Sunday, November 12, 2017

2017 Hereditary Amyloidosis meeting - Sunday

Today's post will cover the last day of the 2017 Hereditary Amyloidosis support group meeting in Chicago. The Sunday agenda is always just half a day, with the doctors answering questions submitted by attendees. The session is moderated by Dr. Gertz, who goes through the stack of questions and decides which questions to ask and which doctor or doctors to give the questions to. I have submitted questions in the past for the Sunday session, and I submitted a two-part question this time as well.

If you recall from my blog post about the Saturday presentations, Dr. Benson did discuss the difference in numbers (when referring to a specific mutation) when the full length of the protein (including the signal peptide) is considered vs. when the length of the mature protein is considered (not including the signal peptide). He discussed the length of the signal peptide for transthyretin (TTR) which is 20, meaning you just add or subtract 20 to get from one number to the other. But he did not mention the signal peptide length of the other proteins that can cause hereditary amyloidosis, such as fibrinogen, lysozyme, apolipoprotein, or gelsolin. When the report from the nomenclature committee came out last year I looked up somewhere that the length of the signal peptide for fibrinogen was 19, not 20 like TTR. I don't recall what the length is for the other rare ones, but if I remember correctly they are not 20 either. Since I would not want anyone leaving the meeting thinking their signal peptide length was 20 when it is really something else (knowing very well that I was probably the only person there who cared), I submitted two related questions:

Question 1: What is the signal peptide length of the amyloidogenic proteins other than TTR?

I was hoping the question would go to Dr. Benson and he would say the signal peptide length is 20 for TTR but it is 19 for fibrinogen, xx for apolipoprotein, yy for lysozyme, etc., and then talk about how confusing it will be to get everyone on the same page. That leads to my second question:

Question 2: Will Dr. Benson promise not to retire before everyone is comfortable with the new recommendations of the nomenclature committee?

For those of you who don't know, Dr. Benson is probably past normal retirement age. He received his bachelor's degree in 1961 and his MD in 1965, so he has been practicing medicine for over 50 years. Given his expertise and experience, especially in discovering many of the mutations that cause hereditary amyloidosis (including some of the fibrinogen mutations), his retirement will likely have a huge impact on both patients and doctors in the amyloidosis community. So my second question was obviously intended to bring a little levity to the proceedings. Dr. Benson has a very quick wit and a dry sense of humor, so I felt certain he would have an entertaining answer to the question.

With so many attendees at this year's meeting, Muriel announced before the session started that if they did not get to all of the questions they would try to get answers later and make those answers available in a document they would let everyone know about. Typically she will publish all of the answers from the Q and A session, but as of this writing she has not. If and when she does I will update this post and also mention it in the next new post.

So the Question and Answer session starts Sunday morning, with Dr. Gertz reading the questions out loud and then having the appropriate doctor answer them. As usually happens during the Sunday session, some doctors need to leave before the session is over at noon in order to catch their flights back home. As the morning went on, a few doctors got up from their seats in the front of the room and started walking down the center aisle toward the exit at the back. Dr. Gertz would notice the doctor leaving and say something like "Thanks to Dr. So-and-so," prompting the audience to give that doctor a round of applause. Well, much to my surprise, Dr. Benson got up and left at some point before 10 AM. That, of course, means my first question will either not be asked at all or will be answered by one of the other doctors. And if Dr. Benson is not there, there is no point in asking my second question. Well, that was a missed opportunity.

Although most of the questions asked during the Sunday session do not relate to fibrinogen amyloidosis because many of them are questions about symptoms typically not associated with AFib or questions about the drugs for ATTR currently in clinical trials, I do enjoy the Sunday session anyway since I find most of the topics discussed very interesting and informative. It is also interesting to hear different doctors respond to the same question as they all have their unique perspective.

Then much to my surprise, about 20 minutes before the scheduled noon end time, Dr. Gertz must have gotten to the sheet of paper with both of my questions. I heard him read my second question first, somewhat quickly and quietly to himself, and he got a little chuckle out of it. Then he said something about the next question (referring to my Question 1) being for Dr. Benson but he has already gone. A couple of people then spoke up and said Dr. Benson was actually still there, and lo and behold he did make his way from the back of the room to a microphone stand in about the middle of the aisle.

