speaker will be Dr. Raman Muthuswamy. He's a mentor of mine and I'm honored to introduce him. He's a recognized leader in advanced endoscopic procedures. He's currently a professor of clinical medicine at the David Geffen School of Medicine at the University of California, Los Angeles. Dr. Muthuswamy is a member of the ASGE Quality Assurance and Endoscopy Committee. Good morning. I'd like to thank the ASGE and Dr. Day for the opportunity to be with you today. As was mentioned, I'm gonna talk with you today over the next 40 minutes about the landscape of infectious risk to patients undergoing endoscopy. Is it too much hype or just the beginning? These are my disclosures. So today I'm gonna really primarily focus on minimizing endoscope transmitted infections and really the focus will be primarily on duodenoscope transmitted infections because I think that's where the greatest challenge lies at present. I will briefly talk about infection control in the COVID era. Hopefully that era is waning here, but I think there are some lessons that we learned with regards to aerosol transmitted diseases and droplets related disease that may be something that we can carry forward in case future such pandemics or infectious agents develop. So I'll start with endoscope and associated infection transmission. We've traditionally said that this is a very rare event. The estimate was 1.8 per 1 million procedures and prior to the last decade or so, there was only about 281 cases of GI endoscopy related infections, which were mostly due to Salmonella and Pseudomonas. However, this is not only related to GI endoscopy. We can see this in bronchoscopy. There have been reports of mycobacterium tuberculosis, atypical mycobacteria as well, and there's even reports in the urology literature with regards to ureteroscopes. Viruses certainly can be transmitted with endoscopes. Hepatitis B and hepatitis C have both been reported as noted, but not HIV. And specifically, I would say that with regards to ERCP, this issue actually is not as recent as we may think. There've been reports of Pseudomonas outbreaks that go back to the 1980s and Klebsiella in the early 21st century. And we really started seeing them about CRE, particularly in 2014. And what's different about these issues are that until these recent outbreaks, we had typically all endoscopic related cross-contamination was usually associated with a major breach in the cleaning protocol that was identified, but we did not really see that with the duodenoscopes. And I'm gonna show you evidence in the next 10 minutes to support that. So as I mentioned, this has been going on for a while. There was a report in 1987 from Minnesota that found Pseudomonas aeruginosa in bile cultures from 10 patients who had an ERCP going back to 1984. And they did environmental cultures and a review of the instrument disinfection, and they traced all the infections back to one endoscope, a duodenoscope that was contaminated with Pseudomonas aeruginosa serotype 10. And although that device had been cleaned multiple times with an automated endoscope cleaning machine, the bacterium survived on residual moisture, which again is a critical issue, which I think Dr. Day will be discussing later, left in the channels of the device. And the contamination really only ended after they manually started suctioning alcohol through the endoscope before air drying. In five of these 10 patients, Pseudomonas caused actual clinical infections, including a case of gangrenous cholecystitis, or even abscess, and a death. There was no factors that clearly identified those who became symptomatic from asymptomatic patients, and that's something that you're gonna hear about shortly. For all the patients that we know about with clinical symptoms, there are probably an equal number, if not more, who have the transmission of the infection, but may not display clinical characteristics. In asymptomatic patients, Pseudomonas was even recovered from the gallbladder bile up to two months after ERCP, and these doctors advocated monitoring bile cultures as part of procedures. So what's new here is that with ERCP now is that the bugs we're transmitting, the bacteria, are often drug-resistant and particularly dangerous, but that also allows them to become more easily traceable and allows us to do investigations to determine common homology. So let's trace back to the history of CRE infections with duodenoscopes. It really started noticing it in the United States in about early 2010s. Pittsburgh reported an outbreak in 2011 and 12. With the folks at the CDC, Advocate Lutheran identified an outbreak which involved 38 infected patients, and then Virginia Mason, between 2012 and 2014, had 32 infected patients with 16 deaths. In early 2015, several hospitals helped identify outbreaks, including my own, and we also helped some colleagues at Cedars and in Wisconsin identify outbreaks as well. So Senator Patty Murray of the state of Washington commissioned a report on this, which came out about a year after we reported our events. It was 301 pages. And it really kind of outlined the history of this, and it showed really that this can occur with all different kinds of manufacturers. It actually started initially in Europe, and CRE is actually a bigger issue there. At least it was a bigger issue earlier on, and some of the new drugs that are being used to try to treat CRE infections are emanating from European countries, because that's where they've identified this was a growing issue first. But you can see there's a variety of hospitals in the United States. You can see my hospital at the bottom, and we were actually the 19th site temporarily to identify this. And so it's just that we were able to fairly definitively say that it was the scopes that led to