Dr. Jeanine Maguire: Thank you for joining us for today's very exciting webinar, brought to you by HealHorizon, sponsored by O&M Halyard, and in partnership with PAWSIC. Today's presentation is Healing Beyond the Surface: The Role of Skin Health and Patient Engagement in Advanced Wound Recovery, brought to you by Dr. Jonathan Johnson and in sponsorship with PAWSIC. And so, who is PAWSIC? PAWSIC is the Post-Acute Wound and Skin Integrity Council. PAWSIC is an interprofessional team leveraging individual expertise to collectively synthesize and integrate evidence-based practices from research, along with nationally recognized guidelines from collaborating organizations for wound and skin care. We advocate for setting the highest standards of care in the post-acute care practice area. And we acknowledge the complex regulations and reimbursement structures that challenge and impact the patient across their journey through the continuum of care. Finally, PAWSIC is a 501(c)(6) nonprofit. We are all volunteers. Please check us out@PAWSIC.org. And please join us today.

Today, the moderator is myself; I'm Jeanine Maguire. I'm the chief clinical delivery officer for Tissue Health Plus and the current president for PAWSIC.org, and I'm here with our wonderful speaker, Dr. Jonathan Johnson, chief medical officer for Tissue Health Plus, serving also as the founder and surgical director of Comprehensive Wound Care Services. Known as “Dr. Wounds,” he's also dual board-certified by the ABWM and the American Academy of Aesthetic Medicine. A few other things that I should note, he also has a fellowship at the Sylvester J. Carter Hand and Plastic Surgery at the Lincoln Medical and Mental Health Hospital of Cornell, and he has an MBA in Healthcare Finance from the Carey Business School at Johns Hopkins University. Neither of us have any disclosure, so this one's pretty easy. We are so happy to have you here today, Dr. Johnson.

Dr. Jonathan Johnson: Jeanine, thank you so much. Thank you to the PAWSIC team. Thank you to everyone who is tuning in today. And just a quick note, my mom wrote that resume, so that was not me. You have to blame it on mom. But listen, we want to have a great lecture today, a great interactive presentation. Today, we're going to talk a lot about wounds, some of the functions, and thought processes on the correct clinical management of wounds. We're going to look at everything from treating wounds to how wounds regenerate, and actually, also interacting with your patients to make sure they are on board with all your clinical decisions. So, some of the learning objectives, we're going to explore current research on skin regeneration. We're going to look at the impact of innovative treatments in skin barrier function, which is very important, and discuss some of the advantages and some of the techniques for supporting skin health throughout the phases of wound healing, which we're all very well versed in. And explore some of the strategies for educating our patients on their role in the recovery process.

So, that being said, we understand skin health and wound healing. But one thing we may not really realize is that chronic wounds have mortality rates that are comparable to cancers. So, if we look at a lot of the adverse issues with wounds from Charcot’s foot to diabetic foot ulcers to some of the bad outcomes or the adverse outcomes of wounds, major leg amputations, et cetera, they are comparable to some of the major issues with cancers that we see, lung cancer, all other types of major cancers. So, the key with this slide is understanding that treating wounds effectively initially is key so that the wounds, number one, progress in a normal stage of healing. But we also don't get to the adverse effects of wounds having issues with not healing because the adverse effects, again, amputations, et cetera, are comparable to issues with cancer. 

So, skin provides an essential barrier for health. And one thing we always like to focus on when we're looking at education, et cetera, is that the skin is the largest organ in your body. So, understanding how to effectively treat it on a day-to-day basis—but also how to treat it when you do have wounds—is effective in helping the skin heal, which also helps the wounds heal. So, skin provides a critical protective barrier to prevent infection and fluid loss. We understand that there is an acute wound healing format and a chronic, or what we call, nonwound healing format. Our goal is to help the body progress through the four stages of wound healing without delay and/or interruption. So, acute wounds generally heal, like we're saying, through the normal skin healing process. Chronic wounds are slower, and they result in the skin not being able to progress through the four stages of wound healing.

So, literally, any type of board question, wound care examination, will have the four stages of wound healing. So, you really want to understand this concept because, number one, you're going to be tested on it. But, number two, it's the formation and the foundation of what we do from a clinical standpoint. So, if we're thinking about the four stages, hemostasis is number one, we're looking at vascular constriction and the formation of our fibrin clot. Now, the fibrin clot is important because it is formed by platelets. It releases growth factors, cytokines, hormones, et cetera. So, think about when you have an injury to your skin, the scab or the plug is the first thing you see, and that's platelets rushing to the site of injury. So, that fibrin clot is that dark color and that change in the area of the skin once the initial injury happens. 

We move on to inflammation. So, we're looking at neutrophils. They're recruited to the wounds, and they help to digest some of that necrotic tissue, that adverse tissue, et cetera. And then, your microphage comes in and starts to remodel the extracellular matrix, and they transition to beginning angiogenesis. So, the extracellular matrix essentially is the wound bed starting to heal. We need that foundation in order to make sure the wound continues to progress and heal well. So, chronic wounds are stalled in this inflammatory phase. So, removing biofilm and reducing the amount of non-viable tissue overload will help the wound progress through the four stages of wound healing, which we'll discuss as we move forward. 

So, proliferation, epithelial proliferation is key. We're looking at migration, how that begins to occur, further strengthening the extracellular matrix, collagen formation, and capillary growth. So, all three of these components are important. And then, we get to our remodeling side where we're looking at the reformation of our vascular system and the reorganization of the extracellular matrix. I always like to spend a little time on this slide because it's important to see, number one, the visual effect. But you also want to make sure that whatever you're doing, you’ve got to focus on treating the wound effectively in the inflammatory phase if it's a chronic wound, so it progresses through the four stages of wound healing effectively. 

Alright, so when we are looking at our wounds that are chronic and stalled in the inflammatory phase, there are key factors that help skin heal effectively besides just the provider initially treating the wound at the wound site. So, we're looking at blood supply. We're looking at nutrition. We're looking at infection control and risk, moisture management, oxygenation, and lifestyle accommodations. So, it's really a multipractice or multimodal approach to support wound healing. 

Now, what does that mean? That means we're looking at bringing in a multidisciplinary approach as well. It's not just the wound care provider. It's the dietitian. It's the physical therapy team. It's the folks who focus on social work. It's even the patient's family, power of attorney, et cetera, and the resources they may need to heal psychologically as well. So, it's a large approach, and there are multiple factors that we need to treat from a clinical standpoint to make sure the wound heals effectively. 

So, one of the major factors that we have to understand when we look at a wound is looking at the moisture balance. Moisture balance is key. If a wound is too dry, we need to add a component or an initial treatment regimen to increase moisture. If there's too much moisture, we need to utilize a clinical resource to decrease the amount of moisture. So, the most important thing we want to look at is minimizing water loss. So, provide hydration. Increase the skin turgor. Balance and promote tissue regeneration.

The more moisture we have, the better for the wound to continue to improve. We want to maintain proper nutrition. As we said before, dieticians and nutrition are key because we need to promote protein building blocks. And a lot of times, this is the conversation you want to have with your patients. Hey, listen, you have to eat. You have to increase the amount of protein that you have in your body in order to build the protein building blocks that we need, the amino acids, other minerals, fatty acids, et cetera. Because it helps to increase, number one, optimal inflammation and wound healing. And, of course, the two major components that we need for any wound to heal are blood flow and oxygen. Without blood flow and without oxygen, we're not able to receive components of angiogenesis to decrease infection and increase our wound healing organization and control. It's really key to focus on moisture balance, to focus on nutrition, and to focus on blood flow and oxygen to the wound site.

So, we said before that an increased amount of biofilm, non-viable tissue, et cetera, keeps the wound in a stalled inflammatory phase. Our role from a provider standpoint is to reduce infection and manage the biofilm development. So, we need to identify infections and biofilm development, as we've been saying. We need to decrease slough tissue. Increase the amount of treatment to make sure we're decreasing the amount of exudate. We want to increase granulation tissue, decrease the amount of odor. And the more that we focus on removing the biofilm, the more likely the wound will continue to heal effectively. So, proper cleaning of the wound and proper debridement. Now, there are many types of debridement, which at another topic and another time we can go into the specificities of that. But you want to really focus on sharp debridement. You want to really focus on removing the devitalized tissue. I think about it like when you wake up in the morning—and when I'm educating patients, families, teams, et cetera— think about brushing your teeth. You have to remove the biofilm, which is the same type of tissue that you typically see on a wound, once you remove the dressing. It's the same type of biofilm you see on your teeth. So, brush your teeth in the morning. It's the same thing when you're treating wounds. 

So, we talked a little bit about the formation of chronic wounds, what happens, and the stall in the inflammatory phase. We also understand how acute wounds progress effectively. Now, let's look at skin regeneration and wound healing technology, right? So, we've identified the chronic wound. Now, how are we going to treat it effectively so that it heals? So, regenerative medicine in skin healing has been around for a long time, right? We need to make sure we understand that, again, the wound needs to progress through the four stages of wound healing. But you can improve that progression utilizing a specific type of treatment, right? 

So, these treatments include cellular and acellular substitutes. And understanding these types of treatments is key because you need to read what the wound is telling you, so you know exactly what to utilize. So, bioengineering skin substitutes is obviously a very hot topic right now. From a provider standpoint and from the wound world in general in our field, understanding the efficacy and the importance of skin substitutes is key. So, these are laboratory-grown skin tissues that aim to mimic natural skin structure and function. So, they're promoting faster and more effective healing. And again, you have your cell-based, which are your cultured skin cells, such as two main cells that we're going to talk about a lot, your keratinocytes and your fibroblasts, to create a graft that then can be applied to the skin. From an acellular standpoint, it's made from materials like collagen or hyaluronic acid that provide a support structure for the body to grow new tissue. So, your cellular fibroblasts, keratinocytes, and your acellular components, which are your collagen and your hyaluronic acid. So, those two components are what we utilize when we're looking at skin substitutes. 

So, you have cellular skin substitutes as well. So, these substitutes, again, promote cells. They bring mediators. And they really mimic your extracellular matrix. Again, the key is to grow that extracellular matrix. So, when we're having conversations with patients, et cetera, we're making sure that they understand that that beefy granulation tissue is really what we need. We want to promote that healing, ie, your extracellular matrix, as much as possible. So, again, back to the fibroblasts and the keratinocytes, these are primary skin cell substitutes. So, again, the fibroblasts are responsible for the synthesis of the extracellular matrix components. Your collagen, your elastin, your laminin, your glycosaminoglycans, and your keratinocytes are going to provide that protective barrier function. So, again, those two cells are what we're going to continue to talk about as we move forward. 

Alright, so stem cells. Stem cells are an extremely hot topic, not only in wound care but also in aesthetics. Because, again, we're looking at treating the skin effectively, reducing issues with aging, and also reducing issues with wound formation. So, stem cells have been applied. And their ability to differentiate into different various tissue cells, which include keratinocytes and, fibroblasts, and endothelial cells, is the basis of why we're using cell tissue therapy. So, there are two types of stem cell therapies. We're looking at our mesenchymal stem cells, and we're looking at our pluripotent stem cells, right? So, the difference between the two is that your MSCs, or mesenchymal stem cells, are literally stem cells that are derived from your bone marrow, adipose tissue, amniotic fluid, and something that we call Wharton's jelly. And your umbilical cord blood, the foundation is what I like to call it. So, they help to modulate inflammation. They also help to enhance angiogenesis and granulation formation. They also have a great effect from an antimicrobial standpoint because you want to continue to promote fibroblasts. Now, in contrast, we're looking at pluripotent cells. And these types of cells are more of adult stem cells that have then been reprogrammed into more embryonic base-level cells. So, they help to generate into a variety of different types of cells. And depending on the cells, it promotes healing at various levels of the healing rate. So, you're looking at wound closure. You're looking at the increase in collagen synthesis and angiogenesis as well.

So, one of the awesome techniques that we're doing a lot of research on and looking at the formation of this specific service line in both wound care and aesthetics is PRP. Now, everyone's kind of heard of the word PRP. What does it mean? But platelet-rich plasma essentially is taking a patient's blood, spinning the blood down in a resource, like a tube, and you're separating the plasma. Once you separate that plasma, the plasma contains platelets. And, again, these platelets have derivatives. And they have resources that help the wound heal, number one, and also help to regenerate and decrease aging in the skin. So, again, the platelets are involved in growth factors. Remember, they're promoting proteins and cytokines. And the good thing about it is, it's fairly inexpensive, versatile, and safe. Now, the one thing I will say about PRP is that first, you have to obtain the blood. So, you have to have someone who's great at drawing blood because you can have all the PRP techniques and the thought process and the conversations with your patients. But if no one in your office is excellent at drawing blood, it's going to be a long day because you have to stick the patient multiple times, and no one wants that. 

So, another topic we're looking at from a cellular skin substitute standpoint—and again, we're talking about the new treatments in regenerative-based wound care and skin treatment—is 3D bioprinting of skin. Now, what exactly does that mean? We're looking at a process where you're fabricating skin cells— and they're made of living skin cells, molecules, and growth factors to increase healing rates, right? So, the advantages here are that it's automated and you can quickly make the skin cells. There's flexibility to introduce a variety of types of cells and molecules to promote healing. We're also looking at the fact that it's easy from a 3D printing standpoint, lab-based standpoint, to produce and mass scale to help the wound progress and heal, and to make sure that you can reach multiple patients. So, the 3D bioprinting for skin in the cellular skin subs world is a fast and excellent resource moving forward. 

So, we have acellular skin substitutes, and these are your biomaterials. So, we're looking at either natural or synthetic. And one of the most important concepts here is that there are multiple advantages, right? So, they can be used as a wound dressing. They effectively promote wound healing. And they have the ability to retain proteins, growth factors, and nutrients, which are obviously needed in wound healing. You're improving the wound's elasticity and hydration, and you're also looking at resources from an antimicrobial standpoint. Now, elasticity and hydration are key because the more hydration your skin can contain and retain, and the more elasticity, the less likely you are to have dry, aged, disadvantaged-looking skin. So, you want to make sure you increase elasticity and you increase hydration. 

So, as we continue to progress, we're looking at advanced techniques for supporting wound health. And as we look at this specific treatment regimen, we're focused on growth factor therapy. Now, we're all fairly familiar with our growth factors. Again, growth factors focus on helping the wound continue to heal. We're using it from a cellular standpoint to promote and enhance the extracellular matrix. So, some of the growth factor therapy is topical. It can be a solution, a cream, an ointment, or a gel, and it does show therapeutic effects. So, three types. You have your platelet-derived growth factor, your epidermal growth factor, and your transforming growth factor-beta. Now, the major difference between these types of growth factors, number one, is that we're looking at promoting cell tissue growth. We're looking at promoting angiogenesis. And we're looking at seeing increased rates of re-epithelialization.

Now, the platelet-derived growth factors promote angiogenesis, whereas the epidermal growth factors focus on the increase in tensile strength in the new skin. And if we're looking at our transforming growth factors-beta, we're also looking at some of that early-stage re-epithelialization. It also plays a primary role in increasing angiogenesis. Now, just a word of caution, some of the topical growth factors on the market do require a high dose or high usage and/or repeated administration over extended periods of time. So, just make sure you're having fluid conversations with your patients, managing expectations so they understand the process, and it can take some time. 

Now, another major factor we're looking at, or another treatment factor we're looking at, is cold atmospheric plasma. I don't know how many folks out there are huge fans of the cold plunge. I remember back in the athletic days years ago—is that literally right after practice, the first thing we did was get into a cold tub to help decrease inflammation and help with the fluidity of blood flow to the muscles for recovery. Similar to the same process as far as a wound care treatment regimen, right? We're looking at the cold atmospheric plasma. And it contains a mixture of electrons, like reactive oxygen species, reactive nitrogen species. And, literally, a lot of these components help to reduce bacterial increase and growth. So, your reactive oxygen species and your reactive nitrogen species are antimicrobial. So, if we're removing the amount of bacteria from the wound area, we're increasing and promoting the extracellular matrix and remodeling. In addition, we're increasing the amount of angiogenesis. And we want to mediate the expression of those growth factors that we talked about before. So, a lot of these factors we can utilize in order to help the wound continue to progress through the four stages of wound healing. 

So, we're looking at the depths of the wound, the extracellular matrix of the wound, but let's also talk a little bit about supporting skin barrier function. We're all pretty familiar from a clinician and practicing standpoint that hydrogels are in an elastic and porous network. They increase the amount of water into a wound site. Again, if we're looking at moisture balance, if the wound has a decreased amount of moisture, you need to increase it with whatever treatment you're utilizing. Hydrogels are excellent for that. You also want to support the barrier function by absorbing too much exudate and providing a moisture-based balance solution and environment for the wound. So, some of the properties that support wound healing are non-adhesive, moisture retentive, absorb exudate, and allow for competent cell migration. The key to this slide is just remember that the wound is telling you what it needs. So, understanding moisture balance is key. 

We're also looking at technology in skin monitoring and assessment. I mean, if we're looking at some physical conditioning monitoring, that is key. We're focusing on biosensors, right? And biosensors continue to be a factor in health care in general, but specifically in wound care, because we're utilizing these in our patients, right? We're looking at temperature. We're looking at pressure. We're looking at pH. We're looking at multiple other factors—glucose, oxygen pressure, et cetera. So, some of these biosensors help to tell us the levels of these types of issues in the patient's overall body. So, it's helping us with resources we need from a wound care healing standpoint.

So, we've kind of talked a lot about the basics of wound care. We want to make sure the wound progresses through the four stages of healing effectively. We've talked about some of the advanced regeneration treatments that we use—stem cells. We're looking at skin substitutes. We're looking at utilizing growth factors. But you have to be able to put everything together to have a competent and clear conversation with your patient. Because without building that rapport, it's difficult to make sure that you're playing on the same team. And that's always key. Manage expectations, explain exactly what the treatment resources are, and what the proposed clinical management will be. 

So, with that being said, you want to establish personalized skin care approaches. So, that's tailoring treatments depending on the different types of wounds. You're looking at acute vs chronic, diabetic, surgical, traumatic, and atypical. There are multiple types. Bandaging and moisture management are key. We want to make sure that the patient still has a quality of life. And we want to make sure that whatever treatment you are implementing is accessible to the patient and easy to understand. And then, also addressing underlying conditions that do affect the skin in general. Remember, we're going back to that slide where there are multiple different factors that affect a wound's ability to heal. We're looking at diabetes. We're looking at high blood pressure. We're looking at venous stasis insufficiency. We're looking at obesity. You have to make sure that you're treating the entire patient effectively. 

So, again, educating your patients for long-term success. And that, again, goes with managing expectation and—managing expectations and engaging with the patient effectively and communicating with them. This is what our plan is going to be in order to help the wound heal. What's your thought process? Ask the patient questions so that they clearly understand what the plan is. So, again, engaging with patients in their wound recovery is literally key. So, patients who are engaged and interested, we've found from research, from just clinical experience, if they are involved in their wound healing, they're more likely to want to take care of the wound. They're more likely to want to change the dressings. But they're also more likely to reach out to a provider and/or a resource if something is going wrong, if there's an adverse effect, if there's increased bleeding, or if the smell of the wound doesn't seem like it smelled two or three days ago. Hey, the bandage hasn't been changed, but I need help changing the dressing. So, wound care requires effort, again, as we've been saying, and communication from the practitioner, the provider, and the entire system in general. So, the more onboard the patient is, studies show, the more likely the wound is to heal.

So, again, we want to build the community between health care providers and patients. And again, everyone on this great presentation and call understands that education is key. Being a great clinician means being able to educate effectively. So, you want to ensure patients understand the healing process. What is their role? Teach patients to identify some of the warning signs. This is what we were discussing just previously—infection, delayed healing. I think the number one issue is making sure your patient can actually look at the wound, right? And I'm sure the majority of folks that are on our presentation today have that one patient that says, “I don't want to see it, doc,” or “I don't want to see it. I don't want to see what the wound looks like.” But you have to continue to make the patient feel comfortable observing their wound so that they know if there are adverse effects. And you can teach them, hey, the wound is supposed to look beefy and red and viable. If you see it looking a darkish color, or it smells a different way, or you're seeing this type of exudate, please let us know. So, it's very important to make sure they understand that. Again, ongoing support and productive follow-ups. You want to continue to reinforce self-management practices and principles, and the importance of self-care and skin protection techniques is key as well. 

And again, I mean, this just goes back to building a holistic care plan. You know, we have multidisciplinarian—or multidisciplinary care teams that focus on patient-centered care, right? And again, this is what we discussed before—your dieticians, all your providers, your nurses, whom we can't really do anything without our nursing team. So, we always love them. Our physical therapists and our medical technicians. But also don't forget, sometimes it's psychiatry, right? Sometimes it's psychology. Sometimes it's involving the patients’ family members who may be active in their care and are really effective in helping them understand what's going on and helping them heal.

So, as we wind down to the end of the presentation, I know I've given you a lot of information about, again, regeneration, stem cells, looking at PRP, and looking at skin substitutes. And how the really progressive regeneration techniques we're utilizing in wound care are important and a useful resource for all providers, and just for our field in general. So, some of the key takeaways that we want to make sure everyone understands and gets from a deliverable standpoint are that chronic wound management requires specialized care, as we said before, and a multidisciplinary approach and collaboration. So, technology for treating chronic wounds continues to evolve. The number one thing in health care in general, regardless of the field, is to continue to read. There are multiple periodicals out there. I mean, PAWSIC is amazing as a resource. In order to make sure you're staying up to date, you're clinically competent, and you can find resources you need to be the best clinician you can be, the best provider, and the best management. And whatever field you're in, you want to make sure you're doing that to your best because ultimately it's positively impacting our patients. We want to continue to engage and educate our patients for optimal outcomes. So, again, the more that we do that, and the more that we focus on the primary goal, which is our patients, the better we'll be. So, I'd like to say thank you to everyone who's on this presentation today. I want to say thank you to the PAWSIC team, to the President, Jeanine Maguire, and to everyone who was involved in putting this together. Because the more education that we can make available for everyone in the field, the more it benefits our patients. So, I'd like to say thank you again.

Dr. Jeanine Maguire: Thank you for joining today's presentation. We will now begin the Q&A session. Our first question is, what about promoting angiogenesis or is that the role of negative and hyperbaric therapy?

Dr. Jonathan Johnson: Great question. So, first of all, I'd like to thank everyone that had a chance to listen to this excellent presentation today. Thank you for connecting. It's always great to continue wound care education. So, angiogenesis is key, in general, from a wound care standpoint. As we know, continuing to increase proliferation of the wound bed via granulation tissue via increase in the wound-based healthiness is always key. As far as HBO is concerned, remember, we're increasing the amount of oxygen pressure to help the wound heal effectively. Two most important concepts you need in healing of wounds—blood flow and oxygen. Great question.

Dr. Jeanine Maguire: Next question is, how do you go about initiating growth factor therapy serums, and when do you start?

Dr. Jonathan Johnson: Growth factor serums are definitely key, although slightly not used on a regular basis as the standard of care in wound care. But we remember that we increase our growth factors, and the growth factors are kind of like the batteries in our cells to help the wound proliferate and heal quicker. So, however you're introducing those cells, whether it's via IV, whether it's topically to the wound site, it's important to make sure that those cells continue to proliferate to help the wound heal effectively. Great question as well.

Dr. Jeanine Maguire: Next statement we have is, I am a home care and post-acute care nursing assistant. We are usually the most prominent care point in direct, hands-on care. Any thoughts there regarding that position?

Dr. Jonathan Johnson: Well, as far as direct and home care, it's key. You're the first line of defense. We appreciate everything that you do. Remember to just assess the wound, assess the patient, but also look around at your surroundings. There's many other socioeconomical issues or just issues within the environment that the patient is in that can help you increase the healing rate of the wound. Does the patient have a pet? Does the patient have a caregiver that's there for them? Are there obstacles in the way? Are there issues with device-associated pressure injuries? Does the patient fall asleep in the chair? Does the patient not have the best resources for turning and repositioning? So, it's always great to have these providers as first line and sometimes the only line of treatment. The key here is just to, number one, look at the wound. Number two, evaluate the patient's overall comorbidities and their overall health, but then also focus on the environment. All three of these concepts can help the wound heal quicker. Great question.

Dr. Jeanine Maguire: Next question is, are there recommendations for ways we can learn more about how to support wound care outside of wound care nurse visits?

Dr. Jonathan Johnson: So, there are many resources. There's periodicals. I mean, the WoundCon. HMP does an excellent job of making sure that there are periodicals and resources out there to continue to read. Besides just studying and looking at your journals and your online blogs and some of your online information, share your experiences with your colleagues. Join groups, join wound care groups, join some of our boards. The APWCA is a very strong board. And really communicate with your colleagues because their experiences can also help you out with your experiences. So, the more that we continue to share war stories and stories in general, and the great stories and sometimes the bad stories, it's key.

Dr. Jeanine Maguire: Thank you, Dr. Johnson. And thank you everyone for joining. This now concludes our Q&A session.

Dr. Jonathan Johnson: Thanks, guys. Take care.