One of the organs most frequently impacted by amyloidosis is the kidney. Dr. Jeffrey Zonder from the Karmanos Cancer Institute provides a brief summary of amyloidosis and the most common types of this disease. From there, he goes on to describe how AL (Light Chain) and AA ((Apo)serum Amyloid A) are the two most prevalent types to affect the kidneys, detail how amyloidosis affects the kidneys, how this damage is assessed, and strategies for reducing kidney damage.
While both AL Amyloidosis and Multiple Myeloma are plasma cell disorders and share similar patient care treatments, they diverge in pathogenic mechanisms. In this presentation, Dr. Giada Bianchi from Brigham & Women’s Amyloidosis Program shares that 10-15% of Multiple Myeloma patients will experience overlapping AL Amyloidosis, elevating the importance of understanding the similarities and differences in diagnostic criteria and patient care.
Dr. Sarah Lee, Assistant Professor of Medicine at the University of Washington, provides a brief clinical overview of amyloidosis.
Amyloidosis can present in many types with the three most prevalent being light chain (AL) amyloidosis, hereditary variant transthyretin (ATTRv) amyloidosis, and wild type transthyretin (ATTRwt) amyloidosis. Being a rare disease, diagnosis can be particularly challenging, given that the general medical community is not well educated on the malady and symptoms are often associated with other more common ailments.
Successfully diagnosing the disease requires a two-step process before an appropriate treatment program can be determined and implemented for each patient.
- First, if amyloidosis is suspected, testing must be done to confirm the presence of amyloid.
- Second, once the presence of amyloid is confirmed, testing must then be done to identify and confirm the type of amyloidosis.
It is crucial that the second step, where the correct type of amyloidosis is identified, as the treatment regime can be different for each type. Here we share two different patient experiences which illustrate successful execution of the two-step diagnostic process.
Patient Case #1
The first case involved a 23-year old female. In 2017 she experienced an episode of coughing up blood, after which she looked in her throat with a flashlight and discovered a sizable lump. The patient met with a local ENT, who incorrectly diagnosed allergies, and prescribed over-the-counter medicine. With no improvement, she met with a second ENT. Testing was performed on the patient’s left oral pharynx utilizing a Congo red staining biopsy process which confirmed the presence of amyloid in the tissue. Additionally, mass spectrometry was performed which successfully differentiated the type of amyloidosis as being ALH (lambda light chain and delta heavy chain). Subsequently, she was referred to a hematologist who ordered a bone marrow biopsy and blood testing. The bone marrow biopsy summary notes read “….in conjunction with the concurrent finding of monoclonal lambda light chain restricted plasma cells in the marrow by flow cytometry, the findings are consistent with involvement of the marrow by a plasma cell neoplasm.”
Additionally, the blood testing confirmed elevated light chains as shown below.
Patient Case #2
The second case involved a man in his mid-fifties. He began experiencing disease symptoms approximately 6-7 years prior to being diagnosed in early 2019. He initially experienced gradually progressing numbness in his feet, legs, hands and forearms, as well as bilateral carpal tunnel syndrome. Soon after, he began experiencing symptoms of lightheadedness and fainting. Additionally, he started experiencing progressive gastro-intestinal issues such as acid reflux, chronic coughing, and frequent bouts of constipation and diarrhea. By 2018, his physical condition was rapidly deteriorating, including a total weight loss of approximately 80 pounds. During this extended period of time he was seen by a variety of physicians including internal medicine, neurology, endocrinology, gastroenterology, oncology, and cardiology, none of who were successful in arriving at a conclusive diagnosis. His list of maladies included cardiomyopathy, peripheral neuropathy, autonomic neuropathy, bilateral carpal tunnel syndrome, and gastroparesis, all which are classic symptoms of amyloidosis.
