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Following the death of Takara Hime, and the war on the Korean peninsula, Naka no Ōe was taking hold--or perhaps keeping hold--of the reins of government.  He wasn't finished with his changes to the government.  He also had a new threat--the Tang Empire.  They had destroyed Yamato's ally, Baekje, and defeated the Yamato forces on the peninsula.  While the Tang then turned their attention to Goguryeo, Yamato could easily be next.  The Tang had a foothold on the Korean peninsula, so they had a place to gather and launch a fleet, should they wish to bring Yamato into their empire. For more, especially to follow along with some of the names in this episode, check out our blogpost at https://sengokudaimyo.com/podcast/episode-125     Rough Transcript Welcome to Sengoku Daimyo's Chronicles of Japan.  My name is Joshua and this is episode 125: The Sovereign of Heavenly Wisdom The people of Baekje looked around at the strange and unfamiliar land.  They had fled a wartorn country, and they were happy to be alive, but refugee status was hardly a walk in the park.  Fortunately, they still knew how to farm the land, even if their homeland was hundreds of miles away, across the sea, and occupied by hostile forces.  Here, at least, was a land where they could make a home for themselves. Some of them had to wonder whether this was really permanent.  Was their situation just temporary until their kingdom was restored?  Or were they truly the last people of Baekje, and what would that mean? Either way, it would mean nothing if they didn't work the land and provide for their families.  And so, as with displaced people everywhere, they made the best of the situation.  They had been given land to work, and that was more than they could have asked for.  They might never return to Baekje, but perhaps they could keep a little of it alive for themselves and their descendants. Greetings, everyone, and welcome back.  Last episode we talked about the downfall of Baekje and the defeat of the Yamato forces at the battle of Hakusukinoe, also known as the Battle of Baekgang, in 663.  And yet, something else happened as well: the sovereign, Takara Hime, aka Saimei Tennou, died as the Yamato forces were setting out.  Immediately Prince Naka no Oe took the reins of government.  He would be known to later generations as Tenji Tennou, with Tenji meaning something like “Heavenly Wisdom”. Now Prince Naka no Oe has been in the forefront of many of our episodes so far, so I'd like to start this episode out with a recap of what we've heard about him so far, as all of this is important to remind ourselves of the complex political situation.  I'm going to be dropping – and recapping – a lot of names, but I'll have many of the key individuals listed on the podcast website for folks who want to follow along.  I would note that this episode is going to be a summary, with some extrapolation by me regarding what was actually happening.  Just remember that history, as we've seen time and again, is often more messy and chaotic than we like, and people are more complex than just being purely good or evil.  People rarely make their way to the top of any social hierarchy purely through their good deeds.  To start with, let's go back to before the year 645, when Naka no Oe instigated a coup against Soga no Iruka and Soga no Emishi.  In the Isshi Incident, covered in Episode 106, Naka no Oe had Soga no Iruka murdered in court, in front of his mother, Takara Hime, when she sat on the throne the first time.  And yet, though he could have taken the throne when she abdicated in apparent shock, he didn't.  Instead, he took the role of “Crown Prince”, but this wasn't him just sitting back.  In fact, evidence suggests that he used that position to keep a strong hand on the tiller of the ship of state. Prior to the Isshi Incident of 645, the rule of the Yamato sovereign had been eroded by noble court families.  These families, originally set up to serve the court and its administration, had come to dominate the political structures of the court.  The main branch of the Soga family, in particular, had found its way to power through a series of astute political marriages and the support of a new, foreign religion:  Buddhism.  Soga no Iname, Emishi's grandfather, had married his daughters to the sovereigns, and thus created closer ties between the Soga and the royal line.  He also helped ensure that the offspring of those marriages would be the ones to take over as future sovereigns.  Soga no Iname, himself took the position of Oho-omi, the Great Omi, or the Great Minister, the head of the other ministerial families.  As Prime Minister, he held great sway over the day-to-day running of the court, and execution of much of the administration.  Much of this was covered in previous episodes, but especially episodes 88, 90, 91, 92, 95, 98, 99, and 103. Soga no Umako, who succeeded his father as Oho-omi, was joined in his effort to administer the government by his grand-nephew, Prince Umayado, also known as Shotoku Taishi, son of Tachibana no Toyohi, aka Youmei Tennou, and thus grandson of Umako's sister, Kitashi-hime, and the sovereign known as Kimmei Tennou.  Umayado's aunt, sister to Tachibana no Toyohi, was Kashikiya Hime, or Suiko Tennou.  The three of them:  Soga no Umako, Prince Umayado, and Kashikiya Hime, together oversaw the development of Yamato and the spread of Buddhism.  Buddhism was also controversial at first, but they turned it into another source of ritual power for the state—ritual power that Soga no Umako, Prince Umayado, and even Kashikiya Hime were able to harvest for their own use. Unfortunately, the Crown Prince, Umayado, died before Kashikiya hime, suddenly leaving open the question of who would take the throne.  Soga no Umako himself, passed away two years before Kashikiya Hime.  When she in turn passed away, there was another struggle for the throne, this time between the descendants of Crown Prince Umayado and Soga no Umako.  Eventually, Soga no Umako's son and heir, Soga no Emishi, made sure that a more pliant sovereign, Prince Tamura, would take the throne, and Prince Umayado's own son, Prince Yamashiro no Oe, was cut out of the succession.  Soga no Emishi, serving as prime minister, effectively ran things much as his father had.  When Tamura diedhis queen, Takara Hime, took the throne, rather than passing it back to Umayado's line—no doubt with Emishi's blessing.  He was careful, however, not to provoke direct action against Yamashiro no Oe, possibly due to the reverence in which Yamashiro's father, Prince Umayado, aka the Buddhist Saint Shotoku Taishi, was held.  Meanwhile, Emishi appears to have been cultivating his grandson by way of Prince Tamura, Furubito no Oe, to eventually succeed to the throne, trying to duplicate what his own father Umako and even grandfather had been able to accomplish. Soga no Emishi's son, Soga no Iruka, was not quite so temperate, however.   Who would have thought that growing up at the top of the social hierarchy might make one feel a bit arrogant and entitled?   When Soga no Emishi was ill, Soga no Iruka took over as Prime Minister, and he didn't just stand back.  He decided that he needed to take out Furubito no Oe's competition, and so he went after Yamashiro no Oe and had him killed. Unfortunately for him, he apparently went too far.  There were already those who were not happy with the Soga family's close hold on power—or perhaps more appropriately, this particular line of the Soga family.  This kind of behavior allowed a group of discontented royals and nobility to gain support. According to the popular story recounted in the Nihon Shoki, the primary seed of resistance started with a game of kickball, or kemari.  Nakatomi no Kamako, aka Nakatomi no Kamatari, was the scion of his house, which was dedicated to the worship of the traditional kami of Yamato.  The Nakatomi were ritualists: in charge of chanting ritual prayers, or norito, during court ceremony.  This meant that their powerbase was directly challenged by the increasing role of Buddhism, one of the Soga patriarchs' key influences on the political system. Kamatari was feeling out the politics of the court, and seemed to be seeking the support of royal family members who could help challenge the powerful Soga ministers.  He found that support in two places.  First, in Prince Karu, brother to Takara Hime, the current sovereign, who had been on the throne ever since her husband, Tamura, had passed away.  And then there was the Prince Katsuraki, better known to us, today, as Prince Naka no Oe.  A game of kemari, where a group of players tried to keep a ball in the air as long as they could, using only their feet, was a chance to get close to the Prince.  When Naka no Oe's shoe flew off in the middle of the match, Kamatari ran over to retrieve it.  As he offered the shoe back to its owner, they got to talking, and one of the most impactful bromances in Yamato history was born. The two ended up studying together.  The unification of the Yellow River and Yangzi basin regions under the Sui and Tang, and the expansion of the Silk Road, had repercussions felt all the way across the straits in Yamato.  Naka no Oe and Kamatari were both avid students and were absorbing all that the continent had to throw at them about philosophy and good governance.  As is so often the case, it seems like idealistic students were the fertile ground for revolutionary new thoughts. There were problems implementing their vision, however.  Although the Nihon Shoki claims that Naka no Oe was the Crown Prince, that honor was probably given to Prince Furubito no Oe, who would have no doubt perpetuated the existing power structures at court.  This is something that the Chroniclers, or perhaps those before them, glossed over and may have even tried to retconned, to help bolster the case that Naka no Oe was actually working for the common good and not just involved in a naked power grab for himself.  There is also the question as to where Yamashiro no Oe had stood in the succession, as he likely had a fair number of supporters. With the destruction of Yamashiro no Oe's family, however, the balance of power shifted.  Although Soga no Emishi had long been an influential member of the court, and not solely because of his role as Prime Minister, Soga no Iruka was relatively new to power.  Yamashiro no Oe's family, in turn, likely had a fair number of supporters, and even neutral parties may have been turned off by Iruka's violent methods to suppress an opponent who had already been defeated politically.  Naka no Oe and Kamatari seem to have seized on this discontent againt the Soga, but they needed at least one other conspirator.  They achieved this by offering a marriage alliance with Soga no Kurayamada no Ishikawa no Maro, a lesser member of the Soga household, whose own immediate family had been supporters of Yamashiro no Oe, and so likely had plenty of grievances with his cousins.  Naka no Oe married Ishikawa no Maro's daughter, Wochi no Iratsume, also known as Chinu no Iratsume.  Together, these three—Naka no Oe, Kamatari, and Ishikawa no Maro—brought others into their plot, and finally, in 645, they struck.  Soga no Iruka was killed at court, in front of a shocked Takara Hime and Prince Furubito no Oe.  By the way, this is another thing that suggests to me that Furubito no Oe was the Crown Prince, because why was he front and center at the ceremony, while Naka no Oe was able to skulk around at the edges, tending to things like the guards?  After the assassination at the court – the Isshi Incident -- Naka no Oe gathered forces and went after Soga no Emishi, since they knew they couldn't leave him alive.  With both Soga no Emishi and Soga no Iruka dead, and Takara Hime having abdicated the throne in shock at what had just occurred, Naka no Oe could have taken the throne for himself.  However, in what was probably a rather astute move on his part, he chose not to.  He recognized that Furubito no Oe's claim to the throne was possibly stronger, and those who had supported the Soga would not doubt push for him to take the throne.  And so, instead, he pushed for his uncle, Prince Karu, to ascend as sovereign.  Karu was Takara Hime's brother, and they could use Confucian logic regarding deference to one's elders to support him.  Plus, Karu's hands weren't directly bloodied by the recent conflict. As for Prince Furubito, he saw the way that the winds were blowing.  To avoid being another casualty, he retired from the world, taking the vows of a Buddhist monk.  However, there were still supporters who were trying to put him on the throne and eventually he would be killed, to avoid being used as a rallying point. Prince Karu, known as Jomei Tennou, ruled for around a decade. During that time, Naka no Oe and his reformers helped to cultivate a new image of the state as a bureaucratic monarchy.  Naka no Oe was designated the Crown Prince, and Nakatomi no Kamatari was made the “Inner Prime Minister”, or Naidaijin.  Ishikawa no Maro was made the minister of the  Right, while Abe no Uchimaro was made Minister of the Left, and they ran much of the bureaucracy, but the Naidaijin was a role more directly attached to the royal household, and likely meant that Kamatari was outside of their jurisdiction, falling into a position directly supporting Naka no Oe.  They instituted Tang style rank systems, and set up divisions of the entire archipelago.  They appointed governors of the various countries, now seen as provinces, and made them report up to various ministers, and eventually the sovereign.  After all, if you were going to manage everything, you needed to first and foremost collect the data.  This period is known as the Taika, or Great Change, period, and the reforms are known as the Taika reforms, discussed in episode 108. They even built a large government complex in the form of the Toyosaki Palace, in Naniwa, though this may have been a bit much—for more, check out episodes 112 and 113. Years into the project, though, things seem to have soured, a bit.  Rumors and slander turned Kamatari against his ally, Ishikawa no Maro, resulting in the death of Ishikawa no Maro and much of his family.  Naka no Oe and other members of the royal family eventually abandoned the Naniwa palace complex, leaving now-Emperor Karu and the government officials there to run the day-to-day administration, while much of the court made its way back to the Asuka area.  Karu would later pass away, but the throne still did not pass to Crown Prince Naka no Oe, despite his title.  Instead, the throne went back to Takara Hime.  This was her second reign, and one of only two split reigns like this that we know of.  The Chroniclers, who were creating posthumous titles for the sovereigns, gave her two names—Kogyoku Tennou for her reign up to 645, and then Saimei Tennou for her second reign starting in 655.   During her latter reign, Naka no Oe continued to wield power as the Crown Prince, and the Chroniclers don't really get into why she came back into power.  It may be that Naka no Oe, in his role as Crown Prince, had more freedom: although the sovereign is purportedly the person in power, that position can also be limiting.  There are specific things which the sovereign is supposed to do, rituals in which they are expected to partake.  In addition, there were restrictions on who was allowed into the inner sanctum of the palace, and thus limits on who could interact with the sovereign, and how.  That meant that any sovereign was reliant on intermediaries to know what was going on in their state and to carry out their orders.  As Crown Prince, Naka no Oe may have had more flexibility to do the things he wanted to do, and he could always leverage the sovereign's authority. When Baekje was destroyed, and Yamato decided to go to their aid, Naka no Oe appears to have had a strong hand in raising forces and directing movements, at least within the archipelago.  When Takara Hime passed away rather suddenly, he accompanied her funerary procession much of the way back, and then returned to Tsukushi—Kyushu—to direct the war.   