I am Maria Adela Aguirre, a clinical physician. Since 2010, I have dedicated myself to patient care, teaching, research, and innovation regarding amyloidosis. I am part of an interdisciplinary team—the Amyloidosis Study Group—at the Hospital Italiano in Buenos Aires, Argentina. Today, I am here to share our story—my story—with amyloidosis, and I hope you find it useful. Why did we establish an amyloidosis group in 2010? We were a group of healthcare professionals who wanted to improve care for these patients. We faced significant barriers when evaluating them: we struggled to make accurate diagnoses, patients lacked access to treatments, and we were unable to type the various forms of amyloid within our region. Knowledge was scarce, and patients suffered greatly—often passing away—while feeling isolated and lost. We identified colleagues facing the same challenges; we came together and agreed that we had to help these patients and drive progress in their care—advancements that would benefit not only our country in South America but the entire region. We knew we had to organize this effort in the best possible way. That is why we contacted Dr. Melini and the group in Pavia to learn about their methods. Some of us visited their center, allowing us to observe and mirror practices from elsewhere and adopt their model. However, we also felt it was important to share our story. In the 21st century, scientific standards dictate that sharing such information means publishing it; yet, to publish, we needed to understand our own patient population better. That is how—alongside the group—we launched an institutional registry. Since I work within an institution, we began to track and understand the experiences of patients treated at this single private center in a South American city. We established an institutional amyloidosis registry, obtained ethics committee approval, and reviewed cases from prior years—making our registry ambispective, with a prospective component that grew over time. We included data starting from 2006, noting that our group was formed alongside the registry in 2010. Following the advice of Professor Melini in Pavia, we decided to include all types of amyloidosis rather than focusing on just one, and to ensure coverage across all departments of the HI—the *Hospital Italiano*, our institution. We used a standardized data capture system; rather than individual practitioners simply entering their own patients, we employed a system validated by the ethics committee. The data were then validated by Lourdes—the registry director—and myself (a registry member) to ensure high quality. This allowed us to standardize processes and achieve the best possible data quality, placing special emphasis on quality and anonymization—safeguarding the data so we could adhere to research best practices. Concurrently, a multidisciplinary team was formed, enabling a comprehensive, real-time approach to patient care. This team operates through a specialized clinic established in 2014; while various professionals have joined over time, the core initiative originated with two remarkable women shown on the slide: Dr. Patricia Sorroche and Dr. Elsa Nucifora. They were essentially the founders of this group and brought us together back then—when we were all younger. Here we are—along with Dr. Soledad Sáez and myself—at an International Society of Amyloidosis meeting in Kumamoto, Japan, where two biochemists, a clinician, and a hematologist gathered to share and acquire knowledge and experience to bring back to our country. A group gradually took shape, comprising hematologists, neurologists, nephrologists, biochemists, and experts in pathology, gastroenterology, various types of organ transplantation, ophthalmology, and cardiology; the final additions were dentists and a team of dysautonomia experts. This allowed us to collaborate on diagnostic, therapeutic, and follow-up decisions for these patients based on a solid consensus, ensuring the patient felt evaluated and supported by a team—an entity that transcends the specific individuals involved, as we are always there, and our decisions are invariably reached by consensus. As this small group evolved, the GEA (Hospital Italiano Amyloidosis Study Group) was established in 2010; you will see that we started out as a very small number of people. Professor Malini encouraged us to develop these concepts and care practices among professionals in the region and to disseminate them, suggesting we hold a symposium with numerous international guests. Professor Malini visited Argentina three times to support us, and we were able to hold our first symposium, bringing together colleagues from various specialties; we continued to grow through successive symposia. In 2014, we held another symposium attended by Professor Rapezzi, and we were able to identify key findings regarding pyrophosphate scintigraphy—even before the validation study was published by Professor Gilmore from the UK—as we were already familiar with scintigraphy data and had begun using it to diagnose transthyretin amyloidosis.