Dr. Gertz asked Dr. Benson my first question about the signal peptide lengths, and he gave a long answer that went into some of the science behind what actually happens with the signal peptide. But he did eventually get around to the point that with TTR it's easy to do the math because you just add 20, whereas with something like fibrinogen "I have to get out my calculator because I have to add 19." I don't think he mentioned the lengths of any of the others, but I was glad he at least confirmed what I thought I knew about fibrinogen. Unfortunately Dr. Gertz did not ask Dr. Benson my second question at this point, which is too bad. He was probably trying to get a few more questions answered since he was running out of time.

Since the subject of nomenclature and this numbering scheme can lead to some confusion due to the different ways a genetic mutation can be written (I have seen the most common AFib mutation written at least three different ways in published medical journal articles), I will go over that in a separate post.

Around noon the meeting ended and we all had lunch, which included cookies for dessert because Dr. Benson had asked Muriel Finkel specifically for that. Cathy and I then said our goodbyes to Cathy T. and Lon before heading to the airport to catch our flight back home. We had a few hours before our flight, so I took Cathy on the full tour of O'Hare Airport since she had never been there before. If you ever have time to walk around inside O'Hare Airport in Chicago, do it. Much of it is just like any other airport, but there are a few interesting things to see.

That wraps up the 2017 Hereditary Amyloidosis meeting in Chicago. There was an evaluation sheet we completed after the meeting, and one of the questions asked where we would like to see the next meeting held in 2019. The choices were Chicago, Phoenix, Baltimore, Jacksonville, and Salt Lake City. I will be surprised if Muriel has it some place other than Chicago, but I suppose she is open to the idea since she asked the question. I plan on being there, wherever it is.

Saturday, November 11, 2017

2017 Hereditary Amyloidosis meeting - Saturday

Hello again, loyal blog readers. Are you shocked to see two posts in two days? I decided to publish my blog posts about the Chicago meeting over the course of three days, just like the meeting. So it is sort of like live-blogging, but two weeks after the event.

After breakfast Saturday morning (October 28) I headed to the Grand Ballroom for the meeting. I arrived about 40 minutes before the scheduled start time of 8:00 AM, and here is what the meeting room looked like from the back of the room:

As you can see, it was almost wall-to-wall chairs. I don't think the rows went that far back for the 2015 meeting. Not counting the partial rows of chairs where that screen was set up on the left side, I counted 18 rows of 22 chairs this time, which is 396. Add to that at least six rows of 11 chairs where the screen was, and now we're up to at least 462 chairs. That's a lot of chairs, and as you can see from a picture I took later in the day, they were needed.

I was also able to get some pictures of the dais at the front of the room before any of the doctors arrived.

(Note: As of the writing of this blog post the presentations from the meeting have not been posted online. If and when they are made available, I will update this post and also mention it in the next new blog post.)

After the introductory remarks by Muriel Finkel and Dr. Gertz, Dr. Benson gave the first presentation of the meeting. His topic was nomenclature, which is an appropriate topic for him to discuss because he is on the amyloidosis nomenclature committee. In my December 31, 2016 blog post I mentioned some changes recommended by the nomenclature committee in 2016. One of those was to use the term hereditary amyloidosis to refer to amyloidosis due to a mutation in the fibril protein itself, which is the case in fibrinogen amyloidosis. Dr. Benson did not discuss that in his presentation, but he did discuss the recommended change (which I don't see in the article I linked to in the December 31, 2016 blog post) in the numbering scheme for hereditary amyloidosis mutations.

The number typically used in the designation of a mutation is referring to the position of the change in the mature protein. But Dr. Benson explained that when a protein is initially created, there is a short section of it called the signal peptide that gets removed as the protein leaves the cell to go into the body and do its job. Dr. Benson only discussed the TTR protein, in which the signal peptide has a length of 20 amino acids. So the number used when referring to a position in the complete TTR protein (with the signal peptide) would be 20 more than the number used when referring to the mature protein (without the signal peptide). He didn't discuss the other amyloid proteins such as fibrinogen, lysozyme, etc., so keep that in mind for the next blog post.