This is the same thing that Toyotomi Hideyoshi would do when he sent troops to Korea in the late 16th century.  Moving headquarters closer to the continent would reduce the time between messages.  Theoretically he could have moved out to the islands of Iki or Tsushima, but I suspect that there were more amenities at Tsukushi, where they even built a palace for Takara Hime—and later Naka no Oe—to reside in.  It was likely not quite as spectacular as the full-blown city that Hideyoshi developed in a matter of months, but the court could also leverage the facilities previously created for the Dazaifu. The war took time.  This wasn't like some “wars” that were more like specific military actions.  This was a war that dragged on for several years, with different waves of ships going over to transport people and supplies.  Things came to a head in the 9th month of 663, roughly October or November on the Western calendar.  The Baekje resistance was under siege, and their only hope was a fleet of Yamato soldiers coming to their aid.  The Yamato fleet met with a much smaller Tang fleet at the mouth of the Baek River—the Hakusukinoe.  They attempted to break through the Tang blockade, but the Tang had positional advantage and were eventually able to counterattack, destroying the Yamato fleet.  Without their relief, the Baekje resistance fell. The remnants of the Yamato army, along with those Baekje nobles that were with them, headed out, fleeing back to the archipelago.  One presumes that there may have been other Baekje nobles, and their families, who had already made the trip. After the entry describing this rout, on the 24th day of the 9th month of 663, we have a gap in the Chronicles of just a little more than 4 months.  We then pick up with Naka no Oe's government starting to look at internal affairs.  For one thing, we are told that he selected his younger brother, the Royal Prince Ohoama, as Crown Prince, and he made updates to the cap-rank system, changing it from 19 ranks to 26 ranks.  The first six ranks remained the same, but the name “kwa”, or “flower”, for the 7th through 10th ranks was changed to “Kin”, meaning “brocade”.  Furthermore, a “middle” rank was added between the Upper and Lower ranks, further distinguishing each group, and adding 6 extra ranks.  Finally, the initial rank, Risshin, was divided into two:  Daiken and Shouken.  We aren't told why, but it likely meant that they could have more granular distinctions in rank. At the same time that was going on, the court also awarded long swords to the senior members of the great families, and short swords to the senior members of lesser families.  Below that, senior members of the Tomo no Miyatsuko and others were given shields and bows and arrows.  Furthermore, the vassals, or kakibe, and the domestic retainers, or yakabe, were settled, to use Aston's translation.  The kanji used in the text appears to refer to settling a decision or standardizing something, rather than settling as in giving a place to live.  It seems to me to mean that the court was settling servants on families: determining what kind and how many servants that various houses could have based on their position in the hierarchy.  I can't help but notice that all of these gifts were very martial in nature.  That does not mean, of course, that they were necessarily because of the war over Baekje, nor that they were in response to the concern about a possible Tang invasion -- we've seen in the past where swords were gifted to people who had served the court --but it is hard not to connect these gifts with recent worries.  We also know that this year, Naka no Oe turned his focus on building defenses, setting up guards and beacon fires on the islands of Tsushima and Iki.   Should any unknown fleet be seen coming to the archipelago, the fires would alert the forces at Kyushu, so they could send word and prepare a defense. In addition, the court built an impressive defense for Tsukushi—for the Dazai itself, the seat of the Yamato government in Kyushu.  It is called the Mizuki, or Water Castle, though at the time “castle” was more about walls and fortifications than the standalone fortress we tend to think of, today.  Along those lines, the Mizuki was an earthen embankment, roughly 1.2 kilometers long, extending from a natural ridgeline to the west across the Mikasa river.  Archeological evidence shows it had a moat, and this line of fortifications would have been a line of defense for the Dazai, should anyone try to invade.  This construction was so large and impressive that you can still see it, even today.  It stands out on the terrain, and it is even visible from overhead photographs. In the third month of 664, we are told that Prince Syeongwang of Baekje and his people, were given a residence at Naniwa.  In fact, even though Baekje was no longer an independent kingdom, there appear to have been thousands of Baekje people now living in Yamato, unable to return home.  Many of these were former nobles of the Baekje court, which Yamato treated as a foreign extension of its own.  Resettling these people would be a major theme for the Chronicles, but we will also see, as we read further on, how their talents were leveraged for the state. Also in the third month, a star fell in the north—it says “in the north of the capital”, but I suspect that anywhere north, south, east, or west of the capital would have seen the same thing “in the north”.  There was also an earthquake, which isn't given any particular significance, beyond its mention as a natural phenomenon. On the 17th day of the 5th month of 664, so roughly 2 months later, we are told that Liu Jen'yuan, the Tang dynasty's general in Baekje, sent Guo Wucong  to Yamato with a letter and gifts.  We aren't told the contents of the letter, but one imagines that this may have been a rather tense exchange.  Yamato had just been involved in open warfare against Tang forces on the peninsula, and they still weren't sure if the Tang empire would come after them next.  Their only real hope on that front was Goguryeo, since the Tang and Silla were still trying to destroy the Goguryeo kingdom, and that may have kept the Tang forces tied up for a while.  No doubt Guo Wucong would have seen some of the defenses that Yamato was constructing during his visit. Guo Wucong would hang around for about seven and a half months.  He was given permission to take his leave on the 4th day of the 10th month.  Naka no Oe had his friend and Inner Prime Minister, Nakatomi no Kamatari send the Buddhist Priest, Chisho, with presents for Guo Wucong, and he and his officers were granted entertainments  before they left as well. Finally, Guo Wucong and his people returned to the Tang on the 12th day of the 12th month. While the delegation from the Tang was in Yamato, we are told of several tragedies.  First was that Soga no Murajiko no Oho-omi had passed away.  Soga no Murajiko appears to have been another son of Soga no Kuramaro, and thus brother to Soga no Ishikawa no Maro.  Unfortunately, we don't have much more on him in the record. Just a month later, we are told that the “Dowager Queen” Shima passed away.  Aston translates this as the Queen Grandmother, suggesting that she was Naka no Oe's grandmother. We are also told, that in the 10th month of 664, around the time that Guo Wucong was given leave to depart, that Yeon Gaesomun, the Prime Minister—though perhaps more correctly the despotic ruler—of Goguryeo, died.  It is said that he asked his children to remain united, but, well, even if we didn't know how it all turned out, I think we would look somewhat skeptically on any idea that they all did exactly as they were told.  Sure enough, in 667 we are told that Gaesomun's eldest son, Namseng, left the capital city of Pyongyang to tour the provinces, and while he was gone his younger brothers conspired with the nobility, and when he came back they refused to let him back in.  So Namseng ran off to the Tang court and apparently helped them destroy his own country. This is largely corroborated by other stories about Goguryeo, though the dates do seem to be off.  Tang records put Gaesomun's death around 666 CE, which the Samguk Sagi appears to follow, but on his tomb the date would appear to be 665.  Confusion like this was easy enough given the different dates and trying to cross-check across different regnal eras.  Sure, there were some commonalities, but it was very easy to miscount something. One last note from the twelfth month of 664—it seems that there were omens of apparent prosperity that came to the court from the island of Awaji.    First, there was rice that grew up in a farmer's pig trough.  The farmer's name is given as Shinuta no Fumibito no Mu, and Mu gathered this rice and stored it up, and thus, every day his wealth increased.  Then there was the bridal bed of Iwaki no Sukuri no Oho, of Kurimoto district.  They claimed that rice grew up at the head of his brides' mattress during her first night's stay with him.  And this wasn't just some brand new shoot, but overnight it formed an ear, and by the morning it bent down and ripened.  Then, the following night, another ear was formed.  When the bride went out into the courtyard, two keys fell down from heaven, and after she gave them to her husband, Oho, he went on to become a wealthy man. The exact purpose of these stories is unclear, but it seems to be that the Chroniclers are choosing to focus on stories of wealth and growth, which speak to how they wanted this reign as a whole, including the sovereign, to be remembered. However, more tragedy struck the following year, in 665,  when Hashibito, another Dowager Queen – this time the wife of Karu, aka Koutoku Tennou - passed away on the 25th day of the 2nd month.  On the first day of the 3rd month, 330 people took Buddhist vows for her sake. We are also told that in the second month the ranks of Baekje were cross-referenced with the ranks of Yamato, and then ranks were given out to some of the Baekje nobles that had come over to Yamato.  Kwisil Chipsa, who was originally ranked “Dalsol” in Baekje, was accorded “Lower Shoukin”.  That was rank 12 of the 26.  In comparison, “Dalsol” seems to have been the 2nd rank of 16 in Baekje.  Along with handing out rank, over 400 Baekje commoners, both men and women, were given residence in the Kanzaki district in Afumi.  This appears to be an area along the Aichi river, running from the Suzuka Mountains, west towards Lake Biwa. The court granted them rice-lands in the following month.  At the same time, several high ranking Baekje nobles were put in charge of building castles at strategic points around the archipelago.  These included one castle in Nagato, as well as the castles of Ohono and Woyogi, in Tsukushi.  Two years later, in 667, we also see the building of Takayasu castle, in Yamato and Yashima castle in Yamada, in Sanuki—modern Kagawa, on Shikoku, facing the Seto Inland Sea passageway.  Kaneda castle in Tsushima was also a Baekje-built one. We mentioned something about these castles last episode.  They were in the Baekje style, and as I said, the term “castle” here is more about the walls, which were largely made of rammed earth ramparts.  This means that you pile up earth and dirt in a layer and then the laborers use tools specifically to tamp it down until it is thick and hard.  Then another layer is piled on top and the process is repeated.  These walls were often placed on mountain tops, and they would follow the terrain, making them places that were easy to defend.  Beyond that, they didn't necessarily have a donjon keep or anything like that—maybe a tower so that one could see a little further, but being at the top of a mountain usually provided all the visual cues that one needed. We know there were other castles made as well.  For example, I mentioned last week about Kinojo, in Okayama, the ancient Kibi area.  Kinojo is not mentioned in the Nihon Shoki, but it clearly existed back then, and matches the general description of a 7th century mountain castle as built in Baekje.  The name means Demon Castle, and there is a story about it that is connected to the local Kibitsu Jinja—the Shrine to Prince Kibi.  According to legend, Kibitsu Hiko, aka Prince Kibitsu or, perhaps more appropriately, the Prince of Kibi, came to the area around the time of the Mimaki Iribiko, so probably about the 3rd century, at the head of a large force.  Kibitsu Hiko had come to defeat the demon, Ura, who lived in the nearby castle, hence Kinojo, and legend says that he freed the people from the demon's rule. As I also mentioned, last week, this particular castle may have ended up in the Momotaro story.  There are those who believe that the story of Momotarou is based on the story of Prince Kibitsu Hiko, and his defeat of the so-called demon, “Ura”.   Certainly the story has grown more fantastical, and less connected to the ancient history of the Kibi region, but it still may have its origin in a much more standard legend of a founding prince of the ancient Kibi kingdom that was later changed into a fairy tale.   More likely, the castle was built by a Baekje nobleman, often thought to be a prince, who settled in the area.  There is the possibility that the demon's name “Ura” came from a mistranslation of his name, or it is also possible that he was unrelated to the story at all.  The Kibitsu Hiko legend may have incorporated the castle, Kinojo, at a later date, once people had forgotten when and why the castle was actually built. It would make sense if Kinojo had been built as part of the defenses for Yamato, as that area overlooks a large part of the fertile plains of Okayama and out beyond Kojima to the Seto Inland Sea -- it is perched over a key overland route from the western edge of Honshu to Yamato, and there would have been several ways to signal boats to put to sea to intercept forces on the water.  . This all suggests to me that Kinojo was probably part of Naka no Oe's castle-building effort, even if it isn't specifically remembered in the Chronicle.  But building castles wasn't enough to bring peace of mind that Yamato would survive a Tang invasion, and it is possibly as a defensive measure that Naka no Oe would go on to do something truly incredible—he would eventually move the capital from Asuka and Naniwa all the way to the shores of Lake Biwa itself, establishing the Ohotsu palace.  This was a truly extreme step that didn't endear Naka no Oe to the court, but it had several advantages.  For one thing, this move pulled the capital further away from the sea routes, meaning that if they were attacked, they had a more defensible position.  Even more so than Yamato, the Afumi region around Lake Biwa is surrounded by mountains, with a few narrow passes that restricted movement in and out. One of these is the famous Sekigahara, which remained a choke point even up to modern times.  The name even means the Field of the Barrier, indicating the barrier and checkpoint that had been set up there in ancient times.  Moving the capital also pulled the court away from some of the previous political centers, which may have been another feature that made it attractive to Naka no Oe.  Many capital moves have been made, at least in part, to get farther away from strong Buddhist temples, and this certainly would have moved things out of the Asuka region, which by now was a hotbed of Buddhist temple activity. But we'll talk about that all more, next episode.  Until then, thank you once again for listening and for all of your support. If you like what we are doing, please tell your friends and feel free to rate us wherever you listen to podcasts.  If you feel the need to do more, and want to help us keep this going, we have information about how you can donate on Patreon or through our KoFi site, ko-fi.com/sengokudaimyo, or find the links over at our main website,  SengokuDaimyo.com/Podcast, where we will have some more discussion on topics from this episode. Also, feel free to reach out to our Sengoku Daimyo Facebook page.  You can also email us at the.sengoku.daimyo@gmail.com.  Thank you, also, to Ellen for their work editing the podcast. And that's all for now.  Thank you again, and I'll see you next episode on Sengoku Daimyo's Chronicles of Japan