At our third symposium, we were able to carry out activities related to clinical care and begin sharing details about our practice. By then, we had several years of experience under our belts; we could discuss specific cases, patients, challenges, and diagnostic errors, and we had gathered a sufficiently interesting dataset to draw some conclusions. We also focused heavily on educating our colleagues. We adopted a systematic approach that involved giving talks at hospitals and health centers and consulting with fellow physicians; if a case of amyloidosis was identified somewhere, we would hold a clinical case conference afterward. We also began developing our own lines of research—such as the validation of light-chain assays and sequencing methods, and studies tracking how many patients admitted to the Coronary Care Unit for heart failure were subsequently diagnosed with amyloidosis. To this day, we continue to evaluate other aspects of care, such as healthcare costs, patient empathy maps, and the patient perspective through our patient registry. We have moved from the 2023 symposium—when we launched our institutional amyloidosis registry—to the present, where we have expanded into a multicenter registry. This achievement was made possible by our ongoing collaboration with scientific societies and colleagues across various specialties; by sharing data and allowing professionals from across the country and the region to contribute their own findings, we have been able to generate much more valuable and robust data. You will notice many more photos on the right side of the screen, reflecting the growing number of people joining our team. Furthermore, there has been a steady increase in both publications on amyloidosis and the number of patients enrolled in the registry. This represents organic progress across all areas of the group; for us, it is crucial that all our pillars grow in a sustained, organic, and balanced manner. So, who are our patients? Who comes to our center? Well, initially, we mostly saw patients living near the hospital—specifically in the Almagro neighborhood of Buenos Aires. However, over time—thanks to word-of-mouth and our efforts to spread the word among colleagues—patients began arriving from all over Argentina, and eventually from across Latin America. The pandemic and the associated lockdowns also popularized teleconsultations; consequently, we started conducting remote consultations for patients in other countries. We now consult with patients from various nations—including in Europe—who are seeking a second opinion, wish to communicate in Spanish, have family in Argentina, or are Argentine expatriates wanting to stay connected. As for health coverage, we accept all types: from patients with the hospital’s own prepaid plan to those referred by other private health schemes, as well as patients who come for private, self-funded care.

So, how do patients arrive? What is the starting point? How do they find this group? Well, some patients are referred; they look at networks, speak with other patients or patient groups, and decide they want to be treated by this team—so they self-refer. Many colleagues also ask us to evaluate patients from across the country and the region; thus, referrals can come from another professional or from a patient who knows them. What brings patients here? Some come because they suspect they might have amyloidosis—perhaps they heard about it in a webinar or spoke to a patient with similar symptoms—and want to find out if they have the condition. Others have already been diagnosed with amyloidosis but haven’t had the specific type identified yet; we’ll discuss the technology involved in that shortly—specifically, the minimal technological strategies we use to aid in diagnosis. Some patients have been typed but haven’t started treatment; they want our validation or a second opinion to confirm if the initial treatment plan is correct. Then there are patients already undergoing treatment who ask us to handle their follow-up—or simply to consult with their doctors periodically—so we can stay in touch and provide ongoing second-opinion support. This process seems complex—and it is—but let’s talk a bit about it. How do they arrive? Here is the pathway: a patient with suspected or confirmed amyloidosis comes to the amyloidosis study group. Sometimes—I should mention—we face barriers to entry; for instance, patients might not be able to find us, or they call the hospital and the staff there doesn’t know who we are. Other times, they simply can’t locate the hospital; these are all barriers to access. If a patient has a diagnosis of amyloidosis, we confirm it by reviewing existing studies or ordering additional tests. If the patient does have amyloidosis, they are referred to our multidisciplinary clinic; if not, we connect them with other specialists to continue their care. If the clinical picture strongly suggests amyloidosis but we cannot definitively confirm it, we keep the patient under our care and maintain contact with them and their other physicians. We continue monitoring them because, given the diagnostic