FY 2022 VA-Funded Projects

Shocking Cause Of Man's Cardiac Arrest

Internal medicine and rheumatology specialist Siobhan Deshauer, MD, takes us through a medical case study: cardiac arrest after red meat consumption.

Following is a transcript of the video (note that errors are possible):

Deshauer: Hey, guys. I'm Siobhan, an internal medicine and rheumatology specialist. Today, I'm going to tell you about Tom, a retired high school teacher who ate a strict carnivore diet. He went all in on this meat diet, expecting health benefits, but instead it almost cost him his life.

Tom and his wife, Patty, recently returned from a fishing trip bored of eating fish day after day. Tom went to the local farmers' market to prepare for a red meat feast. When he got home, he fried it all up and they enjoyed a delicious dinner together. After dinner, Patty went out to her book club meeting and Tom went to the living room to watch the football game. While Patty and her friends were discussing a tragedy in their book, The Covenant of Water, they were blissfully unaware of a tragedy that was unfolding back at home. Tom was fighting for his life.

About an hour later, Patty returned home to a horrifying sight. Tom, who seemed perfectly fine after dinner, was now slumped over the side of the couch, unresponsive and barely breathing. In a panic, Patty called 911. After explaining the situation, the operator calmly walked her through what to do, step by step. She pressed her fingers into Tom's neck and couldn't feel a pulse. She wasn't sure if he was still breathing. The operator told Patty to bring Tom to the ground and to start CPR.

Fifteen agonizing minutes later, she finally heard the sirens approaching. Covered in sweat and tears, she yelled for them to come to the living room. Miraculously, when the paramedics checked, Tom had a pulse. It was weak and rapid, but it was there.

Within minutes, they were speeding down the highway towards the hospital. Tom was in critical condition. His blood pressure was perilously low. His heart was racing and his oxygen levels were dropping.

As they rushed him into the hospital, the medical team was ready. In these moments, when you walk into a room and you see a crashing patient, it's like time slows down as your mind is filtering through a huge amount of information in a matter of seconds. The emergency doctor's eyes darted from Tom to the cardiac monitor.

Tom was conscious and moaning, immediately giving them some reassurance that his airway wasn't blocked. But his breathing was shallow and his oxygen levels wouldn't budge above 85%, even though he was receiving the maximum amount of oxygen. His blood pressure was low, only 77 over 50, despite having an IV running fluids in as fast as possible.

We have two issues: low oxygen and low blood pressure. Our priority is getting his oxygen levels up, but in reality we have to work on both at the same time. Knowing that Tom had just had CPR for 15 minutes, where Patty was pushing on his rib cage hard enough to compress his heart and circulate his blood, it's very likely he has broken ribs. The sharp edges of a broken rib can puncture a lung and cause it to collapse.

The doctor listened to Tom's lungs carefully and he heard normal breath sounds on both sides of the chest, so his low oxygen levels probably aren't due to a completely collapsed lung. Tom winced in pain every time he was moved and even when the stethoscope was placed on his chest, so a stat portable chest X-ray was ordered, which confirmed that he did have multiple broken ribs from the CPR and a possible pneumonia on the right side.

Both of these findings could explain his low oxygen levels. Not only does a pneumonia prevent air from entering part of the lung, but Tom was in so much pain from the rib fractures that he couldn't take a proper breath in.

In this situation, when you have a patient who is critically ill, who has low oxygen levels, who just recently had a cardiac arrest, and who is still drowsy, it's critical to get control of their airway. Tom's doctors decided to intubate him, which means putting a breathing tube down his throat.

Now, for this procedure, we usually sedate patients, but a sedating medication can drop Tom's blood pressure even further, which could be deadly. He had already received 3 liters of IV fluids and his blood pressure hadn't budged. To put that into context, the average man only has 5 liters of circulating blood so that's not a good sign.