Finally, in early 2019 his condition was successfully diagnosed by an amyloidosis specialist. An echocardiogram was performed as well as a cardiac MRI (utilizing a gadolinium tracer) to identify amyloid fibrils and related damage in the heart tissue. These tests confirmed the presence of amyloid. A free light chain serum test was performed which ruled out AL amyloidosis, and Transthyretin DNA sequencing was performed to differentiate between the hereditary variant and wild-type of ATTR, which identified the T80A (legacy T60A) variant of transthyretin (ATTRv) amyloidosis. The two tests were successful in identifying the type of amyloidosis. The associated testing results are show below.
Echocardiogram Summary Notes
Associated Cardiac MRI Interpretation
DNA Sequencing Result
Once Diagnosed, Next is a Treatment Plan
Once the presence of amyloid is confirmed, and the type is identified, then it is time to treat the disease. In each of these patient cases the disease was diagnosed utilizing the two-step process to identify and confirm the type of amyloidosis. In both cases, successful treatment regimens were implemented which were effective in putting the disease into remission and/or halting disease progression.
Treatment options for amyloidosis have been vastly improved over the past several years. What was previously considered to be a foregone fatal disease can now be a manageable chronic disease. To ensure the best patient outcome, a timely diagnosis utilizing the two-step process, is essential.
Amyloidosis is a multi-system disease, making diagnosis challenging. In this informative patient guide, the American Society of Nuclear Cardiology (ASNC) discusses common symptoms, types of amyloidosis, red flags to be aware of, diagnostic tests and available treatment options.
CLICK HERE to read/download ASNC’s Guide for Understanding Amyloidosis
Multi-systemic diseases such as amyloidosis are complex to diagnose, but also complex in treatment and ongoing patient care. It takes a village. In this seminal piece, the American College of Cardiology (ACC) provides an Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis.
According to Dr. Vaishali Sanchorawala, Director of the Amyloidosis Center at Boston Medical Center, “The results and progress in the therapeutic landscape of systemic amyloidosis are unbelievable, unprecedented and unheard of for this uniformly fatal disease of the 1990s. But they are not enough, and therefore we need to work together to make a difference.”
This paper is an absolute must-read for cardiologists and other specialties such as neurology, gastroenterology, nephrology and hematology. To read, click on the image below.
Kittleson M, Ruberg F, et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis. J Am Coll Cardiol. 2023 Mar, 81 (11) 1076–1126.
Neuropathy, also known as peripheral neuropathy, is a broad term that is used to describe damage to the nerves outside of the brain and spinal cord. There are over 100 types of peripheral neuropathy that can be classified into four categories, with each type having their own symptoms and prognosis. In this article, we’ll discuss the types of peripheral neuropathy and its connection to amyloidosis.
One of the challenges with neuropathy is the fact that symptoms can vary significantly based on what nerve is damaged. Additionally, symptoms can develop over the course of months to years (chronic neuropathy) or come on suddenly (acute neuropathy). Some of the most commonly seen symptoms are listed below:
- Muscle weakness
- Muscle twitching
- Loss of muscle and bone
- Changes in skin, hair, or nails
- Loss of sensation or feeling in body parts
- Loss of balance or other functions as a side effect of the loss of feeling in the legs, arms, or other body parts
- Emotional disturbances
- Sleep disruptions
- Loss of pain or sensation that can put you at risk, such as not feeling an impending heart attack or limb pain
- Inability to sweat properly, leading to heat intolerance
- Loss of bladder control, leading to infection or incontinence
- Dizziness, lightheadedness, or fainting because of a loss of control over blood pressure
- Diarrhea, constipation, or incontinence related to nerve damage in the intestines or digestive tract
- Trouble eating or swallowing
- Life-threatening symptoms, such as difficulty breathing or irregular heartbeat
Types of Neuropathy
- Motor Neuropathy → Damage to the motor nerves control how you move.
- Sensory Neuropathy → Damage to sensory nerves control what you feel.
- Autonomic Nerve Neuropathy → Damage to autonomic nerves that control functions that are involuntary (ie. you do not consciously control).