challenges associated with this disease, the condition might not yet be clearly diagnosed—perhaps the disease hasn’t fully manifested or there isn’t enough amyloid present to be detected. If the patient is confirmed to have amyloidosis and requires treatment, we encounter a second barrier: confirmation. Patients sometimes lack the means to access the technology needed to identify the specific type of amyloid. We don’t always have every type of confirmatory test available for everyone, which can be a hurdle. However, once the amyloidosis has been typed and we are ready to treat the patient, we conduct a risk assessment. Is the patient at high risk or low risk? “High risk” generally refers to the risk of organ failure, death, or a life-threatening crisis occurring in the near future, regardless of whether treatment is administered. If a patient is high-risk—for example, presenting with advanced heart failure, renal insufficiency, or severe dysautonomia—we assess whether they need immediate hospitalization to begin treatment or even require life support or organ replacement; in such cases, other specialist teams are brought in, such as those specializing in bone marrow, heart, or kidney transplantation, as well as oncology teams. For low-risk patients—who make up 95% of the total—we provide outpatient care, with the capacity for weekly or even more frequent visits; these patients continue to be monitored at the amyloidosis clinic. Regardless of whether a patient is high-risk or low-risk, once they are stabilized, we periodically evaluate their treatment and prognosis, provide ongoing follow-up, and determine if any adjustments to the therapeutic approach or monitoring plan are needed. To this end, we created an informational guide for patients—one of several outreach materials we share, including on social media—to ensure that patients facing barriers to care can quickly get in touch with us. We know—as anyone working in the field of amyloidosis is aware—that patients often present late; our primary goal is to ensure patients can connect with their doctors and access the appropriate treatments in a timely manner and with the greatest possible precision. What methods do we have to differentiate and type the amyloidosis once the patient has been diagnosed? How do we determine the type? Because doing so opens the door to initiating treatment. We have several tools available—many developed by our own group—such as high-precision serum free light chain assays (kappa/lambda ratio); validated *in situ* transthyretin gene sequencing (a method validated in Pavia); and tissue immunohistochemistry for transthyretin, AA amyloid, and kappa and lambda light chains. We also utilize pyrophosphate scintigraphy—interpreted by specially trained team members—and PET scanning with wall assessment using optimal imaging and reporting techniques. We perform strain imaging daily, working closely with our cardiac imaging specialists for consultation and follow-up. We use cardiac MRI with T1 mapping to measure extracellular volume, allowing us to monitor treatment over one or two years to track amyloid progression or regression. We collaborate with dentists to perform salivary gland biopsies—obtaining ample tissue—which became possible thanks to a highly motivated dental team; consequently, we avoid abdominal fat biopsies unless strictly necessary, opting instead for salivary gland biopsies. Finally, we are working with the University of Buenos Aires through a research consortium to implement mass spectrometry; this technique has already been validated at our center, marking a major milestone for the entire region. But all these developments were made possible because of the team we nurture so carefully; the human element fosters the technological. We have highly valuable people, and we want them to work as a team and develop their careers in the best possible way. Many of these developments go hand-in-hand with master’s and doctoral theses; we want everyone to find their place and achieve satisfying personal and professional growth. Talent retention is crucial to us, as is the ability to offer our patients the best technology backed by the best available evidence in this part of the world. What are they? How did we do it? After all, we didn’t just wake up one day to find all these tests already in place. In 2009, we gained the ability to perform in-house free light chain testing. In 2010, as I mentioned, the institutional registry was established. Subsequently, we validated transthyretin sequencing. In 2014, we introduced immunohistochemistry for amyloid A. In 2015—prior to the publication of the Gilmore study—we made pyrophosphate scintigraphy available. In 2016, we began to familiarize ourselves with and understand strain imaging for both AL and TTR amyloidosis, and later that year, we gained access to T1 mapping. We also implemented salivary gland biopsies; however, it took much longer—with a pandemic intervening—before we could recently secure typing via mass spectrometry, currently the best available technique for patients who could not be diagnosed through immunohistochemistry.