The next presentation covered TTR amyloidosis (both mutant and wild type), and then the one after that was Dr. Berk's presentation on the non-ATTR varieties. Here are the notes I took during the fibrinogen portion of his presentation:

 - The annual decline in GFR for AFib patients is approximately 11.2. (In the past I had heard that 15 was the estimated annual decline.)

 - Biopsy slides of kidneys impacted by AFib show clear glomerular involvement. (We have seen that in medical journal articles I reviewed previously in the blog.)

 - One of the slides presented the data on transplant outcomes for AFib from one of the articles by the NAC in London. This was probably the 2009 article I reviewed in the January 12, 2014 blog post, so no real surprises there. The main takeaway from that data is a kidney transplant by itself will likely result in the transplanted kidney developing amyloidosis almost certainly within ten years, sometimes within a year or two. A combined liver-kidney transplant yields better results, but there are increased risks associated with that option.

 - Dr. Berk also mentioned that there was one patient (not part of the NAC study) who had received a liver-only transplant for AFib before going on dialysis, and was still alive seven years post-transplant. (He did not mention that the patient was sitting next to me at the time.)

There was a question and answer session after Dr. Berk's presentation, and Cathy T. asked how the US experience with organ transplants compares with the experience in the UK. The answer, unfortunately, is that nobody knows because the experience in the US is not consolidated anywhere. In the UK, all amyloidosis patients are referred to the NAC so it is much easier to collect information on all of the AFib patients there.

The next presenter was a genetic counselor from Mayo Clinic. I always enjoy these presentations because I get a little more out of each one and they always help me understand how others may feel about genetic testing. There were three items I made a note of during this presentation. First was the importance of having open communication among family members. The second was when the counselor talked about putting together a family letter to communicate to the potentially affected family members. If you go back to the entries in this blog from right after Mom was diagnosed with AFib, you'll find the family letter I put together to send to her cousins. The third item I made a note of was a recommendation from the counselor to identify the communicator in the family, which would be the person in the family with the most information about the disease and the ability to communicate with everyone who needs to be kept informed. I suppose I jumped right into that position when Mom was diagnosed.

Next was Dr. Picken, a pathologist who spoke about methods of diagnosing amyloidosis, and then Dr. Grogan, a  cardiologist from Mayo Clinic. A topic that generated some discussion in her presentation was a test called the PYP scan that is being used to diagnose amyloid involvement in the heart.

Next was Dr. Waddington-Cruz from Brazil with a presentation on neuropathy, followed by Dr. Clarke on gastrointestinal issues and Dr. Dispenzieri on solid organ transplants. Very little if any from those presentations was applicable to AFib.

Then it was time for lunch. That was a very full morning, wasn't it?

After lunch there were presentations by four different pharmaceutical companies on the status of some of the clinical trials underway for drugs intended to help ATTR patients. The good news is that there is some real progress being made in that area. The bad news is that none of these drugs currently in clinical trials will benefit AFib patients since they are intended to prevent or dissolve the buildup of TTR amyloid fibrils. The next presenter was Dr. Berk again who discussed a few other treatments that were not in clinical trials. Regarding doxycycline, which Boston University did study in a clinical trial, he said they did not see much benefit and there were some adverse effects.

After those presentations we divided into five breakout sessions, where different rooms are set up to discuss different topics and attendees can go to the room or rooms of their choosing. Cathy, Lon and I went to the session titled "Genetic Issues and Non-ATTR variants." There was some good discussion of the issues surrounding genetic testing, especially with regard to children and young adults. We did not ask any questions about fibrinogen amyloidosis, but some of the other people with non-ATTR variants did ask some questions about those.

That concludes the meeting agenda for Saturday. We have already answered the first question posed at the end of the previous blog post. Yes, all of this year's attendees did fit in the Grand Ballroom. But what about the second question? Did my wife brave the cold and go back to downtown Chicago on Saturday? No she did not. I can't say that I blame her, either. It was cold.

Next up is the Sunday Question and Answer session.