- Combination Neuropathies → Damage to a mix of 2 or 3 of these other types of neuropathies. For example, damage to both sensory and motor nerves would result in sensory-motor neuropathy.
Peripheral Neuropathy is one of the hallmarks of amyloidosis, often seen in the transthyretin form of amyloidosis (ATTR). ATTR-PN, or transthyretin amyloid polyneuropathy, is a disease where the transthyretin protein becomes unstable and misfolds. This unstable protein (“amyloid”) then deposits in the nerve tissue, resulting in damage to these nerves. While amyloid deposits primarily in the peripheral nerves, it is not uncommon for amyloid deposition in the autonomic nerves as well.
While peripheral neuropathy is most commonly associated with ATTR amyloidosis, it should be noted that peripheral neuropathy is also seen in 15-35% of patients with AL amyloidosis.
Most importantly, these are the most common and important signs and symptoms to be aware of, in order to diagnose ATTR amyloidosis.
Looking to learn more about peripheral neuropathy in amyloidosis? Check out this wonderful video, where the Amyloidosis Support Group hosts Dr. Chafic Karam to discuss the topic in great depth. https://www.youtube.com/watch?v=9PsSST2gOIg
Cardiomyopathy is a broad term that is used to describe disease of the heart muscle, making it difficult for the heart to provide the body with an adequate blood supply. It can lead to heart failure and even death. In this article, we’ll discuss the types of cardiomyopathy and its connection to amyloidosis.
It has no ideal target, as it can affect a person of any age, race, or gender. However, there are a number of risk factors that can put one at an increased chance of developing cardiomyopathy.
- Genetic History → Family history of cardiomyopathy, heart failure, or sudden cardiac arrest
- High Blood Pressure → Over a long period of time
- Heart Conditions → Past history of heart attack, coronary artery disease, or infection of the heart
- Obesity → Tends to make the heart work harder to perform its normal function
- Alcohol Use → Long period of alcohol use
- Drug Use → Use of illicit drugs, such as cocaine, amphetamines, and anabolic steroids
- Medications → Drugs used in the treatment of cancer, such as chemotherapy and radiation
Additionally, there are a number of diseases that increase the risk of developing cardiomyopathy, including:
- Connective Tissue Disorders
- Hemochromatosis (excess iron storage)
- Thyroid Disease
Types of Cardiomyopathy
- Dilated Cardiomyopathy → Dilation of the left ventricle prevents the heart from pumping effectively. It most commonly occurs in middle-aged men and is typically the result of coronary artery disease, heart attack, or genetic defects.
- Hypertrophic Cardiomyopathy → Abnormal thickening of heart muscle, most commonly affecting the muscles surrounding the left ventricle. This type of cardiomyopathy is strongly associated with a family history of the disease. There have been genetic mutations linked specifically with this type of cardiomyopathy.
- Restrictive Cardiomyopathy → Stiffening of the heart muscle results in an inelasticity, making it difficult for the heart to expand and fill. It is most commonly seen in the elder population. The disease can be of idiopathic origin or of disease such as amyloidosis. This is the least common type of cardiomyopathy.
- Arrhythmogenic Right Ventricular Dysplasia → Scar tissue replaces healthy tissue of the right ventricle. This form of cardiomyopathy is rare and often the result of genetic mutations.
- Unclassified Cardiomyopathy → All other forms of cardiomyopathy fall within this category.
Cardiomyopathy is one of the hallmarks of amyloidosis, often seen in the transthyretin form of amyloidosis (ATTR). ATTR-CM, or transthyretin amyloid cardiomyopathy, is a disease where the transthyretin protein becomes unstable and misfolds. This unstable protein (“amyloid”) then deposits in the heart muscle, resulting in thickening and stiffening of the heart.