As I mentioned at the start, these were my roles—or rather, the pillars of the group: clinical care, teaching, research, and innovation—and this is what we focus on. We operate through collaborative networks. We work with scientific societies and attend symposia. Our junior members rotate and work with other groups because we believe in interconnection, in the value of groups, and in collaboration. We also build networks with scientific societies—starting locally and nationally, and extending to international organizations—to improve the approach to amyloidosis. We are deeply committed to improving access within the region, so we collaborate with American and European groups, regional scientific societies, organizations across various specialties, and amyloidosis groups worldwide; we view this not as competition, but as a mutual exchange where we all learn from and collaborate with one another. This mutual cooperation ultimately benefits the patients. We invest a great deal of time, money, and personal effort, but we derive immense satisfaction from cooperating—whether it involves referring a patient to another center when necessary or having a patient from the region come to our center—because, in the end, it is the patients who benefit in terms of both quality and length of life. We also work closely with the patient community—which, as I mentioned, is at the heart of what we do—engaging both with established patient groups and with individual patients who reach out to us spontaneously. We have participated in, celebrated, supported, and shared in Amyloidosis Day activities in various ways—ranging from in-person events to webinars—as well as Rare Disease Day. We maintain a patient registry that documents the experiences of patients and their families living with amyloidosis, and we are currently developing an empathy map; we value understanding the patient experience and learning how to improve our practice to enhance the quality of life for patients, their families, and their caregivers. We also maintain relationships with the industry. For us, “industry” is not a dirty word; we believe in honest relationships and good research practices—prioritizing, as I mentioned earlier, the anonymization of patient data. While we may collaborate with the industry on publications, we maintain independence regarding the generation and dissemination of scientific content. We never share raw data with the industry; instead, we may benefit from joint projects, but we are the ones who publish the findings. We retain full autonomy over publishing results—no one alters our results, discussions, or opinions—and we independently develop educational projects. Although these are often funded by the industry, we have complete freedom regarding the design, speakers, and agenda. This freedom offers us immense possibilities, allowing us to make clinical decisions independently, regardless of our industry collaborations. Another project that was crucial for the region—and one that makes us increasingly proud as time goes by—is the development of clinical guidelines. We began work on these guidelines in 2019 and completed them during the pandemic, adhering to best practices such as formulating PICO questions and using the GRADE methodology. We assembled a massive development team comprising methodologists and experts, collaborating remotely with specialists from both within the country and across the region. These guidelines bear a distinct regional stamp and remain highly relevant today; they are a source of great pride for us, and we have since been able to update them. How did we implement this care model, and how has it managed to endure for 16 years? We strive to maintain funding for the center, despite facing significant limitations; consequently, we aim for slow but steady growth. Retaining talent is a challenge—as I mentioned earlier—so we try to hold onto our young professionals by offering them a clear path for an academic, scientific, and clinical career. It hasn’t all been a bed of roses; we have little protected time for our activities, often sacrificing time with our families and our own rest. Even so, we derive great satisfaction from our work. We lack a dedicated physical space, so we meet wherever we can—sometimes using hospital rooms for brief periods or during limited time slots. Space is at a premium in hospitals, and we have no administrative support, so we take on administrative and secretarial roles ourselves to keep moving forward.

Those are the challenges we face right now, but if I may offer a recommendation: we shouldn’t dwell on the negatives. Everything can be improved; there will always be errors and things that could be done better. However, if we recognize that everything is open to improvement and growth, and we channel our energy into that, things will surely get better. We often start with few allies, yet we want to grow—to keep growing. But we’ve also learned the importance of starting small and winning those small battles first in order to build something great later on. We didn’t start big on day one; we began by looking at our own registry—first internally within the institution—before eventually expanding to the national level and across Latin America. It’s about moving forward step-by-step; we don’t build a house starting with the roof. We seek allies—partners in the region, friendly centers, and peer institutions. They aren’t competitors; they are colleagues. We can work with them, knowing there is a professional who can provide the best possible care to our patients when they no longer have coverage at our center or cannot afford a consultation fee. It gives us great peace of mind to know there are trained professionals with whom we can talk, discuss, and reach a consensus. We believe trust, empathy, and ongoing support are vital to sustaining the team for years to come, and we also understand that the team, the project, and the plan will endure even after we are gone. That is very important to us. We believe in sharing resources, knowledge, and opportunities. It makes no sense for several of us to carry out the same practice for a relatively rare disease—competing to see who does the most volume—when we could each specialize in a specific aspect and share those practices among ourselves. Well, that concludes the presentation. I hope you find it useful and that our experience—mine and that of my entire team—proves helpful to you. We are now available to answer any questions you may have. Thank you very much.