Friday, November 10, 2017

2017 Hereditary Amyloidosis meeting - Friday

Greeting, loyal Fibrinogen Amyloidosis blog followers. The number of email subscribers increased by one last month (first time in quite awhile), so I'd like to extend a special welcome to our newest subscriber. (I can only see the number of subscribers, not the email addresses.) As a reminder to email subscribers, the formatting of emails is sometimes not as good as the formatting of the blog post. So if the email looks awful, check the blog.

As I mentioned in the previous post, at the end of October I traveled to Chicago to attend the hereditary amyloidosis support group meeting that occurs every two years. (Side note: The word "biannual" can mean occurring twice a year (semiannual), or occurring once every two years (biennial). Isn't English a great language?) This was my fourth time to attend this meeting, having attended in 2011 and 2013 with Mom, and by myself in 2015. This year my wife Cathy was able to travel with me, so we decided to travel to Chicago Thursday evening and visit downtown Chicago together on Friday, and then Cathy would do her own thing on Saturday and Sunday while I attended the meeting. I'll blog about the meeting over three posts, with this first post covering the Friday before the meeting including the Meet-and-Greet Friday night.

When we flew in Thursday night the temperature was in the 50s, but we knew from the weather forecast that we wouldn't see 50 degrees again that weekend in Chicago. The weather forecast was indeed accurate. Friday morning we took the train from O'Hare airport to downtown Chicago and walked a few blocks to the Willis Tower (formerly Sears Tower) to go to the observation deck (Skydeck) on the 103rd floor. Here is the obligatory picture of our feet while we were standing on the Ledge, which is a series of four glass boxes that extend just over four feet outside the building, 103 floors up.

After visiting the Skydeck we took a Hop On-Hop Off bus to Millennium Park where we walked around looking at the various art installations. Here is the obligatory picture of our reflection in The Bean (Cloud Gate). I'm wearing a gray hat.

It was definitely cold while we were walking around Millennium Park, but we survived. We then made our way a few blocks north to have lunch before the 2 PM boat tour we had reservations for. We managed to stay on the upper deck for most of the boat tour so we could see the buildings along the Chicago River. (It was an architectural tour, after all.) But once the boat went out on Lake Michigan and started going a little faster we decided to go down below to an enclosed area with windows and have some hot chocolate. It was only then that I realized how cold my hands really were. I haven't been that cold in a very long time.

After the boat tour we walked around a bit, got on the Hop on-Hop off bus again to go through a little more of downtown Chicago, and then we got off close to a subway station to catch the train back to the airport.

After not having the traditional Friday evening Meet-and-Greet in 2015, it was back for the 2017 meeting. We found Cathy T. and her husband Lon, and it was good to catch up with them. Cathy's doing well 7 years after her liver transplant for fibrinogen amyloidosis. Just before we left we spoke with Dr. Benson for awhile. He was not aware of anything new with regard to fibrinogen amyloidosis, unfortunately. One of the topics discussed was liver-only transplants for fibrinogen amyloidosis patients, which he is still in favor of despite the reluctance of the doctors at the NAC in London to embrace it. He was not aware of any other liver-only transplants for AFib besides Cathy's.

That concludes the Friday before the actual start of the meeting. Tomorrow we'll answer two important questions:

1. Will all of this year's participants fit in the Grand Ballroom at the O'Hare Hilton? It seemed almost full in 2015, and this year's attendance is probably 30 to 40% more.

2. Will Cathy (my wife) brave the cold on Saturday and go back to downtown Chicago as planned?

Stay tuned . . .

=====Monthly Blog Status Update=====

As of September 30, 2017:

Total posts: 177 (1 in September)

Total pageviews: 72,700 (~1100 in September)

Email subscribers: 14 (unchanged)

Total number of countries that have viewed the blog: 142

No new countries viewed the blog in September:

=====Monthly Blog Status Update=====

As of October 31, 2017:

Total posts: 177 (0 in October)

Total pageviews: 73,800 (~1000 in October)

Email subscribers: 15 (increased by 1)

Total number of countries that have viewed the blog: 144

Two new countries viewed the blog in October: