With an eye toward the future, Dr. Manu Aggarwal and Dr. Mark Melin look thoughtfully at the wound care landscape, current treatment strategies, and the role vascular management plays in healing.

MARK MELIN is a surgeon, wound care specialist, thought leader, and educator. He is the Medical Director of the Wound Healing Institute at M Health Fairview, University of Minnesota. Dr. Manu Aggarwal is a venous and lymphatic medicine specialist and wound care practitioner in private practice in Lima, Ohio, where she

educates her local medical community on the importance of lymphatic medicine and vascular-oriented approaches toward wound healing. Here, the two put their heads together in an enlightening exploration of the current and future state of wound care.

Dr. Manu Aggarwal: Thanks for discussing wound care with us today as it relates to vein centers. From my own account, I have seen many openings and closings of wound care centers in my area. Patients travel hours to academic centers for their wound care. It’s interest- ing to see what has happened with wound care centers in the last decade. What is going on with wound care centers serving patients?

Dr. Mark Melin: How does an institution value wound care? Is it on the radar screen? Is it in the black or is it in the red, who’s the leadership? Is it surgical-based? Is it medical-based? There has clearly been some consolidation with larger entities, and engagement even with universities where a private wound center becomes a subset of an academic university. Some of that is good because you’re bringing in these well-honed treatment algorithms. And then ideally, it improves outcomes, improves economics, and decreases recidivism. However, when we start to really break down some of those protocols, we need to also focus heavily on the lymphatic and venous components, which we know result in restorative, and regenerative qualities for tissues.

And most of these other pathways aren’t focusing on this. It’s a great opportunity within the American Vein & Lymphatic Society (AVLS) to really emphasize this point, especially given the current changing landscape of CMS and complex tissue products ( CTPs), which used to be called skin substitutes. The application of CTPs ideally would be aligned with the 2014 Journal of Vascular Surgery (JVS) guidelines, 2015 Wound Healing Society guidelines and the 2022 European vascular guidelines. Guidelines based upon graded peer-reviewed published manuscripts advise the performance of venous duplex ultrasound for venous insufficiency in clinically diagnosed VLUs. With the rising rates of diabetes, metabolic syndrome, hypertension, hyperlipidemia, which are all risk factors for peripheral arterial disease (PAD), ABI and TBI should also be routinely performed, especially in legs/feet with edema as palpation of pulse can be unreliable.

Dr. Manu Aggarwal: Thank you, great points. What do you propose would be the algorithm?

Dr. Mark Melin: Perform ABIs and TBIs and if you need correlating data, get an arterial duplex ultrasound. These are all studies that could certainly be done within an accredited vascular lab. More than 20 to 25% of the VLUs we’re seeing now have a mixed arterial component. Identifying PAD is critical to wound management. Clinical determination of a venous leg ulcer is difficult. The treatment algorithm for a VLU is a challenge if a venous insufficiency study has not been performed. Application of societal guidelines or pivotal studies such as EVRA or ESCHAR is under-appreciated in many wound care practices. From an AVLS standpoint, I think that’s where we in leadership can bring value locally, regionally, nationally, to align with societal guidelines on these points of ABI, TBI, and duplex ultrasound for venous insufficiency.

This also emphasizes holistic medicine. If you resolve lower extremity venous hypertension with ablation and foam schlerotherapy and improve lower extremity lymphatic dysfunction, you actually make an impact systemically. There was just a paper in JVS within the past four months that talked about chronic venous disease and how it increases cardiac and cerebral morbidity and mortality. We should seek to impact systemic health in our vein and wound care centers.

Dr. Manu Aggarwal: Those are great points.

One of the challenges that I’ve run into is actually co-ordinating with a wound care center. Being in a small town, we’ve seen closures at one hospital, and staffing issues at another hospital. Do you suggest vein specialists and somebody that’s really passionate about treating VLU and venous hypertension connect with wound care centers? Or are we saying we need to start doing more wound care within our venous practices?

Dr. Mark Melin: You raise a very interesting and important point. In a hybrid model, which you’ve already opened in your clinic in Lima, where you saw a lack of services, you became a recognized regional leader. You moved forward to increase services to the patients that you have, which is phenomenal. If you look at vein centers across the nation, what percent do you think are making an effort as you’ve made?

Dr. Manu Aggarwal: It’s few. It’s difficult.

Dr. Mark Melin: Right, exactly. It takes more time.

And are you going to stock all those wound care products? I think the hybrid model is an interesting thing to discuss. Is there economic futility in the changing landscape of 2022? Might there be a renewed opportunity to start creating these hybrid models?

Certainly, the other option is better alliances between vein centers and wound centers. There’s certainly synergy—if wound care centers identify more VLUs, the more there is for vein centers to do. And the more C4-C5-C6 disease that the vein centers see, the more patients they can send to wound centers.

I think there’s just a general lack of recognition of those components within wound centers that would be fueled forward by simply doing the ABIs, TBIs, and the duplex ultrasound venous insufficiency testing. Make it a standard checklist for the initial consult for almost every initial patient consult.

Dr. Manu Aggarwal: That’s a great point. I think this could be something that could be easily incorporated into an ICAVL-accredited facility. Aside from proper venous reflex studies, the other component we’re not seeing in wound care centers is the lymphatic portion. You wrote a great article published in Wound Source back in February 2020 of how lymphedema plays a role in venous leg ulcers and even just in general wound healing. I feel another complication in wound care centers is this constant battle of Unna boots versus short stretch bandages versus inelastic bandages. How do we incorporate lymphedema therapy into wound care centers or is that again, a separate entity that’s only done in physical therapy centers?

Dr. Mark Melin: The new era of wound care should include the incorporation of lymphatics into both vein centers, as well as wound centers. We just had this discussion yesterday on the podcast LymphCast. Students are not significantly trained in lymphedema evaluation and treatment in medical school, yet. Two of my sons and a daughter-in-law are in medical school right now. The first year, the second year, there is little clinical teaching—they’re still teaching the old Starling curve of 1896! They are not incorporating the fact that with the revised Starling curve and the recognition of the endothelial glycocalyx all that lymphatic fluid, all that fluid that comes out through the veins into the interstitium—80 to 90% of that fluid returns to the central venous system via the lymphatics. This fact alone emphasizes the critical nature of lymphatics. So, if we begin to understand that lymphatics are connected to not only removing interstitial fluid, but also directly maximizing microvascular perfusion, clinical application becomes paramount. That’s why we have such a hard time getting VLUs healed and remaining healed. And all diabetic foot ulcers are recognized to have lymphedema because of the shedding of the hyaluronic acid component of the endothelial glycocalyx and increased vascular permeability.

Lymphatic function is directly related to improved immune system function, hence contributing to a potential decrease in cellulitis rates. Many papers have shown that when you decrease cellulitis rates, you decrease hospitalization. So now we’re decreasing the cost of care, yet improving outcomes. The National Academies of Sciences, Engineering, and Medicine published a 2022 textbook titled Understanding the Role of the Immune System in Improving Tissue Regeneration. So now immune function is recognized to result in soft tissue reconstruction.

We should be leading through the lens of lymphatics, and if we get lymphatic functionality restored, many of these wounds will heal without anything other than just basic good solid wound care.

We also routinely add micronized purified flavonoid fraction (MPFF). Data and RCTS demonstrate that MPFFs improve venous tone, lymphatic tone and decreases inflammatory markers. Additional nutritional bionutrients include Vitamins D, C, B12, B6, folate, arginine.

We’re so blessed with phenomenal leadership in AVLS and ABVLM. I really do think we’re on the cusp of a re- newal and revival to accelerate care in collaborative efforts.

Dr. Manu Aggarwal: What are your feelings on wound care within vein centers?

Dr. Mark Melin: I come from a surgical background and you are from a very well-rounded family practice background. Do you think surgeons tend to be more aggressive, that they don’t see elevated patient BMIs and the C6 patient as barriers to care? There is something internally that we have to look at in ourselves as phlebologists and as treating physicians. A physician in a wound care practice who doesn’t feel comfortable treating venous insufficiency in a C4 to C6 patient with elevated BMI, is being set up for a treatment failure.

I think if a patient shows up in your clinic in Lima with C5 and C6 disease and their BMI is at 40, with your passion, experience, and background, the patient is going to be well cared for. My concern is that in another vein practice that doesn’t have the background and maybe doesn’t even have the passion for wound care, that same patient may not get the same outcome. So maybe in that particular practice, finding ways to collaborate with a wound center is the best and correct thing to do.

We have to figure out our own limitations. That is a significant part of the answer.

Dr. Manu Aggarwal: We even talk about superficial venous versus deep venous insufficiency and the capabilities within our own specialty, which physicians are able to take care of which patients, and what level of disease they’re not able to take care of. I think it re- ally does depend on, as you said, the house that you’re in and what your capabilities are.

We incorporated lymphedema into our practice with a certified lymphedema therapist and we have changed, I’m proud to say, what lymphedema is for our local community, to the point where the hospitals have also additionally hired new and more lymphedema therapists. We also meet regularly with all of the lymphedema therapists in our area that we refer out to. We bring case studies in and every therapist discusses different cases, different types of dressings, different types of compression, what they are using.

Once we started meeting with the therapists, we found that everybody was kind of doing lymphedema therapy very differently. Some were doing MLD, some were not. Some were just putting patients on pumps and leaving them there for about half an hour to an hour, and then taking them off and sending them on their way. If we can all come together and discuss how we’re taking care of our venous patients with wound care and with lymphedema, we can really make a difference for our patients.

Dr. Mark Melin: I am very interested in your “why”? How did you arrive at a place where you were interested in having wounds as a component of your practice?

Dr. Manu Aggarwal: Unfortunately we’ve seen more wounds since the pandemic started. Patients were afraid to go to the hospital where the wound care centers are, or they just didn’t bother going to get treated because they were afraid they were going to get COVID. But before that, in the last probably three to five years, we started seeing an increased number of wounds in our practice. A lot of times patients were coming to us as referrals or they were coming to us out of desperation because they’d been going to wound care for years or several months. Common stories of these patients are, “well, I have this varicose vein sitting right above my wound. Do you think that has anything to do with my ulcer? I mentioned it to the wound care providers and they don’t think anything of it.” And so I was frustrated because I was seeing these patients with recurrent or non-healing wounds that were clearly venous and I wondered why they hadn’t shown up in my office sooner.

We discuss the source after doing a venous duplex study. We figure out what the next steps are going to be. We do the procedure. Patients are healed within a few weeks to about a month with proper compression and comprehensive treatment. I thought to myself, I feel terrible for these patients that are getting missed and not getting treated in a timely manner.

I thought to myself, what if we could be that first touch for those patients so that we can do the venous duplex mapping and we can do the ABIs and the TBIs and make sure of what the source is and make sure that we’re taking care of the underlying issue. So that is where we’ve come from to evolve into having wound care in our practice.

Dr. Mark Melin: What you’re talking about is intellectual curiosity. I think sometimes we can lose that intellectual curiosity. I want to recognize Dr. Caroline Fife’s blog on this exact topic that I just read today. If you do not remain intellectually curious, if you aren’t paying attention, if you weren’t situationally aware, all of this would’ve been missed, none of this would be happening, and your practice would be stagnant and without joy driven by your passion to constantly improve patient care.

Maintaining that stimulus of internal desire to im- prove ourselves for the length of our practice is so critical. Unless we maintain that intellectual curiosity and also have self-reflection about where we’ve made mistakes, we’re going to fail. We have to be quick to admit our failures.

We also have to run the checklist almost every time we see these patients. I’d love to have a storyboard with every one of my patients. Part of it would show the healing trajectory. If it flattens out, what did I do wrong? What did I miss? And every time I look at that storyboard, it would say when their last ABI was done, and the last time a venous ultrasound was done. Because if we get 3-4 months along the path of wound care and they’re still not healing, am I missing a squamous cell basal cell cancer, pyoderma, or some atypical diagnosis?

The wound care patients are typically not healthy and clinical circumstances can change over months of continuous care. When looking at an ABI that is six months old, remember, it can change. Repeating ABIs, and repeating the venous duplex ultrasound, are critical parts of the diagnosis and situational awareness.

