Saturday, June 29, 2013

Dissecting Kawasaki Disease, Part 1: Misdiagnosis is Mandatory

According to the latest numbers available, Kawasaki Disease (KD) is still technically defined as a rare disease in most countries around the world.  We know that more and more children are being diagnosed with KD each year, but we don't know how many children are still going misdiagnosed.  The reasons for the misdiagnosing, while not always talked about, are clear.  The answer for this problem is simple; we need a diagnostic test for Kawasaki Disease.

Is Kawasaki Disease a rare disease?

While the definition of rare disease varies by country (US, EU, Canada, Japan all have their own definitions) the latest number of diagnosed cases of Kawasaki Disease still defines it as a rare disease.  In America, about 20 in 100,000 kids will be diagnosed each year.  According to this article in The Permanente Journal, 5,500 cases were estimated in the United States in 2009.  This 2012 article reported an incident rate in Japan of over 230 in 100,000 children under 4-years-old.

KD may still technically be rare, but numbers are rising all over the world. This 2009 article in the Journal of the American College of Cardiology described KD as "commonplace all around the world" and estimated there may have been as many as 1,000,000 cases of diagnosed and undiagnosed KD since it was first defined in 1967, with many more people affected before 1967.  Dr. Burns' Kawasaki Disease Lab goes even further by stating, "Kawasaki Disease is not a rare illness and the exact number of cases which occur in the United States has not been determined."

How do we know there are cases going misdiagnosed?

Many classic cases of KD start out as multiple misdiagnoses.  DSK's Kawasaki Disease Resource List enumerates many of these personal stories, like Cooper's story, Maya's story, Isaiah's journey, or Julian's saga.  My own daughter was misdiagnosed multiple times with both her bouts of KD. 

The numbers seem to show what these KD families have experienced.  This study, published in Pediatrics in 2005, found many children had to be seen by a doctor at least four times before a diagnosis of KD was made.  Even though over half of patients saw a doctor within the first 2 days of symptoms, only 5 of 106 children were given a diagnosis of KD at the initial visit.

In addition, we are now seeing adult patients who are experiencing coronary complications that presumably stem from an undiagnosed case of Kawasaki Disease they had sometime as a child.  An article in The Permanente Journal states, “many cases of fatal and nonfatal MIs in young adults have been attributed to 'missed' KD in childhood."  A January, 2013 article in Internal Medicine describes the case of a 72-year-old man who had giant coronary aneurysms, even though he had never been diagnosed with KD and was not symptomatic.  The authors conclude, "The present case suggests that there may be a substantial number of patients who have attained middle to old age with undiagnosed KD."

WHY does KD get misdiagnosed so frequently?

In the absence of a diagnostic test, KD is diagnosed by taking a thorough history and physical, and ruling out other illnesses.  In order to be diagnosed with KD, a child must run a fever for at least 5 days and have at least 4 of these accompanying symptoms: 1) rash; 2) swollen neck lymph nodes; 3) swollen hands and feet, red palms and soles; 4) bloodshot eyes; and 5) red, chapped lips and strawberry tongue.  Sounds pretty simple, right? Wrong.  Here are four reasons why it's more complicated.

1. The symptoms might not show up all at once.

Coronary artery complications (the most serious complication of KD) are greatly reduced when the treatment of intravenous immunoglobulin (IVIG) is given within the first 10 days of fever onset.  Unfortunately, sometimes it takes all ten of those days (or longer) for enough of the classic KD symptoms to show up.  Some symptoms may already be gone by the time others show up.  Sarah Chalke has mentioned that all of her son’s classic KD symptoms had started to dissipate by the time they saw a specialist on day 10.  If she hadn’t taken pictures of her son while he had the symptoms, the doctor may not have been able to diagnose KD. 

A 2007 article from Taiwan concluded that wide dispersement of the classic symptoms leads to more delayed-diagnoses beyond day 10, which leads to a higher incidence of coronary artery aneurysms (CAAs).  This excerpt from the American Heart Association statement on KD shows just how a misdiagnosis from delayed onset of symptoms can happen: "Children may present with only fever and a unilateral enlarged cervical lymph node. The rash and mucosal changes that follow often are mistaken for a reaction to antibiotics that are administered for presumed bacterial lymphadenitis." 

Many people like to talk about the peeling skin on the fingers and/or toes as a definitive symptom of KD.  Even though a majority of KD children do experience this desquamation, it usually occurs in the sub-acute or convalescent phase of the disease, after the 10-day window for effective IVIG treatment.  This article mentions that it is during this second phase of the illness that heart complications are likely to occur, so it is very important to diagnose KD before the fingers or toes start peeling. 

2. Many symptoms may not show up at all (Incomplete KD).

Incomplete Kawasaki Disease can be diagnosed in children who present with a fever and only 2 or more of the classic KD symptoms.  When so few classic KD symptoms show up, it should be no surprise that diagnosing incomplete KD is even harder than diagnosing complete KD.  Children with incomplete KD still have a risk for cardiovascular complications, including CALs, aneurysms, and heart failure. Children with incomplete KD have a higher risk of delayed diagnosis and were less likely to be treated with IVIG. Many studies (like this one and this one) have found an increased risk of cardiovascular complications, which is probably related to the other risk factors associated with incomplete KD.

3. Classic KD symptoms may look like other illnesses.

Many of the classic KD symptoms are also normal symptoms of other, less rare diseases.  My daughter was first diagnosed with a double ear infection, then strep, then scarlet fever, and they also thought the rash may be due to an allergic reaction to antibiotics.  I've heard other parents tell this tale of misdiagnosis so many times, it almost sounds like a mandatory step in diagnosing Kawasaki Disease. 

According to this site, "the rash may mimic common infections like measles, rubella, parvovirus and scarlet fever and may also resemble erythema multiforme.”  This 2005 Pediatrics article found instances of ultimate Kawasaki Syndrome first being diagnosed as “cervical adenitis, meningitis, pneumonia, appendicitis, or pyelonephritis."

4.  There may be additional symptoms that further complicate the KD diagnosis. 

My daughter had the worst cough she's ever experienced, both times she had Kawasaki Disease.  She would also have bouts with abdominal pain, vomiting, diarrhea, joint pain, lethargy, and extreme irritability.  Her personality literally changed during her illness and she reacted to things completely differently than she would normally.  These are all common symptoms for KD, and about a million other illnesses.

This 2013 article records a long list of "nonspecific clinical features," that may accompany the classic KD symptoms.  Some of these symptoms include irritability, uveitis, aseptic meningitis, cough, vomiting, diarrhea, abdominal pain, gallbladder hydrops, urethritis, arthritis.  Additional symptoms could be lethargy and myalgia.  Other symptoms (many very rare) reported by the American Heart Association include more irritability than with other febrile illnesses, facial nerve palsy, sensorineural hearing loss, hepatic enlargement and jaundice, testicular swelling, and pulmonary nodules.

Many of these symptoms can most definitely be mistaken for other more common diseases like, "influenza, upper respiratory infection, strep throat, or food poisoning."  Right Diagnosis points out that "Kawasaki disease is usually diagnosed by eliminating other disease possibilities, such as scarlet fever, cytomegalovirus infection and toxic shock syndrome”

Saturday, June 1, 2013

Closer to a Diagnostic Test for Kawasaki Disease

It’s been a big year for Kawasaki Disease, but this hasn’t always been the case.  KD has been a pretty steady bench warmer on the team of rare diseases.  Every once in a while, we’re called in to pinch hit.  We bat a marathon here, a House episode there.  But all jokes aside, Kawasaki Disease is just not very well known.  I’ve had nurses ask me what it is when giving them my daughter’s history.

According to Seattle Children’s Hospital, doctors in America diagnose approximately 4,000 cases of KD each year.  And this, of course, doesn’t consider the countless cases that go misdiagnosed.  The Kawasaki Disease Lab at UCSD tells parents as much by stating, “Kawasaki Disease is not a rare illness and the exact number of cases which occur in the United States has not been determined,” They estimate that 10 out of every 100,000 children will be affected and have observed KD occurring in “clusters or localized outbreaks - usually in the winter and spring.”  I’ve seen other statistics as high as 19 or 20 out of every 100,000. 

The only time I’d ever heard of this illness before 2008 was in an episode of the TV show ER.  Then my 22 month old started displaying the classic symptoms of Kawasaki Disease and I got very familiar very quickly.  If that wasn’t enough, I became even more intimately involved when she was diagnosed again at 6 years old with Recurrent Kawasaki Disease.

From a medical standpoint, KD is defined as a pediatric self-limited vasculitis that is the leading cause of acquired heart disease in children.  The complication that raises the most concern is inflammation in the coronary arteries of the heart.  If left untreated, KD can lead to coronary artery aneurysms in up to 25% of reported cases.  When treated with Intravenous Immunoglobulin (IVIG) within the first 10 days after symptoms start, chances of heart complications are reduced. The primary symptom of KD is a fever that lasts more than five days.  The other symptoms are visually alarming and include red and swollen feet and hands, red eyes, red/chapped/cracked lips, strawberry tongue, rash, and swollen lymph nodes in the neck.

From a kid engulfed in its blaze standpoint, KD is defined as pain - an awful, burning pain.  My daughter has a hard time describing it.  She will talk about how much it hurt, but can’t tell me where.  It’s like it hurt everywhere at the same time, and then it hurt worse because someone was always “doing something to me.”

From a parent sitting helplessly at the foot of the bed standpoint, KD is defined as watching my child burning from the inside, out.  Think about the last time you had a sunburn and how much that hurt.  Now imagine having a sunburn on the inside of your body.  It’s like every cell in her body was on fire, and nothing could quench it.  You want desperately to soothe your baby, and your baby wants so desperately to be soothed.  But there is no soothing.  There is no comforting.  There is only burning. 

And the hits just keep on comin’.  No one knows what causes KD.  There is no diagnostic test for KD and no test to show it’s “cured.”  No one knows how to prevent Kawasaki Disease and many cases of a-typical or incomplete KD are never diagnosed.  Many other cases of KD aren’t diagnosed within the 10 day window, which often leads to further complications. 

But, I don’t mean to be quite so dire.  Even though there are still many confusing questions, the quest for answers has never been more fervent than in the past few years.  In November of 2011, a group of Singapore scientists published a study in Nature Genetics that identifies a specific gene (a protein called FCGR2A) associated with an increased risk of KD.  That same month, a group of doctors, including Dr. Burns, published a study that suggested the environmental trigger for KD could be wind-borne. 

Many more hospitals are now focusing in on Kawasaki Disease.  Seattle Children’s Hospital’s Portman Research Group Kawasaki Disease Program is currently trying to understand and improve the treatments for KD and is also pursuing a hypothesis that soy consumption may be associated with KD risk.  Rady’s Children’s Hospital’s Kawasaki Disease Clinic follows the status of 1,200 KD patients in San Diego and treats 80 to 90 cases every year. Dr. Burn’s Kawasaki Disease Lab at UCSD has information about 12 separate studies on their website.  Many of the research studies conducted by these groups are still accepting participants. 

There have also been media sightings of a slightly flashier nature.  In April of 2011, chef Nate Appleman chose the Kawasaki Disease Foundation as his charity when he won the Food Network’s Chopped All-Star competition because his son had been affected.  After his own son recovered from KD, Gary Busey joined the campaign and started The Busey Foundation.  Busey went on (and was fired from) the latest season of Donald Trump’s Celebrity Apprentice, in the hopes of winning money for KD. 

The biggest spotlight yet came on March 8, 2013, when Sarah Chalke guest starred as the mom of a little boy sick with Kawasaki Disease on an episode of Grey’s Anatomy.  The prominent storyline not only mentioned the classic symptoms of KD, but also illustrated the kind of cat-scratch fighting a parent often has to endure when Kawasaki Disease invades their child and how important it is to listen to your intuition when it comes to the health of your child. 

The wonderfully hilarious actress got serious when she opened up a small window into her private life and told the world that her own son was a Kawasaki Disease survivor.  Ms. Chalke explained that after meeting other KD survivors and their parents, she felt compelled to join the KD awareness campaign.  She approached Grey’s creator, Shonda Rhimes, with the KD storyline idea and made the round of popular talk and news shows, giving millions of people their first glimpse at this unusual disease. 

Promising research and a larger public spotlight have now collided into the most hopeful KD news yet. We may soon have a diagnostic test for Kawasaki Disease! The combined efforts of Dr. Burns' team, The Kawasaki Disease Foundation, and Sarah Chalke have culminated into the Kawasaki Disease Challenge Fundraiser on  On the fundraiser’s website, Sarah Chalke writes:

When my son had Kawasaki Disease and was misdiagnosed for ten days, I can’t tell you how many times I said, “I just wish there was a test. A test that could tell us if this is KD.”

And now there might be.  A team of doctors at Stanford University and UCSD have devised a prototype for a diagnostic test. This is a huge deal. This test could be 95% accurate but it needs to be tested for two years before it can be used. We NEED this test because of the ticking clock to get treatment to prevent heart damage that can lead to a heart attack.

The disease that didn’t even get its name until 1967 may yet be considered a rare childhood disease to some and many have still never even heard of it, but once Kawasaki Disease enters your life, you never forget it.  So many moms, just like myself, have gone through this nightmare and felt compelled to reach out and make sure other parents have indeed heard of Kawasaki Disease.  Sarah Chalke is one of these moms.  We want the misdiagnosing to stop.  The best way to do that is with a diagnostic test.  We’re now closer than we’ve ever been before.  Please go to Sarah Chalke’s Kawasaki Disease Challenge today.  It has already raised over $5,000 in its first 2 days, and the Gordon and Marilyn Macklin Foundation will match dollar for dollar up to $100,000! Let's raise $200,000 for a Kawasaki Disease diagnostic test.  Donate.  Share.  Tell your coworker over coffee.  Mention it to your neighbor over the fence.  Save a heart.  Save a life.


For an organized list of all the links in this article and many more, please check out my KD Resource List.

Sunday, May 12, 2013

Sunday, March 31, 2013

Grey's Anatomy Takes Kawasaki Disease To Heart

*** Caution! Spoiler alert! This post describes in great detail narrative from Grey's Anatomy, Episode 9x19, "Can't Fight This Feeling."  If you haven't watched this episode yet, and you don't want to know what happens, then stop reading.  Seriously.  Walk away from the post.  Do not pass go.  Do not collect 200 dollars.  You have been warned. ***

Watching Grey's.  Me: You're my Kawasaki baby.  Her: I'm your Kawasaki survivor. 

When I first found out that Grey’s Anatomy was going to be doing an episode featuring a child with Kawasaki Disease, excited doesn’t begin to cover what I felt.  I’m a huge Grey’s Anatomy fan; one of those over-the-top geeks who has seen every single episode more than 5 times, type of fan.  I also happen to be a Kawasaki Disease awareness advocate since my daughter has survived two different cases of KD.  This was like every holiday rolled into one.

Then I found out that Sarah Chalke, who would be guest-starring in the episode as the KD mom, initially brought the idea to Grey's creator Shonda Rhimes because Sarah's own son had been diagnosed with Kawasaki Disease two years prior, and she wanted to raise awareness for the sake of other parents and children.  After speaking at a KD fundraiser and hearing other KD parents' stories, Ms. Chalke said, "...I had never met anyone who had had it before. They were all so brave, and the experience galvanized me to feel like we have to do something; we have to do whatever we can to raise awareness for this rare thing that there is a treatment for but that is so often misdiagnosed."

Ms. Chalke seemed extremely committed to the fact that this was to help real-life parents.  When asked if she would play the mom in the episode, she said, "Thank you so much, I can't put into words how much it means to me that we're going to do this episode because it's going to raise awareness and it's going to save kids." I had very high hopes that this would be a great boost to the KD cause because I figured an actual KD mom wouldn’t agree to do something that didn’t show the reality of this disease.

Boy, was I right.  While watching the episode, aptly titled “Can’t Fight This Feeling,” I remember posting on Facebook that it was getting a little hard to watch.  Looking back on it, that wasn’t exactly true.  It was hard watching it without having an emotional reaction to it, and I did end up crying through most of the scenes with Sarah Chalke.  But the emotional reaction wasn’t exactly bad.  It was exhilarating.  I felt a weird sense of vindication watching it, like I wanted to scream at the TV, “YES! Exactly! That's what happened to us! That’s exactly what I said!”

The episode introduces us to Chalke's character, Casey, and her son, Parker, who has been sick with a fever above 103 for over a week and has been diagnosed with a virus.  But Casey has a strong feeling that it isn't a virus, and when Parker develops a rash, she brings him back to Grey + Sloan Memorial Hospital ER to be reevaluated.  His rapid strep test comes back positive, and Parker is again sent home with more medicine (antibiotics).  But Parker doesn't get any better, and Casey again brings him back to the ER, this time revealing that this is the 3rd medical establishment to try and bully her into thinking she's wrong to question their diagnosis.

No longer willing to back down, Casey voices her feelings loud and clear: "You either don't care about my son or you don't believe me.  Either way, you suck, and I want someone else.  FIND ME ANOTHER DOCTOR!"

Enter Dr. Meredith Grey.  After an insulting visit from a psychiatrist, Casey's pleas are finally heard by someone willing to listen to her.  Dr. Grey tells Casey she believes her and will admit Parker for more tests.  Even after further testing and a CAT scan show nothing new, she listens with an interested ear as Casey describes the different diseases that she has researched online that seem to fit Parker's symptoms - one of which is Kawasaki Disease.  Dr. Grey doesn't talk down to Casey when she explains why all of these diseases have been ruled out.  Casey does not stop pushing and insists there has to be something.  She knows her child and her gut is telling her this is not strep.  Dr. Grey, a mother herself, again runs more tests.

Still nothing; there's nothing surgical and labs all come back clean.  After exhausting all avenues, Dr. Grey is convinced it's strep and plans to discharge Parker.  Casey still doesn't give up.  She again tries to convince Dr. Grey that there is more going on than the labs show.  She pleads:
“I know I keep saying this and I know it’s crazy, I mean I can hear myself sounding crazy.  But this feeling won’t go away.  This feeling that there is something wrong with him.  And I know you’re telling me there is nothing wrong with him and that I should believe you because you’re a doctor and I’m just a waitress.  But how do I ignore this? How do I ignore my gut telling me that there is something seriously wrong with my son?"
Casey is so convincing that Dr. Grey wants to go over all the findings one last time with intern, Jo, before discharging Parker.  This takes long enough for updated labs to come in, which show that Parker's initial strep test is a false positive.  Meredith runs with this news, examines Parker one last time, finds conjunctivitis, and finally diagnoses Parker with Kawasaki Syndrome.  Parker is started on the standard treatment of IVIG.  Because Casey pushed so hard, and because Dr. Grey listened to her, Parker's IVIG was started within the 10 day window of fever onset, which greatly reduced his chances of further heart complications.

I think that most KD parents, like myself, were very happy with how the episode played out, but it is important to note that there were some disappointments.  Some thought it just wasn’t enough - not enough time devoted to the KD storyline, not enough specific information given about the disease.  I will say that from both medical and filmmaking standpoints, that while the medicine wasn’t spot on accurate, I think they did a pretty great job.

Some people were upset that the Kawasaki Disease storyline wasn't the main focus of the episode, but I thought it gave more suspense to Casey and Parker's plight.  It also added to the realism that abounded throughout the narrative.  Most urban ER's are brimming with emergencies and you have to make sure your child isn't lost in the shuffle.  Since Kawasaki Disease is so often misdiagnosed as a simple virus, your child can easily be overlooked in the sea of seemingly sicker patients.  Add to this the urgency involved in getting KD diagnosed and treated within the first ten days, and all of a sudden you're dealing with a ticking time bomb that only seems audible to your own ears.

It also sounds like some people wanted a classic presentation of KD, where all of the tell-tale symptoms (Swollen lymph nodes in neck, rash, red eyes, hands, feet, lips, and tongue) were present and diagnostic testing turned out the predictable high platelet count and SED rate so typically seen with Kawasaki Disease.  I think it is important to remember that this isn’t an educational special on PBS, it is a hit television series on a major network.  Hit television shows rely on ratings - ratings rely on drama - and a classic presentation of Kawasaki Disease in which all the symptoms are present, making it a pretty quick and easy diagnosis, does not drama make.

This is why I believe Grey’s Anatomy chose an a-typical/incomplete presentation of Kawasaki Disease.  Not only did it give the storyline more drama, it gave a more realistic view of the disease, in my opinion.  If they had presented a classic case of KD that was easily diagnosed by the doctors, I know that I would not have been the only one throwing my arms up at the TV and questioning, “Seriously? That’s not what it’s like at all! That was way too easy!”

Grey’s Anatomy’s depiction of Kawasaki Disease was so chillingly real, I can pretty much make side-by-side comparisons with my child's own KD story.  I literally heard my words coming out of Sarah Chalke’s mouth.  What seems to be as common to Kawasaki Disease as chapped lips or strawberry tongue, is the amount of convincing parents have to do to prove their child has more than just a virus.

One can find many instances of standard KD awareness information throughout the episode.  Dr. Grey does mention the symptoms of strawberry tongue, peeling skin, and red eyes as symptoms of Kawasaki Disease.  The absence of these symptoms in this case is a major reason why Dr. Grey doesn’t initially suspect KD.  Later in the episode, conjunctivitis is recognized, evidencing that many KD symptoms take a long time to appear.  They also stress how important it is to start IVIG within the first 10 days of fever onset to lower the risk of permanent heart damage.

What the writers of Grey’s Anatomy executed beautifully, was the sheer will and determination it so often takes on the part of the parent, to get their child diagnosed with Kawasaki Disease.  Only 19 out of 100,000 American kids will get Kawasaki Disease.  It often presents with symptoms that suggest a plethora of other illnesses.  There is no diagnostic test you can give specifically for Kawasaki Disease.  Many of the secondary symptoms of KD rely heavily on the parents’ shoulders to identify.  No doctor is going to know that a child is having personality changes without the parent telling them.

After showing Casey her son's echocardiogram, Dr. Grey shows her a slip of paper that Casey had given her earlier.  A slip of paper with her son's diagnosis of Kawasaki Disease written on it.  Meredith tells Casey:

“Do you remember this? Parker has Kawasaki Disease.  You fought for your son.  You didn’t give up.  You saved his life today.  You were right.”
There are other points that show just how seriously Shonda Rhimes and company took this issue.  We got Meredith Grey as our doctor.  The doctor the show is named after, THE doc of Grey’s Anatomy, was the one to take on Kawasaki Disease.  We also got very strong references in both the opening and closing scenes. 

In the opening scene, Meredith knows her daughter is up even without hearing her.  She just knew.  In voice-over, she tells us that to cut out an aneurysm (ironic example), you’ll need “confidence, an eleven blade, and some really good instincts.”  It may not require a scalpel, but I can say from personal experience that being a KD parent takes a whole lot of confidence and good instincts.

In the closing scene, Meredith checks on Parker and finds him sitting up and coloring.  Casey mouths the words “thank you,” and holds up a picture Parker has drawn.  Parker is already on his way back to being himself, as evidenced by the relief swimming in Casey’s eyes.  Dr. Grey’s voice-over confirms what every KD parent learns the hard way: “Try as you might, you can’t ignore your instincts.”

Meredith has decided to go the extra mile in an effort to protect her daughter’s health by getting both her daughter’s and her genes mapped.  “I wanna be able to fight for my kid...” Then in voice-over: “It’s like they say, always follow your intuition.”  Every single time I’m giving a mom advice on KD, I mention intuition.  Every.  Single.  Time.  In lieu of an actual diagnostic tool, it seriously seems like the most important tool in diagnosing Kawasaki Disease.  Someone is going to tell you no.  It’s just going to happen.  And you have to have the strength to listen to your intuition that is screaming at you - YES!

That’s only the second to last line in the episode, though.  Ever appreciative of music’s power, this episode of Grey’s ends with a song lyric.  I haven’t been able to locate the details of the song yet, but from what I can tell the lyric is “that I wasn’t alone.”  For me, this is not only apropos for KD families, but for the entire KD community as a whole.  I hear it from KD parents all the time - how lonely it is.  It is so important to remember that you are not alone.  Other KD parents know exactly how you feel and what you are going through, and we are here to help.

So much has changed and grown, even since my daughter’s first bout with Kawasaki Disease.  There now abounds a wealth of information in the form of websites, blogs, message boards, and social media sites for people looking for information on Kawasaki Disease.  Sarah Chalke tweeted during the episode that she kept going back to the Kawasaki Disease Foundation website as a source when her son was sick.  No one knows how scary Kawasaki Disease is more than a parent who has seen it in their child's face and no one is ready and willing to help more than a KD parent.  I am forever grateful and proud to call myself a member of this community.

I’m also grateful for a TV show that has brought such positive attention to a cause dear to my heart.  Thank you to Sarah Chalke, Shonda Rhimes, and everyone involved in the making of Grey’s Anatomy.  I can’t fight this feeling that Grey’s just saved the lives of countless kids.

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