The two types of ATTR-CM are wild-type ATTR-CM (wtATTR) or hereditary ATTR-CM (hATTR). wtATTR-CM is the most common form of ATTR-CM, affecting predominantly white males 60+ years old. hATTR-CM is genetic affecting both men and women, and presents as early as 50+ years old. Interestingly, one of the mutations causing hATTR, V122I, is seen almost exclusively in individuals of African ancestry. It is believed that approximately 3-4% of African Americans carry this mutation, regardless of whether or not they develop symptoms.
Most importantly, these are the most common and important signs and symptoms to be aware of, in order to diagnose ATTR amyloidosis.
According to the Cleveland Clinic, “Proteinuria is due to increased levels of protein in the urine.” Your kidneys filter waste products from your blood while retaining what your body needs — including proteins. However, some diseases and conditions allow proteins to pass through the filters of your kidneys, causing protein in urine.
HOW DOES PROTEIN GET INTO URINE? (1)
Protein gets into the urine if the kidneys aren’t working properly. Normally, glomeruli, which are tiny loops of capillaries (blood vessels) in the kidneys, filter waste products and excess water from the blood.
Glomeruli pass these substances, but not larger proteins and blood cells, into the urine. If smaller proteins sneak through the glomeruli, tubules (long, thin, hollow tubes in the kidneys) recapture those proteins and keep them in the body.
However, if the glomeruli or tubules are damaged, if there is a problem with the reabsorption process of the proteins, or if there is an excessive protein load, the proteins will flow into the urine.
WHAT ARE THE SYMPTOMS OF PROTEINURIA? (2)
Often, someone with proteinuria doesn’t experience symptoms, especially if kidneys are just beginning to have problems. However, if proteinuria is advanced, symptoms can include:
- More frequent urination
- Shortness of breath
- Nausea and vomiting
- Swelling in the face, belly, feet or ankles
- Lack of appetite
- Muscle cramping at night
- Puffiness around the eyes, especially in the morning
- Foamy or bubbly urine
Conditions that can cause a temporary rise in the levels of protein in urine, but don’t necessarily indicate kidney damage, include:
However, according to the Mayo Clinic (2), there are diseases and conditions that can cause persistently elevated levels of protein in urine, which might indicate kidney disease, include:
- Amyloidosis (buildup of abnormal proteins in your organs)
- Certain drugs, such as nonsteroidal anti-inflammatory drugs
- Chronic kidney disease
- Endocarditis (an infection of the inner lining of the heart)
- Focal segmental glomerulosclerosis (FSGS)
- Glomerulonephritis (inflammation in the kidney cells that filter waste from the blood)
- Heart disease
- Heart failure
- High blood pressure (hypertension)
- Hodgkin’s lymphoma (Hodgkin’s disease)
- IgA nephropathy (Berger’s disease) (kidney inflammation resulting from a buildup of the antibody immunoglobulin A)
- Kidney infection (pyelonephritis)
- Multiple myeloma
- Nephrotic syndrome (damage to small filtering blood vessels in the kidneys)
- Orthostatic proteinuria (urine protein level rises when in an upright position)
- Rheumatoid arthritis (inflammatory joint disease)
- Sarcoidosis (collections of inflammatory cells in the body)
- Sickle cell anemia
HOW TO TEST FOR PROTEINURIA (3)
The only way to know if you have protein in your urine is to have a urine test. The test will measure the levels of protein in your urine.
The name of the urine test that measures the level of albumin in your urine is called the urine albumin-to-creatinine ratio (UACR). A UACR compares the level of albumin to the level of creatinine (a waste product in your blood that comes from your muscles). A normal UACR is less than 30mg/g.
Amyloid can harm the kidneys’ filtering system, causing protein to leak from your blood into your urine. The kidneys’ ability to remove waste products from your body is lowered, which may eventually lead to kidney failure and the need for dialysis.
When you have a patient with proteinuria, investigate why and don’t assume the obvious. There are many causes, one of which may be amyloidosis.