a lot of media attention. And you can see even after our report, there have been several additional sites. And again, you can see just even on this small subpage that all three scope types are represented. So this is an article that we wrote in Lancet-GastroHEP in 2018, really sort of summarizing all of the issues with duodenoscope-related infections. And if you go back, again, this is very small, and I don't expect you to read it, but the earliest outbreaks really were, there were even a few between 2002 and 2009. So you can see there's around six here, some in France, some here in the United States. And again, the point is that you see a variety of different organisms. Many were not MDROs. These early ones, several were not. And again, it's really with different types of manufacturers of scopes and different types of manufacturers of reprocessing devices. So it's really more a category related to duodenoscopes, particularly the elevator, than any particular brand, although the cases likely represent the appropriate market share. And again, there were so many cases, there's actually page two of this table, which sort of carries on. And again, we stopped around the end of 2016, which is where this took it up to early 2017 that we stopped for tabulating this table. So in summary, again, these outbreaks began in the early 2010s, as I mentioned, first in Europe and then in the United States. And we now know that there's at least 45 sites with more than 350 patients that have been infected. And this is likely an under-report, and I'll get to that in a minute. And again, this is really seen with all the manufacturer types. I will say that this peaked in 2015 with 250 reports of patient infections, and it's declined by 62% to fewer than 100 reports per year in 2017 and 2018. And it's unclear what the cause of that is. In my next talk, I'll sort of go over the enhanced reprocessing options that we have and how effective they've been shown to be in the few studies that we have to date. But for whatever reason, whether it's through those mechanisms or whether it's just due to a renewed commitment to the reprocessing HLD cycle, the number of reports have declined by about 62% to fewer than 100 reports per year in 2017 and 2018. But there were still three deaths of US patients in 2018 related to infections associated with transmission via duodenoscopes. So the problem is not entirely resolved, as I'll show you. So again, this issue of under-reporting is important because what we're seeing is most likely the floor and hardly the ceiling. And this is Alex Callan of the CDC commenting back several years ago that when infections do come to light, the CDC does not have a mandatory system for reporting these outbreaks. And instead, they rely on hospitals and local health departments to report outbreaks on their own initiative. And obviously, there may be disincentives to do that, which I'll get to here. The most common is that there's just uncertainty regarding the etiology. You may not have the resources to definitively prove that it was actually the scopes and technology to prove the association. And you may not necessarily entirely want to go that far anyways. It gives you some level of plausible deniability where people can say, well, we're not sure what the source is, but it might've been the duodenoscopes that we instituted as policy anyways. And so I think there's a lot of institutions just based on phone calls I received over the last five years that kind of fall in this bucket. There are also some that may have uncertainties with regards to obligations. You really should report to the manufacturer, the FDA, your health department, and CDC, but that doesn't always occur, as Dr. Callan commented on. And then there are, of course, fears of negative consequences from either regulatory bodies, such as CMS or public or state health departments, or the press, which certainly newspapers are very keen to sort of report these sorts of stories, as we know from personal experience at my institution. So after reporting our report outbreak to our local department of public health, it got picked up by the Los Angeles Times, and then it immediately hit national and world news, so much so that our head of infection control, Zach Rubin at the time, was, had to have a call at a press conference, which you can see there. You don't see me, because I was safely tucked away on the second floor of the building there in the back, but eventually, you know, they wrote several stories about it, and obviously I was included in subsequent stories, as you see here, in a story, you know, sort of entitled, A Killer on the Loose, that was written about four months after we reported, about six months, excuse me, after we reported our outbreak. So this, you know, can certainly have impacts on institutions, and I'll come to that a little bit later. So detecting these outbreaks, as I mentioned, is not easy, and, you know, this is a graph of CRE infections at UCLA in the year 2014, and you can see we're a big university hospital, transplant center in a big urban area, and you can see that there's some baseline level of CRE that was present in the institution. We started really noticing an outbreak in the November to January timeline, and you can see there's different kinds of CRE, and the one that was associated with our devices is the one in gray. So you can see there was a blue type, there was a yellow type, there was an orange type, different types of CRE, but it's this OXA, you know, 232, that specifically was the one associated with this. So you can see there was one case in October, two in November, two in December, and three in January, and that represents the source patient, and then subsequently, you know, infected patients after that. And again, you