They need to intensify Tom's treatment with a medication called norepinephrine. Norepinephrine is a medication that increases the patient's blood pressure by causing their blood vessels to constrict, similarly to the way your body reacts to adrenaline in a fight-or-flight scenario, and it worked. Tom's blood pressure rose to a safer zone within minutes. Now, Tom's doctors were able to safely perform a rapid sequence intubation and hook Tom up to life support.

This is really how it goes in a critical, life-threatening scenario. You always have to stabilize your patient first and often with very little information. Then you have time to run tests and figure things out, and really nail down the diagnosis. Now, the question is why is Tom so sick? What's going on here and can we fix the problem?

At this point, all we know is that Tom is in shock. Your organs need a constant supply of oxygen and nutrients. If something happens to disrupt the amount of blood flow going to your organs, then your body goes into a state of shock. The challenge is there are many different types of shock and they are often treated differently. If you give the wrong treatment, it could be fatal.

Tom's blood work came back showing an elevated lactate level, more evidence that he is in shock and that his organs aren't getting enough oxygen. It's similar to when you sprint and lactic acid builds up in your muscles.

His blood work also shows an elevated white blood cell count and C-reactive protein, which suggests there is some kind of infection or inflammation. Remember, we did see a possible pneumonia on his chest X-ray and that could explain his blood work. For now, that's going to be our leading diagnosis, pneumonia causing septic shock.

But how does an infection lead to shock and such a shockingly low blood pressure? This is a fascinating topic and, to put it simply, in septic shock your immune system overreacts to an infection, flooding your body with chemical signals that cause your blood vessels to dilate and become leaky. That's what causes your blood pressure to drop.

We need to act quickly. The moment we even consider this could be septic shock we have to give antibiotics immediately. That's because every hour we delay giving antibiotics a patient's risk of dying increases by 8%, so now Tom's receiving IV fluids, norepinephrine, antibiotics, and corticosteroids to treat possible septic shock.

But hold on, things aren't quite adding up for me. Tom went from being completely fine to having a cardiac arrest just a few hours later. It's not really the timeline I would expect for septic shock, so what else could it be? In a middle-age man, we have to think about a cardiac cause. Could this have been a heart attack or an abnormal heart rhythm? It doesn't look like it. He had a normal echo and a normal ECG.

What about a pulmonary embolism? A large enough blood clot in his lungs could definitely drop his oxygen levels and his blood pressure. But his CT angiogram didn't show any signs of an obstruction. We can also cross off hypovolemic because he is not bleeding and he has no reason to be dehydrated, so we're left with the category of distributive shock. It still could be septic shock, but it just doesn't quite fit.

Tom's doctor went back to speak with Patty. He wanted to hear every detail she could remember. Patty took a deep breath and thought back to dinner. Tom had been feeling well that day. He hadn't been coughing or feeling sick. They had the exact same meal countless times before and he never had any issues.

Then, Patty paused. She recalled that when she was heading out for her book club Tom had mentioned that he was itchy and she just told him to put on some cream. Itching, interesting. Could this have been the first sign of an allergic reaction? Anaphylaxis is a severe, life-threatening allergic reaction and as you might remember it's one of the causes of distributive shock.

But that would be unusual, too. Anaphylaxis usually happens quickly when you're exposed to something you're allergic to. A classic example would be a bee sting that rapidly leads to hives and swelling of the lips and the throat. Any "Bridgerton" fans out there will know what I mean.

But anaphylaxis isn't always so obvious. There is a huge range of potential symptoms and rarely it is possible to have a delayed anaphylactic reaction. Tom's doctors sent off blood work looking for signs of an allergic reaction and it's a good thing they did because his tryptase level came back five times the upper limit of normal.

Tryptase is an enzyme made by your immune system. Think of it like an allergy alarm bell. When your body detects something it's allergic to, special cells will release tryptase to sound the alarm and it's not usually elevated in septic shock. Even though we saw that possible pneumonia, we can be pretty confident that Tom is actually in anaphylactic shock.

If there is one thing I really want you to remember, it's that you treat anaphylaxis with epinephrine, which is what's in an EpiPen. That's what they did. Tom's doctors quickly switched him from norepinephrine to epinephrine.

But we're not finished yet. What could have possibly caused the reaction? It doesn't sound like he was swarmed by bees and he hasn't added anything new to his diet. If we don't know the trigger, how can we prevent it from happening again? Tom's doctors called the allergy specialist to come investigate. The allergist on call spoke with Patty and she heard the same story: sausage, hamburger, itching.

But our next question was a surprise. Had Tom been exposed to any ticks recently? As you may recall, Tom and Patty had been on a fishing trip a few weeks ago and he had found a lone star tick in his belly button and he wasn't sure how long it had been there.

Why is that relevant? Well, when the tick burrowed into Tom's skin it injected a molecule called alpha-gal right into his bloodstream and alpha-gal is a carbohydrate that's found in all mammals, except humans and higher primates. When Tom's immune system came in contact with alpha-gal, it identified it as foreign and kind of freaked out and started creating IgE [immunoglobulin E] antibodies. This is a critical point because IgE antibodies are responsible for anaphylactic reactions.

Over the next few weeks, Tom's immune system pumped out tons of these antibodies, so they were ready and waiting for alpha-gal, which flooded Tom's system when he had his red meat feast. At this point, an overwhelming immune reaction took place. Chemical signals like histamine were released in huge quantities, which caused his blood vessels to dilate and his blood pressure to drop. That's what caused Tom to go into shock.

We've got a great theory, but how do we prove it? Fortunately, there is a blood test to detect IgE antibodies against alpha-gal and Tom's levels were sky-high. We finally have our diagnosis. Tom has alpha-gal syndrome.

Siobhan Deshauer, MD, is an internal medicine and rheumatology specialist in Toronto. Before medicine, she was a violinist, which is why her YouTube channel is called Violin MD.

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Newer Rheumatoid Arthritis Drugs Work Well In The Real World

They've been approved for the US market since 2012, but Janus kinase (JAK) inhibitors are still the new kid on the block in terms of rheumatoid arthritis treatment. As such, the real-world evidence on this class of drugs is scarce compared to established treatments.

Now, researchers in Japan have taken an important step in changing that, using extensive patient data to show that JAK inhibitors are as effective a first-line treatment as existing medications, even though they're still largely considered a back-up plan if others fail.

"Real-world patients have different characteristics compared with the patients recruited in randomized controlled trials," the researchers note in the study. "Therefore, it is important to investigate the effectiveness and safety of JAK inhibitors in real-world settings."

Analyzing the data of 622 patients from the ANSWER cohort study, the scientists evaluated four JAK inhibitors; baricitinib (BAR) known in the US as Olumiant, tofacitinib (TOF) known as Xeljianz, and upadacitinib (UPA) known as Rinvoq. They also assessed peficitinib (PEF), or Smyraf, which is predominantly available in Japan and Southeast Asia.

"We found that most patients have success with these medications, and the efficacy and safety of each of these JAK inhibitors was not significantly different in the treatment of rheumatoid arthritis," says lead author Dr Shinya Hayashi, a arheumatology specialist at Kobe University. "These medications offer options when biologic disease-modifying antirheumatic drugs (DMARDS) have failed."

JAK inhibitors interrupt signals that cause inflammation. With rheumatoid arthritis, the body makes too many proteins called cytokines, which play a key role in inflammation. When these cytokines attach to immune cell receptors, the message is given to make even more of the proteins. JAK inhibitors block this messaging pathway, which calms the immune system response and, in turn, relieves painful arthritis inflammation.

JAK inhibitors are also effective for treating skin conditions such as eczema and vitiligo, and there are now around a dozen different types approved for use in the US.

Traditionally, the first treatment for rheumatoid arthritis is usually injections of methotrexate, a DMARD. Then, if the drugs don't do the trick, or they come with too many side effects, a patient may then be switched to an orally administered JAK inhibitor. The patients in the study had received the JAK inhibitor following poor responses to DMARDs.