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Our mission is to educate future doctors about amyloidosis, with the belief that heightened awareness will lead to earlier diagnosis and ultimately improve patient survivorship. We know that the level of medical school education about amyloidosis runs the gamut, from a small mention in textbooks to classroom discussions with medical professionals, although the bias is overwhelmingly towards the “minor mention.” In addition, you’ll read below about our exciting expansion into residency programs – those new physicians now practicing and diagnosing patients. As a result, we are confident our efforts will provide a valuable enriched exposure to this disease to augment the medical school curriculum and residency didactic programs.
- Last year, we set our 2021 goal at 60 presentations, with hopes that the year would emerge from the 2020 pandemic onset. For the most part, it did. We gave 34 presentations in the Spring, and 27 presentations this Fall. Combined, these 61 presentations were to more than 2,400 medical students and physicians! Go us!
- Of the 61 presentations, 59 were virtual and 2 were in-person. Of note, both of the in-person were to our newly launched residency program outreach. Schools, with students returning to in-person in the Fall, remained largely closed to guests. Looking ahead we anticipate seeing a few more in-person, but virtual is likely here to remain in a big way for the foreseeable future.
- Our recent expansion into internal medicine residency programs (over 550 of them across the U.S.) has already resulted in 6 presentations on the calendar for 2021 and 2022. Our custom video specifically focused for this audience has been very well received and provides an excellent clinical educational complement to our patient stories.
- We average around 35-40 speakers, which allows for diversity in our speaker population’s disease state and flexibility in their availability. This has served us well. (more on that below)
- We are particularly delighted that our medical school student mailing list – those interested post-presentation in continuing to receive information about amyloidosis – continues to grow and is now around 350! Each month we email brief information about some aspect of amyloidosis, with the content pulled from experts and other trusted organizations. Our goal is to keep amyloidosis in their mind as they approach graduation and begin seeing patients.
- In October we held our first webinar, “Discover the Power of the Patient/Physician Collaboration” with guests Dr. Rodney Falk and hereditary ATTR patient Sean Riley. We ourselves were very pleased with the discussion and insights, although the attendance fell short of expectations for medical student turnout.
- With the help of one of our speakers Dr. Kathy Rowan, a professor in social science, we received approval from George Mason University’s IRB (Institutional Review Board) in August and launched a study to understand the impact and effectiveness of our educational offering to medical students. At present, we are in data collection mode and anticipate in 2022 we will transition to analysis of the data. If the conclusions are insightful, we intend to seek publication.
- Each Spring and Fall we reach out to medical school deans, updating them on our activities.
- Our target universe is approximately 160 continental U.S.-based medical schools – both their curriculums and student interest groups, and over 580 internal medicine residency programs.
- We gave 61 presentations in 2021, and have 13 already booked for 2022.
- Since the ASB started in the Fall of 2019, we now total 153 presentations, to approximately 6,900 students and physicians. A complete list of schools and resident programs can be found below.
- Of the 2021 presentations, roughly 20% of the presentations were within the curriculum; 75% to student interest groups, and 5% to residency programs.
The cornerstone of our effort is our group of wonderful patient speakers, who passionately volunteer their time to give back and share their stories of life with amyloidosis.
Our speaker group is diversified by geography across the continental U.S., by amyloidosis type, by organ involvement, by gender and age. This is a rather deep bench, but we have found it both helpful and necessary. Helpful in that we can maximize attendance if we work around the preferred dates and times suggested by the schools. Helpful in that we can match specific disease states with audience focus (e.g., a cardiac amyloidosis patient speaker to a cardiology student interest group). Also, helpful in rotating speakers and types of disease at each school, since we are regularly returning to groups which have overlapping students. And necessary in that periodically, a speaker’s personal situation may change and they need to step back either temporarily, or permanently. We are delighted that our group is fairly stable and increasingly seasoned and experienced in sharing their stories. That said, we are fortunate to have a steady pipeline of new speaker interest, which we spend time screening, qualifying and training to bring online – only if needed (so it’s rare we add new speakers these days). At present, we feel this is an appropriate number of speakers for our current and anticipated growth.
