentially just asked, overall, are you satisfied with your experience, and if it were available, how likely would you be to remember it, to recommend it to a close friend or relative? We saw that really most patients were satisfied, and most patients were somewhat likely to recommend this to a friend or family member. Last topic, transpyloric shuttle. This is not a space-occupying device like the balloons. It is a device that causes intermittent gastric outlet obstruction. It's placed during an endoscopic procedure, and first, an overtube is placed, as you see here in this animation. That is placed under direct visualization, but the device itself is actually assembled in the stomach, not under direct visualization. You'll see here that there's an outer sheath of silicone, and that outer sheath of silicone will be filled with a coiled cord of silicone. Here comes that silicone that will be coiled inside that smooth silicone sheath. It gets wound up into the larger part of the transpyloric shuttle, and then there's a cap that is placed on that to keep it in place. At the bottom end, there's actually a little weight that is tethered to the larger part of the transpyloric shuttle, and what that does is it helps to allow the transpyloric shuttle to bob in and out of that pylorus, and when it bobs close to the pylorus, it blocks empty of gastric content. This is what one of the TPS looks like in the stomach, and you can see the side here. You can see that there is that coiled cord of silicone that's inside that smooth sheath, and on the other picture, we see the locking mechanism in place, that cap end that holds that coiled cord of silicone in place. This was the first pilot study that was a previous generation of the transpyloric shuttle. There were 10 patients that went out to three months, and another 10 patients that went out to a total of 10 months, and we can see, and again, this was an open label pilot study. At three months, we had a little over 8% total body weight loss, and at six months, there's a little over 14% total body weight loss. They did have some non-serious adverse events, sore throat, some nausea, vomiting in these patients, and some feeling of heaviness and abdominal pain, but overall, it was fairly well tolerated. Now, this previous generation of device did not have the smooth outer silicone sheath, and it also had a cap end that was raised, and so that was associated with ulcers, and there were 10 patients that actually had ulcers, although most of those ulcers were asymptomatic. So that was changed, as we showed you, the actual device that was used in the End Obesity 2 trial in the U.S. for FDA approval was all smooth, and that cap end was flat, so it really took away the issues that were associated with the previous generation of the device. In this study, we had patients that were randomized to the TPS and in the control arm. This was a randomized sham controlled study, so again, these patients did not know that they had the device, and then there was an additional 32 patients that were in an open label portion at the end of the study, and that was just due to needing to have a few extra patients for a change to the device itself. We can see that there was a BMI was about 36 across the board, and then some of these patients had a diabetes hypertension or hyperlipidemia. Weight loss in the active arm was 9.5% at 12 months. Again, remember, this is a randomized sham controlled study, so we expect that, just because of this study design, we'll see less weight loss than we saw in the open label pilot study. In the control arm, we saw 2.8% total body weight loss at that 12-month mark, so a significant difference in weight loss between these two arms. In terms of non-serious and serious adverse events that occurred with this device, we see that there were a significant number of patients that had nausea, upper abdominal pain, vomiting, dyspepsia, abdominal distension. These are symptoms that we would expect for patients who are having intermittent gastric outlet obstruction, but most of these were rated mild or moderate and did not require additional therapies. The other thing that's important to note is that in this trial, patients were required to maintain a diary of their GI symptoms, and so we may have seen a little bit of over-reporting of symptoms compared to other trials that didn't have a diary reported, because patients, especially for symptoms that are mild, may not report those symptoms at an appointment a week or a month later, but would potentially write them down in a diary. There were some serious adverse events that occurred, but these occurred in only six patients. Some of these were overlapping events that actually occurred, and these all resolved. Unfortunately, the transpyloric shuttle currently is not commercially available, so we are still waiting for this device. Although it is approved by the FDA, we are still waiting for this device to actually be commercialized so that we can use it for patients in the United States. In conclusion, endoscopic bariatric therapies are evidence-based therapies with randomized controlled trial data supporting their use. In clinical practice, we see that weight loss is higher than what we see particularly in randomized sham-controlled studies, so that's really important to remember when we're actually talking to patients about the trial data compared to what we expect to see in clinical practice. We do see less weight loss than what we see in bariatric surgery, but significantly fewer complications and at a significantly lower cost. I'll take questions at our break. Thank you.

endoscopic bariatric therapies

intragastric balloons

aspiration therapy

trans-pyloric shuttle

Aspire Assist system

clinical considerations

weight loss outcomes

metabolic improvement