If you and I were going to create an algorithm, the first thing is to look at the patient. The second thing is to listen to the patient and examine the patient. The third thing is to scratch, sniff, smell, and biopsy the wound if you don’t have a good clinical reason why the wound is present. Make sure the duplex ultrasound for vein insufficiency is ordered at the consult and make sure it gets done. So, when that patient comes back, run the checklist again, and the third time the patient comes back, run the checklist again.

Dr. Manu Aggarwal: You are exactly right. I think that component of repeating the studies is so valuably important. I see that also in my own practice where we will get them healed and they reach that plateau and then they just kind of stop. And you’re like, what happened? We sometimes forget to repeat the study!

Dr. Mark Melin: There are a couple of things we’re all subjected to boundary-wise, living on the earth, right? We’re subjected to a 1G gravity environment that constantly impacts our tissues. Blood flow is always going to go to the lowest point in a vein that doesn’t have an adequate valve. And it’s the same thing in lymphatics. That hydrostatic component and impact from the pelvis to the feet are quite significant. Then the other thing that we haven't even broached upon is phenotypes and single nucleo- tide polymorphisms and epigenetics, and the new data on sodium impact upon endothelial glycocalyx function and glycosaminoglycans resulting in decreased eNO production.

Just within the past 10 years, there is a renewed recognition of sodium impacting glycosaminoglycans, which stiffens endothelial cells and decreases endothelial nitric oxide production. The loss of downstream endothelial nitric oxide production is a significant negative to healing. That is why high sodium diets result in hypertension. Dermal swelling associated with high salt diets is a significant negative to wound healing. I’ve begun to ask my patients, are you using the salt shaker? And do you have any idea how much salt you take? The average American takes in 3,400 milligrams of sodium a day when it should be 2000 to 2200. And if a patient is on amlodipine and has a lower extremity wound, this medication should be stopped as amlodipine often causes significant interstitial edema that impairs wound healing.

We could do a whole hour talk just on nutrition and micronutrients for our patients. I think a lot of our wound care patients have low-level scurvy from relative deficiencies in Vitamin C. If you’re buying groceries from the gas station, you are not buying a lot of fruits and vegetables. May God bless our patients that are economically disadvantaged where they don’t have the same access to healthy fruits and vegetables on a daily basis that you and I do. The ability to go and exercise and the ability to have a lower level of stress is not available to everybody. Our economically disadvantaged patients are exposed to the constant stress of “how am I going to pay my next bill?” In those conditions, your adrenals are constantly being squeezed, and it’s hard to heal in an environment that is continuous “fight or flight”.

Then there’s the psychological part—some reports say at least 30% of our patients entering a wound clinic have a clinical diagnosis of mental illness; schizophrenia, manic depressive, anxiety, et cetera; those conditions make it really hard to engage a patient to heal.

These are all huge, huge barriers to helping patients to heal. However, if “we” all do this together, we can make great strides in the next three to five years.

Part of this significant stride would be establishing Wound Care and Venous and Lymphatic medicine as sub-specialty Boards, with their own Board exams, and ACGME-accredited national fellowships. Boarded specialties and sub-specialties improve education, improve outcomes, improve collaboration, and is the right thing for patient-centric care. We must collaborate on these initiatives and parallel pathways, that interestingly, have great and synergistic overlap.

Dr. Manu Aggarwal: So, what is the ideal team?

Dr. Mark Melin: If I could create the dream team, I would select a social worker, a registered dietician, certified lymphedema therapists, venous and lymphatic specialist, interventional radiologist, internal medicine, family practice, physical medicine and rehabilitation (PMR), podiatry, plastic surgery, dermatology, vascular surgery, and a pharmacist that would go over the medication list. And volunteers as patient advocates who can hold a patient’s hand, escort in a wheelchair door to door, and be another set of eyes and ears.

Dr. Manu Aggarwal: I think that’s a perfect start to a team. With our great societal leaders, industry partners, and schools, I anticipate we will change and improve VLU patient diagnosis, treatment and outcomes substantially. V