Thanks to two of our speakers who have extensive experience, we offer in-depth guidance for new speakers, and current speakers wanting a ‘refresh’ in the development of their presentation outline and rehearsal training for their delivery. In addition, prior to most virtual presentations we rehearse and test the new speakers’ audio and video technology. For those partaking, it has been an appreciated additional level of support and we believe is translating to a higher quality offering.
We are proud to have an impressive group of medical experts and influencers in the world of amyloidosis, some of whom are also patients, as advisors to support our initiative. Our advisors are active in our efforts and contribute their specialized expertise in a variety of ways, such as medical school introductions, grant requests, educational development, and patient speaker assessment/development. We are extremely grateful for their assistance and believe that, thanks to their contribution, the ASB will make an even bigger difference in the diagnoses of this disease. You can see our prestigious list of advisors on our website page www.mm713.org/speakers-bureau/
TESTIMONIALS – OUR TRUE REPORT CARD
Feedback from students and medical school professors has been extraordinarily positive. It reinforces to us that candid and authentic patient stories are a valuable complement to the medical school curriculum, strengthening the learning and deepening the durability for these future doctors about this disease. This is exactly why we do what we do. Here are just a few of the testimonials.
The opportunity for second year medical students to hear the story of a patient with amyloid is invaluable. The presentation addressed aspects of pathophysiology they are learning and the human side of medicine. This presentation format offered an excellent teaching opportunity to inform doctors-in-training about this serious disease. Our students gained insight into the patient’s journey through diagnosis, treatment and the challenges ahead. We all appreciated the patient’s generosity in sharing her experiences. Having patients teaching medical students about amyloidosis will have a lasting impact on our future doctors with increasing awareness of this disease and ultimately will help future patients. Theresa Kristopaitis, M.D., Professor, Assistant Dean for Curriculum Integration, Loyola University Stritch School of Medicine
Such a powerful presentation that I will carry with me throughout my whole career, no matter what specialty I go into! I not only learned the importance of keeping amyloidosis on my differential, but also the importance of really listening to your patients and working through the hard diagnoses together. Solana Archuleta, MD Candidate, University of Colorado School of Medicine
I had several students make comments after the conclusion of the presentation that it was the best, one even said ‘exceptional,’ presentations given at our school from a patient. The materials gave all of the students, including myself, a great introduction to some of the pertinent findings in patients with amyloidosis. Co-President of the Internal Medicine Interest Group, University of Arizona College of Medicine, Phoenix
Hearing Ed talking about his journey with Amyloidosis was an incredible experience that only further inspired me to want to be a better physician for my future patients. It is one thing to learn about a condition in the classroom, but hearing the real-world struggles with it from another human being provides a whole new perspective. Ed was open about his journey and shared his feelings during each step, giving us insight into what it is like to be a patient with Amyloidosis. I will take what I learned from this presentation and apply it in order to ensure that patients I see in the future do not have to deal with the same issues that Ed had to deal with. Gurkaran Singh, MD Candidate, University of Arizona College of Medicine, Tucson
Diseases such as amyloidosis are often managed by specialists, but it is important for primary care physicians to recognize these signs and direct these patients to these specialists. Increasing awareness of these diseases among all physicians will help patients reach an answer sooner and can have a significant impact on their lives. Yue Zhang, MD Candidate, Northwestern Feinberg School of Medicine
We are saddened that we lost our co-founder Charolotte Raymond earlier this year, losing her battle with AL amyloidosis. Charolotte was our true inspiration for the Amyloidosis Speakers Bureau, and we know her passion for educating future physicians will be our guiding light. To keep our patient-led focus, we were thrilled to have one of our speakers, Lane Abernathy, join our Operating Committee. Lane, an amyloidosis patient herself, brings wonderful energy, experience and passion to help manage our efforts. We feel thankful to have her with us.
An additional word about our growing list of passionate volunteers, the majority of whom are active speakers. They help our efforts across many aspects of our operations, from management, to speaker development, to research, and video production. Their dedication to our effort is a testament of their belief in what we are doing to educate areas of the medical community, and we thank them all.
We are pleased with all we have accomplished thus far, energized by the feedback, cognizant that we have much ahead, and hope we have made you proud. After all, we can’t do any of this without you! As always, we welcome any comments you may have.
Stay safe, happy holidays to you and your family, and all the best for a new 2022!
Mackenzie, Lane, and Deb
Operating Committee of the Amyloidosis Speakers Bureau, sponsored by Mackenzie’s Mission
Our initiative is being well received by medical schools across the country. Below is a list of schools we have presented to at least once a year, whether through their curriculum or interest groups. After that, is the growing list of internal medicine residency programs where we also have presented.
MEDICAL / D.O. SCHOOLS
- Albert Einstein College of Medicine
- Baylor College of Medicine
- California University of Science & Medicine, School of Medicine, San Bernardino
- Case Western Reserve School of Medicine
- Central Michigan University College of Medicine
- Chicago Medical School, Rosalind Franklin University of Medicine and Science
- Cleveland Clinic Lerner College of Medicine
- Columbia University Vagelos College of Physicians and Surgeons
- Drexel University College of Medicine
- Florida Atlantic University Charles E. Schmidt College of Medicine
- Florida International University Herbert Wertheim School of Medicine
- Florida State University College of Medicine
- Geisinger Commonwealth School of Medicine
- George Washington School of Medicine
- Icahn School of Medicine at Mount Sinai
- Lake Erie College of Osteopathic Medicine
- Lewis Katz School of Medicine at Temple University
- Loyola University Chicago Stritch School of Medicine
- Mayo Clinic Alix School of Medicine, Rochester
- Mayo Clinic Alix School of Medicine, Scottsdale
- Northeast Ohio Medical University College of Medicine
- Northwestern University Feinberg School of Medicine
- NYU Grossman School of Medicine
- Oakland University William Beaumont School of Medicine
- Quinnipiac University Frank H Netter MD School of Medicine
- Stanford University School of Medicine
- Touro College of Osteopathic Medicine in New York City
- Tufts University School of Medicine
- University of Arizona College of Medicine, Phoenix
- University of Arizona College of Medicine, Tucson
- University of California Irvine School of Medicine
- University of California San Francisco School of Medicine
- University of Central Florida College of Medicine
- University of Chicago Pritzker School of Medicine
- University of Cincinnati College of Medicine
- University of Colorado School of Medicine
- University of Connecticut School of Medicine
- University of Florida College of Medicine
- University of Hawaii, John A. Burns School of Medicine
- University of Illinois College of Medicine, Chicago
- University of Illinois College of Medicine, Peoria
- University of Illinois College of Medicine, Rockford
- University of Iowa Carver College of Medicine
- University of Kansas School of Medicine, Wichita
- University of Maryland School of Medicine
- University of Massachusetts Medical School
- University of Minnesota Medical School
- University of Missouri Kansas City School of Medicine
- University of Nevada Reno, School of Medicine
- University of Pittsburgh School of Medicine
- University of South Alabama College of Medicine
- University of South Carolina School of Medicine, Columbia
- University of Toledo College of Medicine
- UNLV School of Medicine
- Virginia Commonwealth University School of Medicine
- Wayne State University School of Medicine
- Wright State University Boonshoft School of Medicine
- Yale School of Medicine
- Central Maine Medical Center
- Meharry Medical College Program
- Michigan State University Program, Sparrow Hospital
- St. Francis Medical Center Program, Jersey Shore University Medical Center
- Texas Institute for Graduate Medical Education and Research (TIGMER) Laredo Internal Medicine Residency Program
- Western Michigan University Homer Stryker M.D. School of Medicine