But because they're a newer class of medication, much like glucagon-like peptide 1 (GLP-1) agonists for weight loss, they are often considered a 'when all else fails' plan B. Doctors generally prescribe DMARD biologics first, because there's more long-standing research available on these.

The researchers, assessing the data with various pain-indicator surveys, found that around 90% of the 622 patients were still taking their JAK inhibitors six months after beginning them.

Overall, about one-third of patients saw their arthritis enter remission within the six months, with more than 80% experiencing 'low disease activity,' in which symptoms were largely controlled.

The hesitancy in JAK inhibitors uptake has been due to concerns about real-world efficacy beyond controlled trials – which this study lays to rest – and potential side effects.

While the researchers say the study has its limitations, such as six months being a short time frame for long-term side effects, and a lack of studies comparing all classes of drugs, the four JAK inhibitors performed similarly to each other, and their effectiveness proved to be on par with existing DMARDs. A previous clinical study, showed they had comparable efficacy to TNF inhibitors, another type of DMARD.

Around 1.3 million Americans have rheumatoid arthritis, a chronic autoimmune condition that can greatly diminish quality of life and prove stubborn to treat.

The study was published in the journal Rheumatology.

Source: Kobe University Graduate School of Medicine via Medical Xpress

Anti-rheumatic Drugs Could Have A Preventive Effect On Autoimmune Thyroid Disease

Anti-rheumatic drugs used for rheumatoid arthritis might prevent the development of autoimmune thyroid disease, according to a new observational study by researchers from Karolinska Institutet published in the Journal of Internal Medicine.

It is well known that patients with rheumatoid arthritis are at increased risk of autoimmune thyroid diseases such as Hashimoto's disease and Graves' disease. While patients with RA are usually treated with immunomodulatory drugs that affect the immune system, such drugs are rarely used in autoimmune thyroid diseases. Instead, such patients are treated with thyroid hormone to compensate for the changes in normal thyroid function that accompany autoimmune thyroid disease.

The researchers in the current study wanted to investigate whether immunomodulatory drugs that reduce inflammation in the joints of patients with RA might also reduce the risk of these patients developing autoimmune thyroid disease. Previous studies in mice suggest that so-called DMARDs, a type of immune-modulatory drugs used to treat rheumatoid arthritis, can reduce inflammation in the thyroid gland. Still, knowledge of whether this effect also applies to humans is limited, according to the research team.

The researchers used data between 2006 and 2018 on over 13,000 patients with rheumatoid arthritis and their treatment, as well as data from over 63,000 individuals in a matched control group without rheumatoid arthritis.

The researchers found that the risk of developing an autoimmune thyroid disease among RA patients was lower after their onset of the rheumatic disease than before diagnosis.

The most pronounced reduction in the risk of autoimmune thyroid disease was seen in patients with rheumatoid arthritis treated with immunomodulatory drugs or 'biological DMARDs'. In these patients, the risk of autoimmune thyroid disease was 46 percent lower than in the control group without rheumatoid arthritis.

"These results support the hypothesis that certain types of immunomodulatory drugs could have a preventive effect on autoimmune thyroid disease," says Kristin Waldenlind, researcher at the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, specialist in rheumatology at Karolinska University Hospital and first author of the study.

Our results do not prove that it is the treatment with immunomodulatory drugs that led to the reduced risk of autoimmune thyroid disease, but provide support for this hypothesis. The results, if they can be replicated in further studies, open up the possibility of studying more directly in clinical trials whether the immunomodulatory drugs currently used for rheumatoid arthritis could also be used for the early treatment of autoimmune thyroid disease, i.E. For new areas of use of these drugs, known as drug repurposing."

Kristin Waldenlind, Study's First Author

The Swedish Research Council, the Swedish Heart-Lung Foundation and Vinnova mainly financed the study.

Source:

Journal reference:

Waldenlind, K., et al. (2023) Disease-modifying antirheumatic drugs and risk of thyroxine-treated autoimmune thyroid disease in patients with rheumatoid arthritis. Journal of Internal Medicine. Doi.Org/10.1111/joim.13743.

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