know, it took a couple of months of dedicated work by our infection control team to identify this, and that was done in large part because we were actually doing some research on CRE in general, and so that helped facilitate this, and in fact, that's the resource that was used by some other hospitals, including our neighbor hospital, Cedars-Sinai, to identify their outbreak. So we had seven patients, but it was split among four endoscopists over a period of around four months. So, you know, it doesn't necessarily raise alarm bells, and based on the clinical presentation, you know, patients don't necessarily become symptomatic the day or two after an ERCP, so you may not necessarily immediately make the link, but essentially, as I mentioned, there was a source patient who underwent two ERCPs, one with the scope in red, one with the scope in yellow, and then you can see that that scope was used on the remaining patients at some point prior to the gold star there, which was their culture positive date. So you can see the red scope was used in quite a few patients, and then you can see the yellow scope was used in two patients prior to that. So you can see overall, there was seven additional patients here. So, you know, we have seven duodenoscopes at the time. They all cultured negative repeatedly, you know, using multiple protocols, including the CDCs, and interestingly, we've used this ATP testing as a level of contamination, but the ATP testing levels were under 200, which is considered, you know, the upper normal in all of our cases. One scope was a little bit higher than the rest, but they were all within what would be typically considered normal. As I alluded to, the clinical presentation of these patients is, you know, variable. Many patients are not sick initially, and some even go home and become ill afterwards. There's a difference in resistance patterns among patients with related infections due to transmission of plasmids. So if you're just trying to figure out homology just based on the fact that they have the same resistance patterns, that won't work. That's something I learned, which I didn't know, and so they can even acquire different resistance patterns, and we even saw in some patients different resistance patterns from organisms grown in different parts of the body because they even can get changes once a patient's infected. So again, pan-resistant species can develop, and we dealt with one of those. And death, really, when it occurs, occurs often very slowly over weeks to months as bacterial infection slowly progresses, and it's really kind of almost a natural history of bacterial disease. It's not always a rapid progression, and I've likened it to watching lava approach your house and being powerless to do anything about it, and that's the frustrating thing. Despite using all these different antibiotics, nothing really seemed to help. And oftentimes what we noticed was that they got infections of the pancreas, which then subsequently eroded into vessels, which caused hemorrhage, which were in many cases the cause of severe injury or death. So this issue, in addition to these outbreaks, the FDA then said, well, let's just see how often duodenoscopes are really harboring contaminated organisms. So they commissioned a study with the three major device manufacturers asking them to go to sites that use their devices that they felt were good sites and properly reprocess the devices and had them develop a process by which they would culture the scopes after reprocessing and submit the samples. The FDA thought initially that there would be a bacterial contamination rate of maybe 0.4 percent. That was the pretest estimate. It turned out that in this study, at the conclusion, that it turned out to be around five percent for the two largest duodenoscope manufacturers in the US. This was about 12 times what they expected, and this is specifically for high concern organisms, GI pathogens, not contaminants that you might find on the counter. You can see there was an additional rate of low concern organisms, but the five percent that I'm reporting is simply from the high concern organisms. Then they did a human factor study, which showed that there was a high number of cases where there was incorrect pre-cleaning of the devices prior to performing the manual cleaning. You can see it was about 75-80 percent, had one incorrect step or more. When it came to cleaning the elevator, seven out of eight of one of the models had some incorrect step done. In fact, they found very concerningly that over a quarter of the reprocessed samples when they were observed, had more than 50 percent of the tasks missed associated with cleaning the elevator. This is a significant concern. Again, while there haven't been systematic breaches in protocol, there are many steps that takes about 20 minutes to manual clean these devices. There's a lot of steps involved. Someone being able to hit all of the steps correctly is a bit of a challenge. As you can see, even missing a substantial number of the steps can occur, at least in this case, almost nearly a quarter of the cases. The Dutch also reported a nationwide report of 73 centers. In the Netherlands, care is often consolidated to select approved centers given the way their health system works. There's 73 centers that are allowed to do ERCP in the Netherlands or perform it. They were invited to sample at least two or do nanoscopes or more. They each, depending on the model type, they would sample between four and six sites of the scope. The channels, the biopsy valve, the elevator, the recess, etc. Then all the cultures were done centrally. They define contamination as greater than 20 colony form units within 20 ml of any organism. Or if you had any GI or oil tract organism, even if you just had one colony forming unit, that counted. They got 92 percent of the sites, 67 of the 73 to participate, and they had 155 duodenoscopes sampled of which there were 10 models from three different manufacturers. In total, they got 745 individual sites sampled. What they found was on a per duodenoscope level, there were 33 duodenoscopes that were contaminated, which is 22 percent of the total. 23 duodenoscopes, or 15 percent of the total, were found to have GI or oil organisms. When you take a look at any level of contamination, they found that 39 percent of all centers, which was 26 out of the total of 67 that participated, had at least one contaminated device. You can see that even if you say, well, I'm going to cut that down a little bit because I'm only interested in the GI or oil organisms, you're probably still looking at a quarter to a third. Again, this is showing that again, this is a significant issue of persistent bacterial contamination of these devices after reprocessing. Again, it's still topical. This is an article that actually was in the New York Times in 2018 about this same issue. Actually, I take it back to 2019 about the same issue. What have we learned? I'm now going to go over four sites that had an outbreak and identify some of the issues that were identified at those sites. This is a site in the Netherlands, Rotterdam, that had an outbreak between January and April of 2012. They had 30 patients who had this Pseudomonas aeruginosa type of CRE. Out of those 30 patients, they identified 22 who had undergone ERCP with one of two separate duodenoscopes that they had recently introduced in the year or so prior. One was actually introduced within the time period. They typically averaged some baseline level of this type of organism at their hospital similar to as I showed you for CR8 hours. They found that there was a clonal relatedness confirmed between the patients and the organism that was identified in the elevator recess. They actually did a very impressive complete deconstruction of a duodenoscope including electron microscopy. Here's an example of what they did. They actually have the duodenoscope there. On the top left, you see the end of the duodenoscope. They found some identified cracks and damage. They then took the elevator down. They sampled the areas, the elevator wire channel port as you can see here, which had previously been sealed. Then it was sealed by this O-ring, which then they did electron microscopy on, and found that the O-ring in the sealed part actually had bacteria. Essentially, an area that was not supposed to ever be exposed to contaminant then became contaminated. Then of course, that was a potential mechanism for transmission to other patients. They felt that the fixed distal cap was felt to hamper cleaning of the elevator and disinfection. They found that O-ring may not seal this forceps elevator access sufficiently. Because of some of these concerns on this new model, the two duodenoscopes were removed from service. Here's a timeline of what happened at their place. You can see in green, and again, this starts in 2011. But to remind you again, this is more in the first quarter of 2012, that they experienced their clinical outbreak. Basically, they have some baseline level of this organism in the facility as you can see here. It's usually a number less than five. Then the red line indicates the use of this other duodenoscope and the number of cases that were associated of this infection, that were associated with someone getting an ERCP. You can see in the beginning, pretty rare, pretty rare, probably averaging between 0 and 1. Here, 0, 0, 0. Then suddenly, you see that the spike in the number of patients with this infection seems to correlate with almost nearly all of them having an ERCP and so they began a contact investigation. They identified the fact that this may be a device related, and then they pulled the scopes from use. Then you can see that the number of bacterial infections with this organism returned to the baseline and you can then see that really, they once again were almost hardly ever associated with ERCP use. Again, this is just another graph highlighting this issue. The light gray indicates the nodal number of ERCP procedures, and the darker gray is the number of procedures performed of that total using one of those two devices. You can see there was quite a bit of use of those devices during the time period where this outbreak occurred, which is in this first quarter of 2012. Then you can see the devices were removed from service, and I've gone over the arrows in terms of the infections on the previous graph. When they sampled the environment, they found that it was actually present in a lot of different places. They found it in sinks in patient rooms, in utility rooms, on the clinical wards. They found it in actually extra sampling in the forceps elevator recess and also in dismantling the cap of the endoscope. But anti-grade sampling of the duodenoscopes, they sometimes didn't find it and they didn't find it in the rinse water of the AER machines as well. That's a little bit about this experience in Rotterdam. Now we'll transition to Chicago to October 2014. This was a single center in the Chicago suburbs, 39 patient cases with 35 that had duodenoscope exposure. This occurred in the year 2013. This was a E. coli that was recovered from a duodenoscope, and it had a 92 percent homology to that recovered from patients. They found that odds ratio of having this organism to a duodenoscope exposure was 78, so really high. Essentially, they had on the top here in this small graph, these were the actual patients who had clinical symptoms, which then triggered this identification of the duodenoscope. Then they went and contacted the other patients who had had a procedure with that duodenoscope during that time period, and they found many more cases of people who were not clinically infected but harbored the organism. This shows you this tip of the iceberg phenomenon. The people on the top are the ones who actually had clinical infections, but the people on the bottom are actually the total number of people who had a infection period. You can see that it's actually equal to or in many cases more with that. Again, this is a slide that just shows the homology of the organism showing that it's essentially on gel electrophoresis showing that essentially these organisms are related and showing essentially a common source. The CDC field investigation findings were that the AER was appropriate for the device, that the equipment was maintained in service appropriately, and they did not find breaches in the reprocessing protocol for HLD in each of the individual steps shown there. They looked also at procedural risk factors to figure out cases versus controls who might be more likely to get transmission. I did notice that they had a significant risk that was associated with both biliary stent placement with an odds ratio of 2.8, but also brushing just below it at 2.0. They instituted an ethylene oxide sterilization protocol with subsequent culturing. This occurred and they did a study looking at this from October 13 to April 14, and they did sterilization with ethylene oxide after every use. They did monthly cultures. They increased the reprocessing time by 16 hours, which necessitated an increase in the number of scopes from four to six, in large part because they had, it looks like, easy access to it perhaps on site. They had four scopes that they noticed sustained damage during that time period, although it was unclear if it was from the ethylene oxide. But of note, there was one CRE positive culture that occurred after 18 months, even after sterilization. This was a different strain from the original outbreak. When they repeated the culture after another ETO cycle, it was negative. All the exposed patients were screened were negative for CRE. This is the time period they looked at. They did 589 ERCPs with 592 gas sterilization cycles. They did 84 cultures. They found four scopes with some damage, and again, the one positive culture rate, which was one for 84, 1.2 percent. They only tested for CRE, so it wasn't a culture for everything. They noticed the cost of the extra scopes, plus some other equipment was around 93,000 for this time period. I would argue many institutions have to buy substantially more, as you'll hear. This is the Virginia Mason experience. Again, 32 patients, 16 died by March of 2015. They typically harbored one or two strains of E. coli. Everyone had undergone ERCP or duodenoscopy. E. coli was found in four out of eight duodenoscopes, three of which required critical repair. Again, important to pay attention to perhaps unperceived device abnormalities. Although the scopes were functioning fine, again, no breach and reprocessing protocol infection control identified. Again, this was identified in part due to volunteer submission of bloody fluid samples to a state reference lab that was studying CRE beginning in 2012, and then they were notified of a novel cluster of this multidrug-resistant E. coli. This highlights where they found the organism. They found the organism of interest here in four out of their eight scopes, and they also found some damages in several of their devices that hadn't been noted as well. Again, this is a paper that discussed their outbreak. When they looked at characteristics of patients who were alive versus dead, since it was essentially equal between the groups, they really couldn't find anything that separated them, although they may have been underpowered. They then instituted a culture and quarantine protocol, which has really been adopted by many institutions around the world. They found that about two percent of their scopes that underwent HLD still had positive cultures. But once they instituted this protocol, they didn't report any further infections or outbreaks after that. The result of instituting this culture and quarantine protocol, which involved storing the scopes for 48 hours after reprocessing, required them to purchase 20 new duodenoscopes in January 2014. Cultures were taken after a single HLD using a CDC protocol. They then repeated the AER cycle after the culture, and then stored them vertically in a closet with passive airflow for 48 hours. If the culture was negative, they were released for use, and if they weren't, they were reprocessed, recultured, and quarantined again until they were culture negative. This little icon here shows their document on how to do this. Again, as I mentioned, they found 1.9 percent rate of bacteria in their culturing. Then over time, and I'll talk about this in my next talk, they were able to reduce this to around 0.7 percent, in large part due to eliminating one device, which seemed to repeatedly culture positive, and also probably perhaps to the use of a special brush to clean the elevator that was introduced as well. They got that down to 0.7 percent. Our study, looking at our outbreak, again, looked at risk factors with regards to transmission. We looked at all the patients who were either exposed to one of the two scopes in comparison of the patients who were infected to those who didn't get infected. We also collected their prior medical history and the techniques used during the RCP. We had 125 procedures that were performed on 115 patients with one of our two implicated scopes, 10 patients at two ERCPs. Ninety percent, we had data on their final culture colonization data, and unfortunately, 89 did not have any infection, but 15 had identified CRE transmission. Of note, we found eight with active infection, But then in this process of doing these cultures, we found seven more that were colonized but not infected. Again, showing that there may be an equal number that don't exhibit symptoms. So again, this is just a graphical representation of what I just told you in the timeline from October 14 to February 15. And what we found was that on univariate analysis, biliary stent placement, which again, similar to the Chicago experience, cholangiocarcinoma, inpatient status, and prior antibiotic use within 90 days were associated with this. And when we had, with transmission of the organism, and when we corrected for cholangiocarcinoma, active inpatient status and biliary stent placement was associated with colonization or infection with ERCP. And again, I think that makes sense if you, you know, drag something through a channel or elevator that may have bacteria and then allow it to get contaminated and then allow it to inoculate for many months. That may be a reason why we see stent placement. Again, when we looked at those who were colonized versus infected, stent placement and male gender appear to be more associated with active infection. So we don't see this very often because you need five steps to acquire an infection. And really, you have to have a patient who's infected with CRE, which fortunately is still relatively rare. Then that person has to undergo an ERCP, which is only about five to 700,000 per year in the U.S. Then you have to become colonized with CRE despite disinfection of the device. And that may occur, depending on the study, between 0.7 and 5%. I use 1.9 from the original Ross data. And then we found that about four, even if you had a contaminated device and underwent the procedure, only four, about one in seven would actually get transmission of the bacteria. And half of those may be colonized. And so only about half would actually get clinical infection from that. So I will say the impact on us. It's not hype if it happens to you. You know, we had to stop all duodenoscope for use for eight days. A lot of outpatient ERPs were canceled. We contacted the public health department. We had an on-site visit. We developed a plan going forward. ETO wasn't done because our cultures were negative. So we didn't feel... ETO was selected because our cultures were negative. And so we didn't think we could trust cultures since we couldn't culture them on our own organism. Plus our lab refused to do them anyways, because they don't do environmental samples. We had planned to do monitoring after high-level disinfection prior to ETO with culturing. But again, that was tabled for the same reason. We also added linear echoendoscopes to our new method. So basically we did the standard HLD, but then hung it overnight to dry. And then we sent it out for ethylene oxide sterilization. The scope returned initially the following day, but now because it's only allowed to be run once a week due to environmental issues, which I'll get to in my next talk, that we really have to wait up to 10 days depending on what day we use it. So it's at least a week and often more. The cost used to be 560 for a tote of potentially four scopes, but now it's 3,000 per tote, which is once a week. There's a courier fee to take it to the 40 miles away that we have to send them to get this done. The tote can hold four duodenoscopes, three linear echoendoscopes, or some combination of the two. And as I say, they pick it up around a little afternoon. When it does go into the sterilizer, it goes in at 6, and then it's out between 7 to 10 a.m. the next day, because you have to vent the cycle for some time. And then usually we get it back now, typically on Monday at 12 30, because it's once a week. So sterilization channels have to be dry, otherwise you'll develop antifreeze. That's why we have the overnight dry. There's obviously increased turnaround time, obviously substantial for us. Availability, it's not always available. It's usually not on site, and some states even have banned it altogether. There's a question of whether you need to, you know, you have to wait to avoid the residue, because that can be carcinogenic and can make people sick. And again, it has an effect on the scopes, makes them stiffer, but not necessarily increasing repair costs. And we did initially observe some scope leaks, but we didn't really see an overall increase. But if you don't take the cap off, you'll damage the scope. Most people make this mistake once. So regarding culturing, many sites have had their duodenoscopes repeatedly culture negative. You can't culture what you can't swab or sample. So there's issues with regards to that. We had problems on who would run the cultures. Our hospital lab wouldn't, and private companies were far away and charged several hundred dollars a scope. And some told us it would take them two weeks to get us back the results, which is impractical. The impact on our practice, we went from seven down to five scopes initially. We started using therapeutic linear echo endoscopes for ERCP for a short time till we could get more. And, you know, we did, if an ERCP scope wasn't available, we even used an EGD scope in some cases to clean out metal stents. And we transitioned to using radial US scopes as the initial scope for almost all US, unless we knew there was an FNA involved. We had to get many new scopes, and we ultimately ended up purchasing seven new ERCP scopes and 11 linear US scopes with processors. That cost about a million four. And then since then we've added another 10 to 12 ERCP scopes now, so that we have around 25. Institutional impacts include, and many of these occurred for us, drops in overall hospital inpatient census, a cancellation of surgeries and non-GI procedures, just due to fear of, you know, infection in general. We noticed a multi-year prolonged depression and screening colonoscopy volume due to safety concerns regarding endoscopy, and people were choosing FIT and Cologuard and other tests. We, to this day, continue to use our radial US device as the initial scope in all cases where we don't know FNA is certain. And we had to buy, as I mentioned, numerous additional elevator containing scopes. And some units in my state, because of CMS surveyors, are now actually behind the red lines, similar to ORs, because of concerns about this. Fortunately, we are not one of them. So I'll close briefly by talking about infection control in the COVID era. I'm not going to spend a lot of time on this related to contact and aerosol droplets. This comes from the ESG guidance on endoscope and practice operations and the AGA recommendations as well on this. And again, we're hopefully coming out of this pandemic, but in the future, you know, we may run into other sort of respiratory organisms and we may need to do this again, hopefully not. But, you know, we generally triage procedures as those that were urgent, emergent within two weeks, semi-urgent two to eight weeks, or elective, which were more than eight weeks, which included most screening and routine surveillance exams or chronic symptoms. Obviously, one general good practice is general distancing. One could argue we could do this even during flu season, checking alone or with one guest, with families waiting, maybe offsite or outside, spacing out the waiting areas, using physical barriers when feasible. And I think one benefit from what we've learned is perhaps we can use telehealth options for doing certain aspects of the check-in to facilitate and expedite the process. Screening patients for symptoms in advance was recommended as well. And then many places instituted testing for the organism within two to three days prior to the procedure. And again, patients with low sensitivity tests at many institutions were treated as empirically positive. On the day of check-in, again, a rapid questionnaire and temperature check, followed by immediate, you know, rooming of the patients in their bay, and then when possible, using the same bay for the patient to minimize cleaning, although that would require holding the bay open while they're in the procedure room, which would hurt efficiency. And of course, wearing masks for patients whenever possible. For the staff, again, all members should wear PPE appropriately, and GI procedures, upper and lower, should be considered aerosol generating. I will tell you there's some recent data I've seen suggesting that colonoscopy is an aerosol generating procedure. There was one study that suggested that through the Bobsy channel, but now there's some new data suggesting that it may not be more than just the Bobsy channel. Patients with known or suspected infection, COVID in this case, should be done in a negative pressure room when available. And perhaps one thing with these airborne infections is that we would try to make future endoscopy units, since they are aerosol generating, and we're, you know, may require intubation in some cases, which is also aerosol generating. We should have a greater number of our rooms, maybe even all rooms in the future, could be negative pressure if that becomes feasible. Administer nebulizers to reduce cough, extra procedure time for clearance of aerosol droplets in between cases, especially in rooms that don't have negative pressure, and where appropriate PPE. I think we've all gotten used to wearing masks, and we have different kinds of masks, including this PAPR device, and perhaps coming up with effective, comfortable, and low-cost masks that will handle these sorts of aerosols and small particles will be an area of future development as well for us. And I think we've learned the importance of eye covering in these situations as well, given the mucous membranes. We've gotten guidance on the proper order to don and doff our gowns. I won't go into that, but I think that's an important order to minimize sort of contamination and aerosol generation from the surface. And then we've learned about the best practices with regards to cleaning surfaces. The good news, at least for COVID, was that really standard disinfectants work quite well in eradicating it. It was just a matter of cleaning high-touch areas frequently. I think over time we've also learned that it's really more aerosol-based rather than surface-based as well. So in summary, prior estimates of infection risks related to ERCP were likely significant underestimates. Multigenerative-resistant organisms do allow for easier but still difficult tracing of infections, which can aid in identifying device-transmitted cases. Device transmission has probably been occurring for longer than we think, and clinical infection rates likely related to both procedure and patient factors, some of which I talked about. The clinical impact of an outbreak can be substantial from regulatory, legal, and or reputation-based perspectives. And preventing these episodes from ever happening should be our primary goal, primarily, obviously, for the benefit for our patients, but certainly for our practices and institutions as well. And finally, we should adopt best practices learned from the COVID pandemic moving forward, perhaps minimizing more contact, and this may be helpful during flu season, or if any future respiratory aerosol-type organisms become an issue. And I think that there are some best practices for unit design, flow, and operations that we can hopefully integrate long-term. With that, I'll stop, and I thank you for your attention. Thank you, Dr. Muthusamy, for that wonderful overview, and I think really starting off the course today. It was a great and comprehensive review of sort of all the current literature and challenges that we're seeing out there around infection control. One question I had is, based on your experience at UCLA, I'm curious how you and your practitioners there may have changed discussions with patients, given some of the infectious outbreaks that have been happening worldwide and even locally. How have these sort of been embedded in your informed consent process or discussions you may have with patients in clinic? Yeah, thanks, Luke and Dean, and good morning to everyone, and again, thank you to you and the SGE for the opportunity to be with you today. You know, the discussions, certainly it is something when I talk, you know, we always typically before an ERCP procedure have talked about the risk of infection. That's usually, you know, with typically endogenous infection, where we translocate the patient's own GI bacteria into the bloodstream, perhaps during injection. Now I sort of, you know, have modified that discussion to include infection either from the procedure or the device, and then I, you know, I don't necessarily spend a tremendous amount of time on that, but I do comment that there is a potential from that device, and if that leads to further questions, we answer that. Some institutions have formalized that and actually put that in the consent where they talk about that. We haven't formally modified the consent process, but I think our ERCP physicians have, you know, routinely as a group our practices to discuss all risks, including device-transmitted infection. And to follow up, I guess, on that, Luke, is, you know, initially we did get a lot of questions from patients about who are undergoing ERCP about that, and also for other procedures, and that's the thing is that it's important to control messaging and educate patients on where the risks have been identified and where they primarily lie and where there aren't, and as I mentioned in my talk, many people became concerned about colonoscopes and doing colonoscopy, and so we had to provide some level of reassurance over, you know, a fairly long period of time that these infections, you know, really were arising primarily from the elevator-containing scopes, particularly duodenoscopes, so I think those are important discussions to have with individual patients, but also with your population group at large to help them identify exactly where the primary issues were identified. Thank you, Raman. My second question is, is you had mentioned, I think, at the beginning, and we'll hear a little bit more about this, I think, in our next talk, but you had mentioned that your staff early on had some challenges around the cleaning of the duodenoscope, really around the elevator mechanism, and that was, you know, it's a really complicated process with multiple steps. I'm curious if you at UCLA or if you've heard from others how they have addressed this problem after it was detected and how you, you know, what best practices have you sort of learned from this? Yeah, I mean, I don't think that there were, in fact, we've had several, by protocol, there were no protocol breaches, so we didn't have any specific issues with regards to that, but I will say that the process itself is complicated, and so while you may not have any systematic issue where, you know, people are being taught incorrectly, when you have a complicated task that requires many, many steps that typically, even when done perfectly, last 20 minutes, one can certainly postulate that a certain percentage of the time, one or more of these steps is not performed correctly, and, you know, you have really the expert on that here with Corey Hofstad, and I'm sure she'll talk about that. Most of the work in this area really is based off her work, and so certainly you can imagine if there are 47 steps and each, you know, 97 percent of the time they're done correctly, you can see how, you know, that can lead to, you know, a significant number of times where maybe all the steps aren't done, and as we'll talk about, I think, later in the course, the margin for error with high-level disinfection, particularly with a high level of bioburden, is not that high, so it really does require that the steps that are there be done correctly, and so if you start getting some degradation of that, it doesn't necessarily take much, so it's really important, and I think we'll be talking about this over the course of the day, to really have proper training, validation, ongoing competency assessment, and one of the things I'm sure that you'll talk about and others is we need to make the process simpler for our staff, and because there's so many different types of scopes, models, it's very complicated, because you might have three different types of duodenal scopes, and each have slightly different manufacturer IFUs, and you have to remember, oh, with this one, I have to do that, and in units that may not do a ton of ERCPs, you know, you know, they have to, you may have a group of people who are doing it, they may not do this very often, so there's certainly lots of opportunities for improvement, you know, I can say that we have, you know, intermittently done some board scope studies, we have used increased frequency of competency assessment and created a set of training videos and so forth for our staff, so those are some of the steps that we've taken to help with that. I'm sure that, you know, other institutions have done, you know, similar and perhaps, you know, additional things as well.

Dr. Raman Muthuswamy

endoscopy

duodenoscope-transmitted infections

infection risks

outbreaks of CRE infections

detecting outbreaks

impact on institutions

infection control practices

educating patients