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Lets Learn Sumo - Day 13 & 14 of the Osaka Grand Sumo Tournament, Haru Basho. A Grandstand finish is set for Day 15.Send us a text

Let's Learn Sumo - Day 12 Grand Sumo Tournament, Haru Basho, Osaka Japan. The  leading pack see saws day to day!Send us a text

A few exciting moments from days 4 - 10 including Ura's flair, chinks in Onosato's armor, Hoshoryu's elbow, Ichiyamamoto's very good day, and Takayasu's dream. More about Sumo Kaboom and our BINGO game sponsored by bigsumofan.com: www.sumokaboom.com Bigsumofan.com is an online sumo merch store based in US, and they ship to over 30 countries. www.bigsumofan.com Twitter @SumoKaboom Instagram https://www.instagram.com/sumokaboom/ Facebook https://www.facebook.com/SumoKaboom/ YouTube https://www.youtube.com/c/SumoKaboomPodcast Check out our Sumo Kaboom tshirts and sweatshirts at Bonfire. (https://www.bonfire.com/store/sumo-kaboom/) Ever wonder where we get our research? Check out the Show Notes section of our website. Please follow or send us a review. It all helps! Thank you so much!

Let's Learn Sumo - Day 11 Grand Sumo Tournament Haru Basho, Osaka, Japan. A quick update on Day 11 matches - we have a race for the Yusho. Send us a text

Lets Learn Sumo - Days 9 & 10, Grand Sumo Tournament in Osaka, Japan. We have a sole leader. Send us a text

In this episode of Living a Nutritious Life, we're thrilled to welcome Dr. Katie Takayasu, a leading integrative medicine physician known for her tailored approach to treating digestive issues and women's health in midlife.What You'll Learn in This Episode:Gain insights into what constitutes a healthy digestive process and the importance of addressing bowel function as a "non-event."Discover the five critical factors impacting metabolism and digestion, including food quality, timing of meals, and the nervous system.Understand the significance of a robust microbiome in gut health, especially during hormonal fluctuations in midlife.Learn about heart health essentials, including the interpretation of cholesterol numbers, HRV, and integrative approaches to cardiovascular wellness.Episode Highlights:[00:01:07] Dr. Katie describes the characteristics of a healthy digestive process, focusing on regular bowel movements.[00:04:48] Discussion on the role of food quality, meal timing, and the microbiome in digestive health.[00:26:39] Exploring gut health in midlife and its connection to hormonal changes during perimenopause.[00:34:06] In-depth conversation on heart health and understanding cholesterol metrics, including the role of HRV in stress management.Welcome to the Living a Nutritious Life podcast with Keri Glassman, MS, RDN, CDN, where we break down the latest nutrition science into smart, actionable tips to help you live your most nutritious life.On the Living a Nutritious Life podcast, Keri and her world-renowned guests cut through the noise, sharing unparalleled, forward-thinking tips, tricks, and the latest in health, wellness, and nutrition science.Based on Keri's whole-person approach to healthy living, each impactful episode extends far beyond the simplistic “get more sleep” and “eat your greens” advice. She connects the dots like no one else – like how morning yoga can make it easier to choose a healthy lunch, leading to better sleep at night.Listen as Keri and her expert guests explore the physiological and behavioral connections that explain, for example, why the common wisdom around dieting and exercising alone doesn't work, so you can finally make the meaningful changes you've been looking for.Thank you for listening in to this episode of Living a Nutritious Life. We hope you enjoyed the conversation as much as we did! If you found value in this episode, please RATE, REVIEW and SHARE.Are you ready to dive into the world of nutrition and wellness even deeper and become a certified nutrition coach? Join our amazing global community of like-minded students and alumni. Get in on the action—enroll in our Become a Nutrition Coach program at nutritiouslife.com/bnc.Follow Dr. Katie for more insights into integrative medicine and holistic health practices.IG: @DoctorKatieLinks Mentioned in the Episode:Heartmath Meditation: https://www.heartmath.com/Dr. Katie's Cookbook: Plants First: A Physician's Guide to Wellness Through a Plant-Forward DietConnect with Keri on social:Instagram: https://www.instagram.com/nutritiouslifeofficial/Instagram: https://www.instagram.com/keriglassman/ Hosted on Acast. See acast.com/privacy for more information.

ACR 24: What I learned in Sjogren's, Takayasu's and CAR-T:Dr. Janet Pope Anti IL-17 on Entheseal Biopsy in PsA:Dr. Eric Dein  axSpA: Impact of TNF and IL-17 in Patients with Prior TNF Exposure:Dr. Brian Jaros Can We Make Clinical Trials Better?:Dr. Janet Pope Cumulative Steroid Use and Cardiovascular Events:Dr. Mrinalini Dey  IL 6 Inhibitors, Frailty and Polymyalgia Rheumatica:Drs. Trish Harkins and Sebastian Sattui IVIG Treatment in Immune-mediated Necrotizing Myopathy:Drs. Caoilfhionn Connolly interviews Dr. Asim Mohamed  Machine Learning for Predicting Flares in axSpA:Dr. Sheila Reyes So really, are JAKs Safe?:Dr. Janet Pope Tackling the Workforce Crisis: A shared dilemma:Drs. Mrinalini Dey,  Louise Pollard and Bharat Kumar The 2024 ACR Guidelines for Lupus Nephritis:Dr. Sheila Reyes  The Real Value of JAKi is Beyond RA:Dr. David Liew  Vaccine Responses:The DMARD Counts:Dr. David Liew

(Actualidad Médica 31) Recomendaciones para el manejo de arteritis de células gigantes y de Takayasu - Parte 2Continuamos hoy con las recomendaciones de manejo del colegio americano de reumatología y la vasculitis foundation para arteritis de células gigantes y arteritis de Takayasu. En este podcast nos centraremos en el manejo de la arteritis de células gigantes, es fundamental que tengamos en cuenta las definiciones revisadas en podcast previo, así que si no lo han escuchado les recomiendo hacerlo antes.ENLACE AL ARTÍCULO https://bit.ly/actualidadmédica30Te invitamos a que participes en la sección de comentarios.¿Qué quieres escuchar? ¿Cuáles son tus temas de interés?Síguenos en www.reumatimes.com, donde podrás encontrar cubrimientos de congresos de reumatología y resúmenes de actualidad en la especialidad. Encuéntranos en YouTube como ReumaTimes Y Facebook como Reumatologia.Online o ReumaTimes, en Instagram como dr.sebastianherrera o ReumaTimes, y en X (antes Twitter) como @Reuma_Online_ o @ReumaTimes. Estamos también en TikTok como @Reuma_Times.Síguenos en www.reumatimes.comTambién puedes encontrarnos en: Twitter: https://twitter.com/Reuma_Online_ Facebook: https://www.facebook.com/reumatologiaonline/ Instagram: https://www.instagram.com/dr.sebastianherrera/ Spreaker: https://www.spreaker.com/user/11390404 Spotify: https://spoti.fi/3DILwLP

(Actualidad Médica 30) Buen día, hoy otro podcast de Actualidad Médica.   Hoy vamos a explorar dos enfermedades reumatológicas complejas que afectan los vasos sanguíneos: la arteritis de células gigantes (ACG) y la arteritis de Takayasu (AT). Estas enfermedades, aunque poco comunes, pueden tener un impacto significativo en la vida de quienes las padecen.ENLACE: https://bit.ly/actualidadmédica30Te invitamos a que participes en la sección de comentarios.¿Qué quieres escuchar? ¿Cuáles son tus temas de interés?Síguenos en www.reumatimes.com, donde podrás encontrar cubrimientos de congresos de reumatología y resúmenes de actualidad en la especialidad. Encuéntranos en YouTube como ReumaTimes Y Facebook como Reumatologia.Online o ReumaTimes, en Instagram como dr.sebastianherrera o ReumaTimes, y en X (antes Twitter) como @Reuma_Online_ o @ReumaTimes. Estamos también en TikTok como @Reuma_Times.Síguenos en www.reumatimes.comTambién puedes encontrarnos en: Twitter: https://twitter.com/Reuma_Online_ Facebook: https://www.facebook.com/reumatologiaonline/ Instagram: https://www.instagram.com/dr.sebastianherrera/ Spreaker: https://www.spreaker.com/user/11390404 Spotify: https://spoti.fi/3DILwLP

Sumo: Ozeki Kotozakura Falls to 7-3 with Loss to Takayasu at Summer Tournament

Sumo: Former Ozeki Takayasu Withdraws from Summer Tournament with Back Pain

Dr. Katie Takayasu is an Integrative Medicine physician, author, and speaker in the holistic health space, bridging the gap between traditional Western medicine and the evidenced-based complementary health tools of nutrition, acupuncture, meditation, botanicals and lifestyle optimization. She is an Assistant Professor of Clinical Medicine at Columbia University/New York Presbyterian and teaches the next generation of doctors about healing the whole patient mind, body and spirit. Joe Donahue spoke with her at a CulinaryArts@SPAC event on March 25, 2023. Dr. Katie Takayasu's book is “Plants First: A Physician's Guide to Wellness Through a Plant-Forward Diet.”

CardioNerds join Dr. Tony Li Yi Wei, Dr. Rodney Soh Yu Hang, and Dr. Zan Ng Zhe Yan from the National University Heart Centre Singapore for a cocktail drink on the top of marina bay sands. They discuss the following case featuring a young woman with recurrent ACS ultimately found to have Takayasu Arteritis. The ECPR for this episode is provided by Dr. Teng Gim Gee and Professor Tan Huay Cheem. Episode audio was edited by student Dr. Shivani Reddy. A 37-year-old woman presents with chest pain. She has a background history of Hashimoto thyroiditis, gestational diabetes, and anemia of chronic disease and possible iron deficiency. Her significant medical history includes ischemic heart disease with prior coronary angiogram showing triple vessel coronary artery disease for which she underwent coronary artery bypass graft surgery (CABG) with LIMA-LAD, SVG-OM, SVG-RCA. After CABG, she had recurrent admissions in the subsequent year with acute coronary syndromes where she underwent percutaneous coronary intervention (PCI) to SVG-OM, RI, proximal LAD, and distal LAD. She was a non-smoker and had been compliant with her medications. For her current presentation, she underwent myocardial perfusion imaging which showed a large sized area of inducible ischemia in the LCx territory.  Repeat coronary evaluation showed occluded SVG-OM, occluded LIMA-LAD where she underwent PCI. Clinically, she was noted to have weak brachial and radial pulses on the left side with systolic blood pressure difference between both arms. CT Thoracic Angiogram demonstrated concern for underlying large vessel vasculitis such as Takayasu arteritis. ESR was elevated at 34. Rheumatology was consulted and she was diagnosed with Takayasu arteritis and started on prednisolone and azathioprine. Given her young age, absence of traditional atherosclerotic risk factors, and progressive coronary disease, Takayasu arteritis was deemed the underlying etiology of her coronary disease. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - Recurrent ACS Pearls - Recurrent ACS Approach to accelerated CAD and/or CAD in the young: Causes of MI in young patients can be divided into four groups, although a considerable overlap exists between all groups. (1) atheromatous CAD, (2) non-atheromatous process such as spontaneous coronary artery dissection, vasculitides such as Takayasu disease, (3) hypercoagulable states leading to recurrent arterial and venous thrombosis and/or thromboembolism, and (4) recreational drug use. Clinical Presentation of Takayasu and prevalence of cardiac involvement: Takayasu's arteritis is classified as a large-vessel vasculitis because it primarily affects the aorta and its primary branches. It has a worldwide distribution; however, the greatest prevalence is seen in Asia. Women are affected in 80 to 90 percent of cases, with an age of onset that is usually between 10 and 40 years. Management of Takayasu arteritis: As for systemic anti-inflammatory therapy, the mainstay of treatment would be systemic glucocorticoids guided by the care of a rheumatologist. A steroid sparing agent may be given in conjunction for long term suppressive therapy to achieve longer-term disease control. The choice of additional agents depends on several factors including considerations regarding comorbidities, a patient's plans for conceiving a child, cost of treatments, and availability of specific agents. Options include methotrexate, azathioprine as well as mycophenolate. There are also growing studies into anti-TNF-alpha agents such as etanercept or infliximab. Show Notes - Recurrent ACS

Looks like Takayasu is making another run for the yusho! Will Atamifuji dash his dreams once again? Will our new ozeki get remember how to do good sumo? Will anyone read our sumo smut?? Grab some sweet sumo merch: https://www.redbubble.com/people/SumoPunx/ or https://www.teepublic.com/user/sumo-punx  Or toss some coin into our tip bucket: https://ko-fi.com/sumopunx Find Sumo Punx podcast episodes... Spotify: https://open.spotify.com/show/0TZO9Bszi3voDkVwO9jhDf?si=a691ab22d5ed49b2 Apple Podcasts: https://podcasts.apple.com/us/podcast/sumo-punx/id1615858347 Google Podcasts: https://podcasts.google.com/feed/aHR0cHM6Ly9hbmNob3IuZm0vcy84MjIxNzQyNC9wb2RjYXN0L3Jzcw YouTube: https://www.youtube.com/@sumopunx Come say hello... Twitter: https://twitter.com/PunxSumo Instagram: https://www.instagram.com/sumopunx/ Facebook: https://m.facebook.com/SumoPunx/ Email us at sumopunx@gmail.com --- Support this podcast: https://podcasters.spotify.com/pod/show/sumo-punx/support

We discuss the general differential diagnosis & framework of workup for large-vessel, medium-vessel & small-vessel vasculitides, general treatment guidelines and prognostication for vasculitides; Then we focus (in this episode) on large-vessel vasculitides (Giant-cell & Takayasu arthritis)

Meet Lucy! After fighting for anyone to take her seriously, because she was "too young" to be sick, Lucy had to learn how to manage life with Takaysau's Arteritis, being a young mom, and advocating for herself. Now, she uses one of her strongest tools - nutrition - to help others live healthier lives. Read her blog post on the Anti-Inflammatory Diet here Follow Lucy: Instagram @_heal_thy_self__ Facebook at Heal THY self Nutrition Email: lucy@healyselfnutrition.ca Please don't forget to click that subscibe button whereever you listen to the podcast and do me a HUGE favor and leave a review! These two things help others find the podcast, find our community, and feel a little less alone in their journey through life with chronic illness! Join us on Instagram: https://www.instagram.com/teamvasculitis Join the Email List: https://teamvasculitis.com/team-vasculitis-email

Acometimento cardiovascular da arterite de takayasu by Cardiopapers

4.03 Large Vessel Vasculitis Rheumatology review for the USMLE Step 1 Exam Vasculitis is inflammation of blood vessels Vasculitis is split into three groups based on the size of blood vessels affected: large, medium, and small vessel vasculitis Large vessel vasculitis involves inflammation of the aorta and its main branches Two distinct large vessel vasculitidies: temporal (or giant cell) arteritis and takayasu arteritis Temporal (giant cell) arteritis primarily affects older women (>60) and the branches of the common carotid arteries Symptoms of temporal arteritis: jaw pain (jaw claudication), headaches, tenderness along temporal artery Complication of temporal arteritis: blindness Takayasu arteritis mostly affects young Asian women (

Join Devri Velazquez and host, Harper Spero, for a special IG Live event on February 15th at 11:00am EST! Follow @madevisiblestories on Instagram to tune in.   When Devri Velazquez was diagnosed with Takayasu's arteritis at 20 years old, the prognosis was devastating. Doctors didn't think she would live to age 21. On today's episode, we talk about what Devri's life looks like now, ten years after her diagnosis, and what it was like to hear such a scary prognosis when she was first diagnosed. We also talk about why, today, managing her physical stress and setting boundaries is so important, and how owning her identity is so central to the advocacy work she does.  This episode previously aired on July 28th, 2020.  For more information about Devri and her journey with Takayasu's Arteritis, visit our website at madevisiblestories.com/podcast   This podcast aims to change the conversation around invisible illnesses and we need your help! Help support our mission by leaving a review and sharing this episode!  Please note: This podcast is intended to provide information and education and is not intended to provide diagnosis, treatment, prevention, cure, or guarantee. You should consult with a licensed or registered healthcare professional about your individual condition and circumstance.    Join the conversation and connect with us online! Website: madvisiblestories.com Facebook: madevisiblepodcast Instagram: @madevisiblestories LinkedIn: madevisible   Lily CBD's hemp-based CBD oil offers an alternative way to nurture yourself, and can be especially beneficial for relieving anxiety and inflammation. Because Lily CBD focuses on small, single-farm harvests, more nutrients are able to make their way into each bottle. Think of it like a glass of beautiful natural wine from a small family vineyard. Visit lilycbd.com and use code madevisible at checkout for 15% off.    – Podcast Editor & Strategist: @episodeready

#1045-Acometimento cardiovascular da arterite de takayasu by Cardiopapers

Commentary by Dr. Valentin Fuster

Confira os temas do check-up de hoje: tratamento da desidratação e do choque hipovolêmico em adultos, novos critérios ACR/EULAR pro diagnóstico de arterite de Takayasu, uso de corticoide na cirurgia cardíaca pediátrica, benefícios da terapia anti-hipertensiva na gravidez e Ceftazidima com avibactam para tratar bactérias super resistentes.

Commentary by Dr. Valentin Fuster

2022 was a wild year in sumo. Every tournament had a different champ, covid demolished the July basho, Mitakeumi gained and subsequently lost ozeki status, Takayasu broke a million hearts... Join the GSB crew to discuss the best and worst of the year! Stay tuned after the credits for our punishment of the year replay. Also make sure to check out our amateur sumo award show where Jake and Mak were joined by the Sumo Punx and Sake & Sumo's Caleb! Theme music by David Hall via SoundCloud

Acometimento cardiovascular da arterite de takayasu by Cardiopapers

In the August episode of Critical Decisions in Emergency Medicine, Drs. Danya Khoujah and Wendy Chang discuss cervical artery dissection as well as drowning and submersion injury. As always, you'll hear about the hot topics covered in CDEM's regular features, including Takayasu arteritis in Clinical Pediatrics, Lisfranc amputation after a crush injury in Critical Cases in Orthopedics and Trauma, clogged feeding tube management in The Critical Procedure, the 2019 update for pediatric advanced life support in The LLSA Literature Review, and the crying infant in The Critical Image.

Meet our latest BINGO winners, and hear our breakdown of the last few days of the basho. We discuss everything from track suits to who we'd want to hire as a bouncer outside our club, Leslie's Bumble dates, the secret to sumo longevity, emotional sumo matches, who we'd want to hot tub with, Paul McCartney, and yes, the sumo, too! More about Sumo Kaboom and our BINGO game: www.sumokaboom.com Twitter @SumoKaboom Instagram https://www.instagram.com/sumokaboom/ Facebook https://www.facebook.com/SumoKaboom/ YouTube https://www.youtube.com/c/SumoKaboomPodcast Check out our ever-changing Sumo Kaboom merch at Red Bubble: SumoKaboom.redbubble.com (https://www.redbubble.com/people/SumoKaboom/explore?page=1&sortOrder=recent) If you'd like to buy us a mawashi or support us monthly, you can sweeten the pot here: https://ko-fi.com/sumokaboom There's no way we could do this without you, so thank you! If you ever wonder where we get our research, check out the Show Notes section of our website.

Tamawashi won this Autumn's Grand Sumo Tournament at Ryogoku over the weekend fending off No.3 Takayasu to become the oldest winner an Emperor's Cup while almost 38 years of age. And the day before, Genki Kawamura won 'Best Director' at the 70th San Sebastian International Film Festival in Spain for his directorial debut Hyakka (A Hundred Flowers) staring Masaki Suda, Mieko Harada, Masami Nagasawa, and Masatoshi Nagase. Learn more about your ad choices. Visit megaphone.fm/adchoices

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In this episode we speak with Dr. Katie Takayasu about the importance of planning ahead for a healthy post-partum. Dr. Katie is an Integrative Medicine physician, author of Plants First: A Physician's Guide to Wellness Through a Plant-Forward Diet, and speaker in the holistic health space, bridging the gap between traditional Western medicine and the evidenced-based complementary health tools of nutrition, acupuncture, meditation, botanicals and lifestyle optimization. She works one-on-one helping patients to recognize their own innate wisdom for finding balance in the mind, body and spirit and in group settings with the gentle but effective Dr. Katie Detox, a jumpstart to reclaiming wellness and lifestyle balance by harnessing the body's natural wisdom for detoxification, available in 5-day and 10-day guided resets. She loves being with other people who bring her joy, especially her husband and two sons. Discover Dr. Katie's Life Kitchen at www.DrKatie.com, on Instagram @DoctorKatie, or in her New Canaan, CT practice. Learning Points: 1. What is the post-partum period? 2. What are key areas to focus on in post-partum? 3. How can eating a plant forward diet support post-partum health? Social Media: https://www.facebook.com/drkatietakayasu https://www.instagram.com/doctorkatie/ https://www.drkatie.com/

On Episode 16 of the Stroke Alert Podcast, Dr. Negar Asdaghi highlights two articles from the May issue of Stroke: “Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage” and “Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia.” She also interviews Dr. Patrick Lyden on “The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.” Dr. Negar Asdaghi:         Let's start with some questions. 1) How is it that stroke can be cured in rodents but not in humans? 2) Are we wasting time or gaining time with general anesthesia before endovascular thrombectomy? 3) My father had an aneurysmal subarachnoid hemorrhage, Doctor. What is my risk of having an aneurysm, and how often should we check for one? We're back here with the Stroke Alert Podcast to tackle the toughest questions in the field because this is the best in Stroke. Stay with us. Dr. Negar Asdaghi:         Welcome back to the May 2022 issue of the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. For the May 2022 issue of Stroke, we have a number of papers that I'd like to highlight. We have seven articles as part of our Focused Update on the topic of neuroimmunology and stroke, organized by our own Stroke editors, Drs. Johannes Boltze and Miguel Perez-Pinzon. We also have an interesting study by Dr. David Saadoun and colleagues from Sorbonne University in Paris, where we learn that in patients with Takayasu disease, how the delay in diagnosis, as defined by the time from symptom onset to the diagnosis being over one year, was significantly associated with development of ischemic cerebrovascular events. In the Comments and Opinions section, we have an interesting study by Dr. Goldenberg and colleagues from University of Toronto on the benefits of GLP-1 receptor agonists for stroke reduction in type 2 diabetes and why should stroke neurologists be familiar with this new class of diabetic medication. Dr. Negar Asdaghi:         Later, in the interview section of the podcast, I have the great honor of interviewing Dr. Patrick Lyden, one of the founding fathers of thrombolytic therapy in stroke, as he walks us through the Stroke Preclinical Assessment Network and what his hopes are for the future of stroke therapy. I also ask him for some advice, and he did tell us about the view from the top, as he truly stands on the shoulder of giants. But first with these two articles. Dr. Negar Asdaghi:         In a landmark population-based study out of Sweden that was published in Brain in 2008, we learned that the odds of development of aneurysmal subarachnoid hemorrhage for individuals with one first-degree relative with a prior history of aneurysmal subarachnoid hemorrhage was 2.15. For individuals with two affected first-degree relatives, the odds ratio was 51. So, it's not surprising that a great deal of anxiety is caused within a family when a relative has an aneurysmal subarachnoid hemorrhage, especially if that family member was young or another member of the family had the same condition before. This scenario is commonly followed by a number of inevitable questions: Should all family members of the affected individual be screened for presence of an intracranial aneurysm? If yes, how often should vascular imaging be performed, and should other aneurysmal risk factors, such as age, sex, smoking, and hypertension, be also considered in the screening decision-making? In this issue of the journal, as part of a derivation-validation study, a group of investigators, led by Dr. Charlotte Zuurbier from University Medical Center at Utrecht Brain Center in the Netherlands, studied the ability of a simple scoring system that was developed in their derivation cohort to predict the presence of an intracranial aneurysm on vascular imaging. Dr. Negar Asdaghi:         They then tested the scoring model in their validation cohort. So, for their development cohort, they used data on 660 persons who were screened at the University Medical Center for presence of an intracranial aneurysm because they had two or more affected first-degree relatives with a prior history of aneurysmal subarachnoid hemorrhage. The median age of participants at the time of first screening was 40, and 59% were female. Dr. Negar Asdaghi:         So, in this cohort, the investigators simply looked at factors that were independently associated with finding an aneurysm on vascular screening by their multivariate analysis. And they identified the following factors; the first factor was the number of affected relatives. Now, a reminder that all of these people in the cohort had at least two first-degree relatives with an aneurysmal subarachnoid hemorrhage. And they found that amongst these people, those that had three or more family members with aneurysmal subarachnoid hemorrhage were significantly more likely to have a positive screening test for intracranial aneurysm. The next factor was older age — the older that relative, the more likely their screening imaging was positive for an aneurysm — and the other independent factors were smoking and hypertension. So they created the NASH acronym; N for number of relatives, A for age, S for smoking, and H for hypertension. When assigning points for each of these factors, the NASH scoring system had a C statistics of 0.68 in predicting whether or not someone would have a positive test, which is an intracranial aneurysm. Dr. Negar Asdaghi:         And now a reminder for our listeners that C statistics gives us the probability that a person with a certain condition, in this case, a certain NASH score, will have the outcome of interest, in this case, an aneurysm found by vascular imaging. In general, for C statistics, the closer we get to 1, the more robust is our predictive model. Values over 0.7 indicate that we have a good model, but values over 0.8 indicate a very strong model. So the NASH score, at 0.68, has a reasonably good capability in predicting who will or will not have an intracranial aneurysm if we complete the vascular imaging. But it's not a very strong model, and this should be kept in mind. Let's look at some of their numbers. In their development cohort, the probability of finding an intracranial aneurysm for a person who scored low on NASH, that is a young person who never smoked and is not hypertensive, was only 5%, whereas the probability of finding an intracranial aneurysm in a person who scored high on NASH, that is an older person in their 60s or 70s, with three or more affected relatives, who is hypertensive and a smoker, was 36%. Dr. Negar Asdaghi:         So, then they tested this NASH score in their external validation cohort and found that the likelihood of identifying an aneurysm increased as expected along the range of predicted probabilities of NASH. That is, the higher the score, the more likely to find an aneurysm on screening with vascular imaging. And the C statistics in the validation cohort was slightly lower than the C statistics in the derivation cohort. So, the important lesson we learned from this study is that the risk of having an intracranial aneurysm in a person who has a first-degree family member with a prior history of aneurysmal subarachnoid hemorrhage is substantially different depending on their NASH score, and this should be taken into consideration when deciding on screening and counseling various family members of the affected patient or prioritizing who should be screened first in routine practice. Dr. Negar Asdaghi:         The ideal anesthetic management during endovascular therapy is still unknown. A number of studies have compared the different anesthetic options available during thrombectomy, which include general anesthesia, or GA, conscious sedation, use of local anesthesia, and no sedation at all. The main argument for doing endovascular therapy under general anesthesia is that although this procedure will take some precious pre-thrombectomy time, it does result in strict immobility. And that is really ideal in the sense that it improves catheter navigation and interpretation of angiography, in addition to obviously providing a secure airway and, of course, avoiding the need to have to do an emergency intubation in case of procedural complications. The argument against general anesthesia is not only the issue of time but also the risk of hypotension and hemodynamic compromise, especially during induction, and the loss of very valuable neurological examination in a completely sedated patient during the procedure. Dr. Negar Asdaghi:         The question is, does general anesthesia improve or worsen neurological and functional outcomes post-thrombectomy? Several smaller randomized trials have looked at this very question, mainly comparing GA to all other forms of sedation during thrombectomy, but they have yielded inconsistent findings regarding the three-month functional outcome. Dr. Negar Asdaghi:         Some of them showed that patients under GA ended up doing better. Some showed no difference in the overall outcomes. But overall, their pooled analysis suggested that GA might be superior to the competing counterpart, which is the conscious sedation, and associated with better functional outcome. But these centers had highly specialized anesthesia teams, and it's possible that their findings may not be generalizable to routine practice. So, in this issue of the journal, using the Swiss Stroke Registry, Dr. Benjamin Wagner from the Department of Neurology at the University Hospital in Basel and colleagues report on the outcomes of endovascularly treated patients in the Swiss Stroke Registry receiving thrombectomy for an anterior circulation stroke with or without general anesthesia. The primary outcome was disability on the modified Rankin Scale after three months. For this study, they excluded one out of the nine centers in the registry that had lots of missing data on their three-month follow-up. Dr. Negar Asdaghi:         And so, from 2014 to 2017, 1,284 patients across eight stroke centers in the registry were included in this study. Sixty-six percent received thrombectomy under general anesthesia. On baseline comparison, the patients in the GA group were older, had a higher NIH Stroke Scale on admission, had worse preclinical functional status, and more likely to have presented with multi-territorial ischemic stroke. So, many reasons as to why people who underwent general anesthesia would have a worse clinical outcome in this study. So, now let's look at their primary outcome. In the unadjusted model, the three-month modified Rankin Scale was significantly worse in the GA group as compared to the non-GA group, which is obviously expected given the differences in their baseline characteristics. Dr. Negar Asdaghi:         But what was surprising was that the odds of having a higher mRS score was significantly greater still in the adjusted models. They also did propensity score matching analysis, and they found that the NIH Stroke Scale after 24 hours, and the odds of dependency and death and mortality were all higher in the adjusted model in the GA group. They also looked at a number of secondary outcomes and found that door-to-puncture time was longer in the GA group. Dr. Negar Asdaghi:         And also these patients were more likely to be transferred to ICU after treatment as compared to the non-GA treated counterparts. The authors point out that these real-world data are in keeping with the findings from the HERMES meta-analysis, which included over 1,700 endovascularly treated patients, and two previously published large registry data, one from Italy, which included over 4,000 endovascularly treated patients, and one from Germany, including 5,808 patients, all of them showing a worse functional outcome in endovascular therapy if the treatment was performed under general anesthesia, as compared to all other forms of sedation or no sedation at all. Again, these findings are in contrast with the reassuring results of the randomized trials on this topic, specifically in contrast to the AnStroke, SIESTA, and GOLIATH randomized trials, which compare GA to conscious sedation, showing either neutral or positive results in favor of general anesthesia pre-thrombectomy. Dr. Negar Asdaghi:         So, in summary, what we learned from this real-world, observational study is that general anesthesia was associated with worse functional outcome post-endovascular thrombectomy, independent of other confounders, which means that the jury is still out on the ideal form of anesthesia for an individual patient prior to endovascular therapy, and we definitely need larger, multicenter studies on this topic. Dr. Negar Asdaghi:         There are over a thousand experimental treatments that have shown benefit in prevention of neurological disability in animal models of ischemic stroke but have failed to show the same efficacy in human randomized trials. In fact, to date, reperfusion therapies, either in the form of intravenous lytic therapies or endovascular treatments, are the only successful treatments available to improve clinical outcomes in patients who suffer from ischemic stroke, and stroke remains a leading cause of death and disability worldwide. How come stroke can be cured in rodents but not in humans? Are neuroprotective therapies, or as more correctly referred to, the cerebroprotective therapies, the epitome of bench-to-bedside translational research failure? And if this is true, what are the key contributors to the scientific conundrum, and how can this be averted in the future? This is the question that a remarkable group of neuroscientists, led by Dr. Patrick Lyden from University of Southern California, are hoping to answer. Dr. Negar Asdaghi:         In this issue of the journal, these investigators describe the rationale, design, feasibility, and stage 1 results of their multicenter SPAN collaboration, which stands for the Stroke Preclinical Assessment Network. I'm joined today by Professor Lyden himself to discuss this collaboration. Now, Professor Lyden absolutely needs no introduction to our stroke community, but as always, introductions are nice. So, here we go. Dr. Lyden is a Professor of Physiology, Neuroscience, and Neurology at Zilkha Neurogenetic Institute, Keck School of Medicine, at USC. He has truly been a leader in the field of preclinical and clinical vascular research with over 30 years of experience in conducting studies and randomized trials, including conducting the pivotal NINDS clinical trial that led to the approval of the first treatment for acute ischemic stroke in 1996. Throughout his exemplary career, he has accumulated many accolades and is the recipient of multiple awards and honors, including the prestigious 2019 American Stroke Association William Feinberg Award for Excellence in Clinical Stroke. Good morning, Pat, it's truly an honor to welcome you to our podcast today. Dr. Patrick Lyden:            Thanks, I'm glad to be here. Dr. Negar Asdaghi:         Well, in the era of successful reperfusion therapies, it seems that the new generation of stroke neurologists and interventionalists have their eyes, so to speak, on the clock and are interested in opening the blood vessels and opening them fast. In the age of reperfusion treatments, why do we still need to talk about the role of cerebroprotective treatments? Dr. Patrick Lyden:            Well, not to sound too glib about it, but not everybody gets better after a thrombectomy. So, thrombectomy is good, it's more effective than anything else that we've tried before, but there are a remaining number of patients with a residual disability. Not only that, and from a more scientific standpoint, thrombectomy offers us the opportunity now to combine cerebroprotective therapy with known reperfusion. Remember, before, we didn't know when the artery had opened, but now we do an embolectomy, we know there's reperfusion. It gives us the opportunity to know that we're combining our treatment with reperfusion. Dr. Negar Asdaghi:         So, in the paper, you discussed how hundreds of treatments have been studied and shown efficacy in reducing neurological disability in animal models of stroke, and yet failed in human studies. In your opinion, what were the top two most disappointing studies in terms of clinical failure despite pre-clinical encouraging data? Dr. Patrick Lyden:            Well, the first one I mentioned was personal because it was the first one that I led, and it was a molecule called clomethiazole that I had helped establish the rationale for in my very first grant. So, it was the first trial I led, it was multinational, and, of course, I firmly believed we were going to hit a home run, and we failed. But to the field, the real watershed moment in neuroprotective therapy was the so-called SAINT II Trial. SAINT II was a study of a drug called NXY-059, and it was the first drug that purportedly had satisfied all of the so-called STAIR criteria. The STAIR criteria came out of a roundtable between academics and industry on how to best qualify drugs preclinically before going to human trials. And the idea was, if you were a 10 out of 10 on the STAIR criteria, then you should win when you come to human clinical trials. And the SAINT II Trial, which I was a co-leader, a co-investigator, on, also failed. Dr. Patrick Lyden:            And so many, many, many drugs had failed by that point. Tens of millions, if not a hundred million dollars, had been spent by industry, and SAINT II really caused the field to stop. Industry stopped investing in stroke; academic investment in stroke dried up. NIH funding became more difficult to get after SAINT II, and that really was sort of the really historical low moment in the development of treatment for stroke. Dr. Negar Asdaghi:         I was a resident when SAINT II came out, and I remember that somber feeling. Dr. Patrick Lyden:            It was a sad day. Dr. Negar Asdaghi:         Yeah. So, in the paper, you outline a number of potential causes as to why this translational failure may have occurred. But you highlighted the absence of preclinical scientific rigor as the most responsible source. And you already alluded to this a little bit. Can you please tell us a bit more? Dr. Patrick Lyden:            Absolutely. And first, of course, we have to say that the ideal clinical trial design is not available. We really don't know the absolute best way to test the drugs in human clinical trials. But leave that for another day. Dr. Patrick Lyden:            On the preclinical side, what can we say we're doing wrong? We're not sure, but one thing that has been highlighted over and over is that we don't approach preclinical characterization with as much rigor as we should. What do I mean by that? Animal models recapitulate for us some of the biology of a stroke, but not all. For example, many, many times we test a drug in a young model, an animal that's quite young, corresponding to a late teenager in human terms. Well, that's ridiculous. Stroke occurs in elderly people, and so on. So, the NIH called in a landmark conference for additional rigor, enhanced rigor. And I should mention the STAIR criteria were a first attempt at this. STAIR put out guidelines that said animals should be elderly, the animals should be randomized, et cetera, et cetera. And so that didn't happen. Although the STAIR criteria were out there, very few laboratories really committed to full rigor. And so the NIH funded the Stroke Preclinical Assessment Network, SPAN, to implement every aspect that we could think of that would add the best possible scientific design, the utmost rigor. So, we implemented true blinded assessment, true randomization, complete case ascertainment where we follow every single subject in the study and account for dropouts and subjects that don't complete the treatment, and, most importantly, a proper statistical design with adequate power and very large numbers. And the hypothesis that we're testing is that additional rigor in SPAN will lead to a better positive predictive value when we think about drugs that should go forward for testing in human stroke trials. Dr. Negar Asdaghi:         So, I think you already answered my next question, which was basically, why do you think SPAN is going to achieve what all others have failed to achieve? But I wanted to simplify and repeat what you mentioned. So, in simple terms, what SPAN is trying to do is to bring all preclinical research to a level of scientific rigor that was not necessarily present and make it a multicenter effort. And can you a little bit tell us about the different stages, again, of SPAN? Dr. Patrick Lyden:            Well, I'm not arguing that all preclinical research needs to be done following a SPAN type of model. Where SPAN fits in is at the end of a development project. So, if you want to characterize the cellular and molecular mechanisms, you don't need to do all of this rigor that we're doing. Just study the drug in the lab and do the mechanistic studies that need to be done. If you want to do dose finding, it doesn't need to be done this way. But at the end of that, OK, first we establish the mechanism, that's the first stage. Then we establish the toxicity. Then we establish target engagement. At the end, we are looking for some evidence that the drug will have a beneficial effect on outcomes. And in previous animal models, the only outcome, generally, the most common outcome that was studied, was size of the stroke. But in humans, the FDA does not recognize stroke size as a valid outcome. Dr. Patrick Lyden:            We look at function, most often measured with the Rankin score and the NIH Stroke Scale. So, we had to create a functional outcome, and then we had to study it at multiple laboratories to make sure we could replicate the effect across multiple sites. And we chose what's called a multi-arm, multi-stage (MAMS) statistical design. All the drugs start out in the experiment at the end of the first interim analysis, which is 25% of the sample size. We cull any compounds or treatments that appear futile are removed. Any that appear effective move on. At the end of the second stage, there's more culling. There's a total of four stages, and we're about to enter stage four, by the way. That's starting next week. And in stage four, there will be, at most, two, maybe only one treatment that has appeared non-futile and possibly effective for final characterization. Dr. Negar Asdaghi:         So, really interesting. I just want to highlight two important comments that you mentioned for our listeners again. So this is multi-layer, as you mentioned, multi-arm, multi-stages. It's sort of filter by filter, just ensuring that what we're seeing, the efficacy we're seeing in preclinical studies, will potentially be replicated in clinical studies. And what you mentioned that's very important is outcomes that classically is measured in animal models are infarct volume that are obviously very important but not necessarily may translate to exactly what we look at in clinical studies, which is functional outcomes, modified Rankin score and NIH Stroke Scale. So, with that, I want to then come back to the treatments that are actually being studied as part of SPAN. You have six very different agents as part of SPAN, from tocilizumab to uric acid. Why do you think these therapies will work? Dr. Patrick Lyden:            Well, my job as the PI of the coordinating center is to remain completely agnostic to the treatments. So, everybody's equal, and they all come in on an equal playing field. We actually have a mechanical treatment called remote ischemic conditioning, as well, and then five drugs. And these were selected through a peer review process at NIH. And then we were informed at the coordinating center what drugs we would be studying. Five drugs and one treatment. And then, of course, the challenge to us was to somehow create a blinded, randomized situation. Now, this turned out to be a fascinating, it's more mechanical, but how do you blind when some of the drugs are given orally, some are given intraperitoneally, some are given intravenously, some are given once, some are given multiple times? So, we had to work with the manufacturers and inventors of these drugs and figure out a way to package them, and in the paper, actually, there's a photograph in the appendix that shows we had to find these bottles that were amber-colored and how to load them and lyophilize the drug. Dr. Patrick Lyden:            And it's actually pretty fascinating how we were able to get all of these different, wildly different therapies, as you say, into a paradigm where they could be tested one against another in a truly blinded, truly randomized way. Dr. Negar Asdaghi:         Do you think you can go on record and say which one is your favorite? Dr. Patrick Lyden:            My favorite drug's not even in SPAN. I am truly agnostic because where my heart is, is with a drug that I've been studying in my laboratory completely separately and not part of SPAN. Dr. Negar Asdaghi:         All right, so we don't have a favorite. So, in a recent review article in Stroke, you commented on treatments used by ancient Persians, Greeks, and Romans to remedy the brain affected by stroke and how the future generation of physicians will look back at our current practices of stroke with the same, how you said, awe and bemusement we hold for Galen, Aristotle, and Avicenna. How do you think stroke will be treated in the year 2222? Dr. Patrick Lyden:            Well, first of all, and to be serious for just one moment, 200 years from now, I worry more about the climate than about medicine. And I really believe our biggest efforts need to be spent on saving the planet. But assuming we make it that long, obviously diagnostic methods will be completely different. Using ionizing radiation to scan the body will be laughed at by physicians in the future. There'll be detection technologies that aren't even on our radar yet today. And then treatments will be cellular focused and regionally focused. We give a drug through a vein and it circulates throughout the entire body, and I'm sure physicians in the future will find a way to somehow get treatment into the part of the body that's injured, not the whole body. And then, who knows? All we can say is they will laugh at us in the same way that we laugh at Theodoric the Barber of York. Dr. Negar Asdaghi:         Let's move on from the future to the past. You're arguably one of the founding fathers of reperfusion therapies. You were instrumental in getting intravenous lytic therapy approved in 1996. It literally took the field 20 years for the next treatment to be approved, that's endovascular treatment. If you could go back in time and give your young self an advice on the subject of research, of course, design and execution, what advice would you give yourself? Dr. Patrick Lyden:            Don't listen to old guys. We got a lot of advice from gray-bearded folks back when we were putting together the tPA trial, and fortunately we ignored some very bad advice and did what we imagined was the right thing to do as young, headstrong up-and-comers do. The other thing is, we really believed that by publishing our science very objectively, without editorial comment, we would be listened to. And that was dead wrong. So, the data was printed in the New England Journal in a very neutral tone, and we felt people would read that data and they would start using tPA the day after the publication. And, as you say, it took 20 years for tPA to really gain widespread acceptance, thrombolytic therapy. Today, people view it as standard, but it wasn't that way at the beginning. And I would say to myself and my colleagues at that time, "Don't be afraid to promote a positive result." Yes, it has to be done with the utmost rigor, but once you have a positive result, there will be plenty of people around pretending they know more than you and telling the world why you are wrong. And it's very important to stand up for your science and stand up for your results and say, no, no, no, no, that interpretation is wrong. The data says what we said it says, and this is an effective treatment and should be used, as an example. Dr. Negar Asdaghi:         What a great advice. Just be bold and say it loud and stand up for your science. Pat, it's been a pleasure interviewing you and having you on the podcast. We really look forward to watching your research. Bring, let me say it again, 2222 closer to now. Dr. Patrick Lyden:            Thank you. Glad to be here. Dr. Negar Asdaghi:         Thank you. Dr. Negar Asdaghi:         And this concludes our podcast for the May 2022 issue of Stroke. Please be sure to check out this month's table of contents for the full list of publications, including two articles on quality improvement in stroke and neurohospitalist—inpatient teleneurology, which comes as part of our Advances in Stroke series prepared by our section editors. And as we close our podcast today, let's take a moment and ask ourselves the same question that I asked Dr. Lyden earlier. What is the next frontier in stroke treatment? Past reperfusion therapies, we have to find ways to preserve the neurons and not just the neurons, all components of the brain. So, is the future of stroke therapy cerebroprotection? Ever since the dawn of history, humanity has lived alongside of death with the conscious apprehension that as we age, we lose the very gift of life. But unlike our ancestors, the search for immortality isn't the quest to find a fountain of youth anymore. We learned that death is inevitable, but with medicine, we can reduce illness and suffering to prolong a life worth living, one with a healthy brain. And today we're closer than ever to this modern immortality with cerebroprotection in stroke, as we stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.  

Commentary by Dr. Valentin Fuster

Y'all, Leslie may never recover from this one. We relive the emotional rollercoaster and recap days 11-15 of the March 2022 basho. More about Sumo Kaboom: www.sumokaboom.com Twitter @SumoKaboom Instagram https://www.instagram.com/sumokaboom/ Facebook https://www.facebook.com/SumoKaboom/ YouTube https://www.youtube.com/c/SumoKaboomPodcast Check out our ever-changing Sumo Kaboom merch at Red Bubble: SumoKaboom.redbubble.com If you'd like to buy us a mawashi or support us monthly, you can sweeten the pot here: https://ko-fi.com/sumokaboom There's no way we could do this without you, so thank you! If you ever wonder where we get our research, check out our Show Notes section of our website.

What happened to our yokozuna? Is Ura in over his head? How did 2019 Takayasu find that time machine? Can Shodai shake off the lingering effects of the plague to stay at ozeki? Will Elon Musk reveal the "sumo champion" he bested, or will he finally admit he just likes to make stuff up to trick people into thinking he's cool? We examine these questions and more in episode 6 of the Sumo Punx Podcast, where we cover the first week of the Grand Sumo March Tournament! Toss some coin into our tip bucket: https://ko-fi.com/sumopunx SUMO PUNX on Twitter: https://twitter.com/PunxSumo And on Instagram: https://www.instagram.com/sumopunx/ And on Facebook: https://m.facebook.com/SumoPunx/ And on YouTube: https://youtu.be/ZSJfEMaD2Jk --- Support this podcast: https://anchor.fm/sumo-punx/support

Crohns' disease and Takayasu's with Artie CardenWe caught up with Artie who joined us in a Sunflower Conversation back 2020. Artie has hypermobility syndrome, Crohn's disease and Takayasu's arteritis. After extended bouts of sickness and diarrhoea Artie sought a medical diagnosis, unfortunately it was this was a misdiagnosis of irritable bowel syndrome which was later changed to a Crohn's.Artie's conditions are autoimmune and result in inflammation across the entire body which can be extremely painful. Artie is on a combination of medications and spends a lot of time researching so that when visiting the doctors is already armed with the information to support the treatment plan.If you are experiencing problems discussed in this podcast contact your GP or healthcare practitioner.For supportCrohn's and Colitis  Check out Artie's social media pagesYouTube.com/c/ArtieCarden Twitter.com/ArtieCarden Instagram.com/ArtieCarden Artiecarden.comFacebook.com/ArtieCarden  Watch and listen to Artie's first Sunflower Conversation with us. Hosted by Paul Shriever and Chantal Boyle, Hidden Disabilities Sunflower.Want to share your story? email conversations@hiddendisabilitiesstore.com

Se inicia la temporada 2022 con la incontestable superioridad del Yokozuna Terunofuji, sin duda el luchador más en forma de todo el sumo actual que buscará hacer olvidar al grandioso Yokozuna Hakuho, que puso fin a su exitosa carrera como luchador en activo hace apenas unos meses. Habrá ausencias de inicio, como la de los sancionados Hidenoumi y Shiden o la de toda la Tagonoura beya, con Takayasu a la cabeza, por temas de coronavirus, noticia que aún no conocíamos en el momento de grabar este audio. De estas cosas y de algunas más os hablamos en esta nueva tertulia en la que Eduardo "Leonishiki" de Paz, Rubén Sánchez, Darío "El Buen Rikishi" y Jordi "minisenpai" Tellez charlan sobre todos estos temas en un programa realizado en directo a través de nuestro canal de Twitch. https://twitch.tv/leonishiki Síguenos en twitter para estar al día de toda la actividad que generamos: https://twitter.com/SumoJapones https://twitter.com/edupaz https://twitter.com/mini_sempai https://twitter.com/elbuenrikishi Toda la información del mundo del sumo la tienes en nuestra web: https://sumojapones.com Únete a la comunidad de aficionados al sumo de habla hispana en Discord: https://discord.gg/y3sV4SR

In this episode of ACR on Air, we continue into part two of our Vasculitis miniseries with Dr. Sharon Chung, lead author of the 2021 ACR/VF guidelines for managing systemic vasculitis. Dr. Chung addresses how the guidelines were developed, the use of use temporal artery biopsy, and the on-going challenges with treating Takayasu's arteritis. She also highlights the success of non-invasive ultrasound techniques in Europe for diagnosing Giant Cell Arteritis (GCA) and discusses the treatment approaches for GCA. 

In this episode, I talk with Dr. Andy Abril, Chair at the Division of Rheumatology at the Mayo Clinic in Jacksonville Florida.  Dr. Abril is one of the lead authors for the 2021 ACR Guidelines on  Takayasu's arteritis. This project was done in partnership with the Vasculitis Foundation. To review the complete guidelines, visit https://dev.vasculitisfoundation.org/2021-acr-vf-vasculitis-guidelines/ or vasculitisfoundation.org. You can find them on Twitter @vasculitisfound and I am @ebrheum. Thanks for listening! 

Being multifaceted in your professional and personal life AND having balance for both, especially in today's world where you want to be your authentic self but virtually connect. And our special guest is an absolute boss when it comes to creating your lane in every aspect that fuels your fire, it's the incredible chronic illness activist, content creator, editor, writer, model and all-around boss woman, Devri Velázquez! In 2011, Devri was diagnosed with a rare disease called Takayasu's arteritis and she used her talents of writing and advocacy work to create a professional resume that rivals many for its diversity and skill. With her unique platform empowering others to create positive changes across communities of gender, race and identity, Devri has written for brands like Allure and 21Ninety.com and been a panelist of health summits. Now with over 96k followers, Devri is the queen of sharing how writing and visuals can empower women to focus on their individual wellness, activism in daily life, and inner powers. In this episode, Devri and Dominique fire off some quick takes about Devri's favorite things like her favorite TikTok trend, how she starts and ends her day with two of the COOLEST things in her routine, and a guilty pleasure she has not shame sharing. Then the duo dives deep and gets real breaking the glass ceiling on misconceptions the diverse chronic illness/disability community deals with—like how to navigate social media while touching on topics of racial and gender inequality, and ways to be a person that advocates for MANY communities because that makes you a passionate badass. Allyship becomes a major chatting point as Devri mentions not only the starting points you can add to be an ally for underrepresented communities, but also how to amplify voices of those in communities like the BIPOC and AAPI communities, because as Dominique points out, being proactive and reactive are two different ways of advocating for change but two very needed styles of allyship! STORY TIME for our Intermission Segment gets a bit spooky and sentimental as Devri tells us about how her love of horror stories resulted in her creating a childhood side hustle that led her down the path as a professional writer today. Get your notepad ready for the second half of the episode because Devri and Dominique create the guidebook of how to be an entrepreneur and be a successful one as your creator and manager, every tip to make your social media a focal point like writing that best caption or taking that perfect photo, and lots of advice of how to create wellness and boundaries to protect your mind and health. Probably the best advice comes from our super uplifting conversation at the end of the episode when Devri mentions how to respond to those social hot button questions about things like racial ignorance, gender inequality and ableism and how to boost your confidence to NEVER be silence when you feel fearful of ‘saying the wrong thing.' They even talk about how ignorance isn't a bad word because that means you can STILL grow and learn from what you don't know. And Devri's BEST piece of advice is so empowering, so powerful, you will want to stick to the end of the episode. Please like, comment, subscribe and share this episode, follow Devri @devrivelazquez, and support InvisiYouth Charity by donating, following and joining our programs and community @invisiyouth!

Sports' greatest comeback has been completed! We chat about Terunofuji's win and how Jake is coping with Takayasu choking... Stay tuned till the end for your voicemails on the yokozuna retirement discussion from last time. Theme music by David Hall via SoundCloud

We break down some of our favorite fights from days 4-10 of the March basho. But, it hard, because there's so much good sumo! If you ever wonder where we get our research, check out our Show Notes (https://sumokaboom.fireside.fm/articles/episode-57-march-basho-days-4-10) Check out our ever-changing Sumo Kaboom merch at Red Bubble (https://www.redbubble.com/people/SumoKaboom/shop?asc=u). Please subscribe or send us a review. It all helps! Thanks. Twitter: @SumoKaboom Facebook: https://www.facebook.com/SumoKaboom/ Instagram: https://www.instagram.com/sumokaboom/ Youtube: https://www.youtube.com/channel/UC0afau4An1hiO69Umr4igKA

Katherine Wehri Takayasu, M.D., M.B.A. practices Integrative Medicine combining traditional Western medicine with evidence-based complementary modalities at Stamford Hospital in Connecticut. She helps patients heal naturally with acupuncture, mind-body medicine, botanical medicine, nutrition, and lifestyle optimization. She is an Assistant Professor of Clinical Medicine at Columbia University/New York Presbyterian and teaches the next generation of doctors about healing the whole patient mind, body and spirit. For her own wellbeing, Dr. Katie practices what she preaches. She engages in yoga and meditation regularly and enjoys experimenting with plant-based cuisine in the kitchen. Visit Dr. Katie at www.DrKatie.com to discover Dr. Katie’s Life Kitchen and on Instagram @DoctorKatie. Look for her book on living a plant-forward lifestyle to be published in 2021.

Dr. Katie shares a personal story of creating awareness around her own health, seeking balance in lifestyle and her pursuit of her passion for sharing health and wellness with her patients. We discuss lifestyle, nutrition, detox, acupuncture, spirituality, meditation, nutrition to lower inflammation and the idea of living a plant forward life. Join us for this fun and informative conversation with Dr. Katie.

What do wrestlers need before a sumo match? Shiko! Power water! Salt! Belly thwacks! Shuffles! Crab walks! Big flexes! And so much more! We breakdown the rituals that come from Shinto and the individual rituals we all love to watch.

Episode Notes Support Disability After Dark by pledging to the patreon. www.patreon.com/disabilityafterdark In this episode, I sit down with Artie Carden, a Youtuber from Brighton, UK. We talk about their experiences getting diagnosed with Crohn’s, BPD, Takayasu’s, fatphobia in the medical system, how disability impacts friendships and relationships.  We talk about accessibility, clothing, Artie’s second bumhole and a whole lot more.   Enjoy! Follow Artie’s work at www.artiecarden.com  Apply now to be on Disability After Dark by e-mailing disabilityafterdark@gmail.com  You can get 50% off almost any item in store at www.adameve.com and 10 FREE GIFTS by using DARKPOD at check out! You can get 15% off your order at ComeAsYouAre.com by using coupon code AFTERDARK

This episode covers takayasu's arteritis!

Imaging is an important aspect in the diagnosis and monitoring of large vessel vasculitides, including Takayasu and giant cell arteritis. However, traditional imaging modalities have consistently posed setbacks in terms of diagnostic accuracy for these conditions. Our featured guest on this episode Anisha Dua, MD, gives us a brief insight into the various challenges observed with large vessel vasculitis imaging, particularly temporal artery biopsy, and how the inclusion of certain modalities, including ultrasound and magnetic resonance imaging (MRI), may improve diagnosis in these patients and our understanding of large vessel vasculitis.

New to November's sanyaku (though 2 of these guys have been here before), THE 3 T's. Which wrestler is nicknamed Riceball? Which one is known for his big feet? Which one fears ghosts? Which one used to play the lead in his school plays? There's oh so much delightful information to share about these boys!

About Sheila: A 60 year old polyamorous pansexual woman. She has been on oxygen for 5 years due to rare diseases (CTEPH and Takayasu’s Arteritis) that have caused her to have very little circulation to her lungs. "I see it as just another fact of life. Being disabled hasn’t changed who I am. I still want to be seen as a vibrant, capable and sexy woman. It has been hard to feel sexy when you are attached to a hose all the time. I did a boudoir photo shoot for my sexy 60 birthday in January. I had them include my oxygen in most of the photos. It was a beautiful experience, and they made my oxygen sexy and beautiful." (Thank you Silk and Salt Photography)Full interview can be viewed on Patreon.com/AmourologyEdAmourologyEd: Sex and Alternative Lifestyle Education and Coaching Inspiring sexual and emotional wholeness through practical and compassionate training.Like and Subscribe for more information on sex, sexuality, gender, relationships, and emotional wholeness.Check out my website for more more information, to book a coaching session, or to schedule an in person workshopAges 17+ Email: Krista@amourology.net Etsy: https://www.etsy.com/shop/AmourologyEdWebsite: https://www.amourology.net/@AmourologyEd on Facebook, Twitter, InstagramFacebook Group: https://www.facebook.com/groups/AmourologyEd/Patreon: https://www.patreon.com/join/AmourologyEd?Podcasts: http://podcast.amourology.net/or wherever podcasts are found (AmourologyEd: Sex and Alternative Lifestyle Education)Videos: @AmourologyEd on YouTubeSupport the show (http://www.patreon.com/join/AmourologyEd?)

Lots of news happened this week in the sumo world, from baby announcements to daring escapes and Abi. We break it all down and try to understand from an outsider's point of view. Plus, help Leslie find her next sumo boyfriend.

When Devri Velazquez was diagnosed with Takayasu's arteritis at 20 years old, the prognosis was devastating. Doctors didn’t think she would live to age 21. On today’s episode, we talk about what Devri’s life looks like now, ten years after her diagnosis, and what it was like to hear such a scary prognosis when she was first diagnosed. We also talk about why, today, managing her physical stress and setting boundaries is so important, and how owning her identity is so central to the advocacy work she does.  Learn more about Devri and check out the show notes here. Follow Made Visible on Instagram. We want to learn more about you! Tell us about you and what got you listening to Made Visible here.  Support for this episode comes from Betterhelp. Betterhelp is an online counseling service that matches you with a licensed professional therapist. No matter where you are in the world, Betterhelp lets you schedule video and phone sessions with your therapist, or even text them. Plus, they’ll work with you to find a counselor you love. It’s not self help, it’s better help. Take 10% off your first month of Betterhelp by visiting https://betterhelp.com/madevisible

No episódio de hoje do Check-up Semanal, nosso programa de atualizações médicas, o editor-chefe médico do Portal PEBMED, Ronaldo Gismondi, comentou sobre as principais novidades divulgadas na última semana. Os temas são: anticorpos na Covid-19, arterite de Takayasu em crianças, volta às aulas após a pandemia, manejo da pancreatite aguda grave e fibrilação atrial. Você que é ouvinte do Check-up Semanal tem um desconto de até 20% no Whitebook! Acesse whitebook.com.br e insira o cupom PEBPODCAST no pagamento da assinatura anual.

The strangest sounding tournament ever. The low-down on what the gyoji are doing. Highlights on days 1 - 7 of the March sumo wrestling tournament.

Josh, Andy and Bruce cover the rikishi competing in the March tournament in Osaka. Who is ready, and who is not. It’s Tachiai’s world famous genki report! We discuss: Takakeisho, Takayasu, Hakuho, Kakuryu, Abi, Yutakayama and Terunofuji! This is the audio version, YouTube video version will appear just above in mere moments….

Join Peter Grayson, MD, MSc, and I as we discuss a range of topics, including imaging in large-vessel vasculitis, doctors going into research, Twitter, rock ‘n’ roll and Disney World. Intro :10 A bit about Peter Grayson :55 Come see me in Phoenix in February 3:35 The interview 4:07 How did you make it to the NIH? 4:27 Why do you think MDs aren’t going into research these days 6:45 Social media and major meetings 9:43 Tell us about the NIH rock ‘n’ roll band 11:10 What imaging modalities are most used for large-vessel vasculitis? 13:32 What is PET scan? 14:23 Do you think PET scanning is the best imaging modality? 15:29 What are the limitations to PET? 17:48 Does vessel size affect PET scanning? 20:01 Are these machines available in most hospitals? 21:12 Grayson’s secret sauce 22:27 How do glucocorticoids affect imaging? 23:19 Are you ever using PET as follow-up? 25:07 Do you have hope for any specific targets for Takayasu’s arteritis? 27:12 What drives the surgical intervention process for these patients? 28:23 Collateral artery formation 30:30 Where do you think Takayasu’s will be in 10 years? 31:35 Thank you, Dr. Grayson 33:36 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Disclosures: Brown and Grayson report no relevant financial disclosures. Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and associate director of the NIAMS Fellowship Program, Systemic Autoimmunity Branch.

As part of our new segmented podcast experiment, here is 20 minutes of Andy and Bruce running through their pre-basho Genki Report, covering the strong, the injured and the broken for the first basho of 2020. We cover Hakuho, Kakuryu, Goeido, Takayasu, The Joi-Jin with special attention to Asanoyama, Abi and Mitakeumi. Audio now, video … Continue reading Hatsu Genki Report Audio Podcast

Devri Velazquez – or, as she has aptly proclaimed herself, “pretty, sick. chick” – is a content creator, writer, editor, speaker, model, and advocate for chronic illness. She lives with a very rare form of vasculitis called Takayasu’s Arteritis. Diagnosed in 2011, she was told by doctors that she might not live to see 30 – and she turned 30 last month! Not only has she defied the odds with her physical health, but her mental health has played a big role in her ongoing wellness and healing. Since diagnosis, she has worked tirelessly to advocate for awareness of this rare disease, connecting with individuals all over the world living with similar conditions. She sat down with Lauren to talk about what motivates her, how she approaches her mindset, and why hard boundaries in her relationships have kept her in good stead. We also touch on gender, ethnicity, and sexual identity as they apply to her medical experience.  Tune in as Devri shares…  - that she was diagnosed during in her last semester of her undergrad degree  - that her early symptoms included brief vision loss, rapid weight loss, jaundice, limp joints, hair loss, and heart palpitations  - that it was confusing to connect the dots of her symptoms – and that at the time she felt like an outsider looking in on her body, disconnected from it entirely  - the revelation that caused her to look into her health more deeply: her mom, a nurse, urged her to go to the hospital  - that it was lucky her parents knew people at the local hospital – because those connections got her a diagnosis within days of checking things out  - that she saw how hard people rallied around her to find an answer  - that she was so sick at diagnosis, she worried she’d die in her sleep  - that she was on bed rest for a full year after diagnosis – which is the antithesis of her personality  - that her partner helped take care of her that first year after diagnosis, which really humbled her  - the importance of asking for help – it’s OK, and it’s necessary  - that as intense as her physical symptoms were, the mental battles that she faced were harder  - some background about Takayasu’s Arteritis  - that the biggest registry for Takayasu’s is in Japan, and consists of about 1,300 patients  - that 1 in 2-3 million people may be at risk for Takayasu’s – so, in essence, she is the only person in Brooklyn living with it  - that she had to get her mind around the idea of death, and come to terms with it  - that she has created discipline around her diet, rest, and relationships  - that when she was diagnosed in her early 20s, medical professionals told her family that the low life expectancy with Takayasu’s meant she had a 40% chance to live 10 more years – and she just turned 30  - that she lives in a constant 8 or 9 on the pain scale, but has learned to accept that level as her 2 or 3  - that she’s learned grace from her experience with chronic pain  - that her pain is focused mainly in her joints, and she occasionally uses a cane as a mobility aid  - that as a freelancer, she is unable to consistently maintain health insurance  - that she takes great inspiration from the world around her  - that she feels more pain when she stands still – which is both a reality and a metaphor for her life  - the role of mindset in her health  - that she would like everyone to have access to healthcare  - that artists and creatives aren’t taken as seriously as others in the healthcare space, and they need to be  - the need for greater compassion in politics and in healthcare  - the burden of her healthcare costs, which make her feel like her chronic illness is a punishment  - her experiences of judgment, harassment, and abuse in the healthcare system as a queer WOC with chronic illness  - how the #MeToo movement has taught her to raise her voice in uncomfortable medical situations  - that she shares her story to remind others they are not alone  - that she experienced her first bout of depression at 13, and has had support from her family since the beginning  - that she utilizes therapy for her mental health, and that she started her own meditation practice at the age of 12 

In this episode I cover vasculitis.If you want to follow along with written notes on vasculitis go to https://zerotofinals.com/medicine/rheumatology/vasculitis/ or the rheumatology section in the Zero to Finals medicine book.This episode cover pathophysiology, presentation, investigations and management of various types of vasculitis, including Henoch-Schonlein purpura, Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome), Microscopic polyangiitis, Granulomatosis with polyangiitis (Wegener's granulomatosis), Polyarteritis nodosa, Kawasaki Disease, Giant cell arteritis, Takayasu's arteritis. The audio in the episode was expertly edited by Harry Watchman.

(Cápsula 018) La arteritis de células gigantes, también conocida como arteritis de la arteria temporal, es una inflamación de los vasos sanguíneos que es más frecuente en personas mayores de 50 años y más en mujeres y personas de raza blanca. La causa de esta enfermedad es desconocida.

(Cápsula 016) Mas que una actualización a las recomendaciones previas de tratamiento de vasculitis de grandes vasos, es un set casi nuevo de recomendaciones que se basa en el conocimiento obtenido de cohortes y estudios aleatorizados en los últimos años. ENLACE: https://ard.bmj.com/content/early/2019/08/03/annrheumdis-2019-215672

This week Introverted Intuition (Jeff,CR,Coco and Laney) are joined by author,model,speaker,and the extremley creative Devri Velazquez to discuss the origns of her relationship with writing,her transition from Texas to New York,what it is living with a chronic disease called Takayasu's,her thoughts on the abortion bill that was passed recently as well as much MUCH more. An extremley inspiring and funny episode. INDULGEFollow Devri on Instagram ASAP- @devrivelazquezFollow the show on Instagram @introvertedintuitionpodSub to our youtube channel youtube.com/introvertedintuitionBookings/Inquires-email introvertedpod@yahoo.com See acast.com/privacy for privacy and opt-out information.

Granulomatous inflammation of the large arteries

Jane Ferguson:                Hello everyone, and happy new year. Welcome to episode 24 of Getting Personal: Omics of the Heart. It's January 2019, I am Jane Ferguson, an assistant professor at Vanderbilt University Medical Center and an associate editor at Circulation Genomic and Precision Medicine. We have a great line-up of papers this month in the journal, so let's jump right into the articles.                                            First up, a paper from Christopher Nelson, Nilesh Samani, and colleagues from the University of Lester entitled, "Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 Inhibitors."                                            I think most listeners are well aware of the efficacy of PCSK9 inhibition in reducing cardiovascular risk. However, as a relatively new treatment option, we do not yet have data on potential long-term side effects of PCSK9 inhibition. In this study, they utilized genetics as a proxy to understand potential long-term consequences of lower PCSK9 activity. They examined a PCSK9 variant that associates with lower LDL, as well as examining two LDL-lowering variants in HMGCR, the target of statins, which served as a positive control of sorts. They used data from over 479,000 individuals in the UK Biobank and looked for associations between the three LDL-lowering variants and 80 different phenotypes.                                            For the PCSK9 variant, the allele which is associated with lower LDL was significantly associated with the higher risk of type 2 diabetes, higher BMI, higher waist circumference, higher waist-hip ratio, higher diastolic blood pressure, as well as increased risk of type 2 diabetes and insulin use. The HMGCR variants were similarly associated with type 2 diabetes as expected.                                            Mediation analysis suggested that the effect of the PCSK9 variant on type 2 diabetes is independent of its effect on obesity. There were nominal associations between the PCSK9 variant and other diseases, including depression, asthma, chronic kidney disease, venous thromboembolism, and peptic ulcer.                                            While genetics cannot fully recapitulate the information that would be gained from long-term clinical follow up, these data suggest that like statins, PCSK9 inhibition may increase the risk of diabetes and potentially other disease. Overall, the cardiovascular efficacy of PCSK9 inhibition may outweigh these other risks, however, future studies should carefully examine these potential side effects.                                            Next up, we have a paper from Xiao Cui, Fang Qin, Xinping Tian, Jun Cai, and colleagues from Peking Uni and Medical College, on "Novel Biomarkers for the Precise Diagnoses and Activity Classification of Takayasu's Arteritis."                                            They were interested in identifying protein biomarkers of Takayasu arteritis, to improve diagnosis and understanding of disease activity in this chronic vascular disease. They ran a proteomic panel including 440 cytokines on 90 individuals, including individuals with active disease, inactive disease, and healthy controls. They found a number of candidates and validated one protein, TIMP-1, as a specific diagnostic biomarker for Takayasu arteritis. For assessing disease activity, there was no single biomarker that could be used for classification, however, the combination of eight different cytokines identified through random forest-based recursive feature elimination and [inaudible] regression, including CA 125, FLRG, IGFBP-2, CA15-3, GROa, LYVE-1, ULBP-2, and CD 99, were able to accurately discriminate disease activity versus inactivity.                                            Overall, this study was able to identify novel biomarkers that could be used for improved diagnosis and assessment of Takayasu arteritis, and may give some clues as to the mechanisms of pathogenesis.                                            Our next paper is entitled, "Familial Sinus Node Disease Caused By Gain of GIRK Channel Function," and comes from Johanna Kuß, Birgit Stallmeyer, Marie-Cécile Kienitz, and Eric Schulze-Bahr, from University Hospital Münster. They were interested in understanding novel genetic underpinnings of inherited sinus node dysfunction.                                            A recent study identified a gain of function mutation in GNB2 associated with sinus node disease. This mutation led to enhanced activation of the G-protein activated inwardly rectifying potassium channel, or GIRK, prompting the researchers to focus their interest on the genes encoding the GIRK subunits, KCNJ3 and KCNJ5. They sequenced both genes in 52 patients with idiopathic sinus node disease, and then carried out whole exome sequencing in family members of patients with potential disease variants in either gene. They identified a non-synonymous variant in KCNJ5, which was not present in the EVS or ExAC databases, and which segregated with disease in the affected family. This variant was associated with increased GIRK currents in a cell system, and in silico models, predicted the variant altered or spermine binding site within the GIRK channel. Thus, this study demonstrated that a gain of function mutation in a GIRK channel subunit associates with sinus node disease, and suggests that modulation of GIRK channels may be a viable therapeutic target for cardiac pacemaking.                                            Our next paper, "Key Value of RNA Analysis of MYBPC3 Splice-Site Variants in Hypertrophic Cardiomyopathy," comes from Emma Singer, Richard Bagnall, and colleagues from the Centenary Institute and the University of Sydney.                                            They wanted to understand the impact of variants in MYBCP3, a known hypertrophic cardiomyopathy gene, on splicing. They recruited individuals with a clinical diagnosis of hypertrophic cardiomyopathy and genetic testing of cardiomyopathy-related genes. They further examined individuals with a variant in MYBCP3 which had an in silico prediction to affect splicing. They sequenced RNA from blood or from fixed myocardial tissue and assessed the relationship between each DNA variant and gene splicing variation.                                            Of 557 subjects, 10% carried rare splice site variants. Of 29 potential variants identified, they examined 9 which were predicted to affect splicing, and found that 7 of these were indeed associated with splicing errors.                                            Going back to the families, they were able to reclassify four variants in four families from uncertain clinical significance to likely pathogenic, demonstrating the utility of using RNA analysis to understand pathogenicity in genetic testing.                                            The next paper this issue comes from Catriona Syme, Jean Shin, Zdenka Pausova, and colleagues from the University of Toronto, and is entitled, "Epigenetic Loci of Blood Pressure: Underlying Hemodynamics in Adolescents and Adults."                                            A recent large meta epigenome-wide association study identified methylation loci that associate with blood pressure. In this study, they wanted to understand more about how these loci related to blood pressure and hemodynamics. They recruited adolescents and middle-aged adults and assessed 13 CPG loci for associations with hemodynamic markers, including systolic and diastolic blood pressure, heart rate, stroke volume, and total peripheral resistance, measured over almost an hour during normal activities. Several of the loci replicated associations with blood pressure, and two of these also showed age-specific associations with hemodynamic variables. One site in PHGDH was particularly associated with blood pressure and stroke volume in adolescents, as well as with body weight and BMI, where lower methylation resulting in higher gene expression associated with higher blood pressure. A second site in SLC7A11 associated with blood pressure in adults but not adolescents, with lower methylation and consequent higher gene expression associated with increased blood pressure.                                            Overall, this study indicates that methylation mediated changes in gene expression may modulate blood pressure and hemodynamic responses in an age-dependent manner.                                            Next up is a research letter from Ben Brumpton, Cristen Willer, George Davey Smith, Bjørn Olav Åsvold, and colleagues from the Norwegian University of Science and Technology, entitled, "Variation in Serum PCSK9, Cardiovascular Disease Risk, and an Investigation of Potential Unanticipated Effects of PCSK9 Inhibition: A GWAS and Mendelian Randomization Study in the Nord-Trøndelag Health Study, Norway."                                            As we heard about from the first study this issue, the long-term side effects of PCSK9 inhibition remain unknown. In this study, they also applied a genetic approach to understand potential unanticipated consequences of PCSK9 inhibition. They analyzed phenotypes from over 69,000 participants in the Nord-Trøndelag Health Study and measured serum PCSK9 in a subset.                                            In PCSK9 GWAS of over 3,600 people, with replication in over 5,000 individuals from the twin gene study. They defined a genetic risk score for serum PCSK9 and assessed the relationship between genetically predicted PCSK9 and outcomes. They saw the expected associations between lower PCSK9 and lower LDL and coronary heart disease risk. However, there was minimal evidence for associations with other outcomes.                                            While our first study in this issue, from Nelson, et al, found that lower PCSK9 from a single genetic variant was associated with higher diabetes risk, this risk was not found here using the genetic risk score. Differences in the genetic definitions and in the populations used can perhaps explain these differences between the two studies, but overall, the studies are consistent in suggesting that long-term PCSK9 inhibition is unlikely to be associated with major adverse outcomes.                                            Our second research letter comes from Young-Chang Kwon, Bo Kyung Sim, Jong-Keuk Lee, and colleagues from Asan Medical Center in Seoul, on behalf of the Korean Kawasaki Disease Genetics Consortium. The title is, "HLA-B54:01 is Associated with Susceptibility to Kawasaki Disease," and reports on novel Kawasaki disease variants.                                            HLA genes have been previously associated with disease, and in this report, the authors sequenced selected axons in HLA-DRB1, HLA-DQB1, HLA-A, HLA-B, HLA-C, and HLA-DBP1 in 160 Kawasaki disease patients and 278 controls. They find a significant association with HLA-B, and replicated this in a sample of 618 Kawasaki disease patients, compared with over 14,000 in-house controls. They identified specific amino acid residues conferring disease susceptibility, highlighting HLA-B as a potential modulator of Kawasaki disease.                                            Our third and final research letter concerns "Serum Magnesium and Calcium Levels and Risk of Atrial Fibrillation: a Mendelian Randomization Study," and comes to us from Susanna Larsson, Nikola Drca, and Karl Michaëlsson, from the Karolinska Institute.                                            Because magnesium and calcium are known to influence atrial fibrillation, this group was interested in whether genetic predictors of serum methyls associated with disease. They constructed genetic predictors from GWAS of calcium in over 61,000 individuals, and GWAS of magnesium in over 23,000 individuals. They applied these predictors to an AF GWAS including over 65,000 cases and over 522,000 controls. Genetically predicted magnesium was inversely associated with atrial fibrillation, while there was no association with genetically predicted calcium.                                            While this study does not definitively prove causality, future studies aimed at assessing whether dietary or other strategies to raise serum magnesium are protective against AF may yield novel strategies for disease prevention.                                            And that's it from us for this month. Thank you for listening, and come back next month for more from Circulation Genomic and Precision Medicine.                                            This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association, 2019.  

What an exciting basho! Takakeisho clinches the Yusho and leaves Takayasu still searching for his first. We talk sumo, take a break for a wholesome breakfast cereal ad at 54:58, and then talk sumo some more. Reach us on social media or leave us a message at 805-613-SUMO (7866). Due to some technical difficulties during the recording, you will notice there are a few audio hiccups throughout the episode. Luckily there aren't too many and they don't last long. We apologize for this -- those responsible have been flogged. Theme music by David Hall via SoundCloud

*Spoilers Through Day 8* Takakeisho is in the lead with six literally hungry rikishi close behind. Will he pull it out or will Takayasu snag his first Yusho? We learn more about what Takanohana has been up to at 32:30 and then answer some twitter questions in our first ever Ask GSB segment. To ask your own question, you can find us on social media or give us a call at 805-613-SUMO (7866). Theme music by David Hall via SoundCloud

Dr. Carolyn Lam:               Welcome to Circulation on the Run. Your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.                                 Today we will be discussing the cost effectiveness of statin use guidelines for the prime and prevention of coronary heart disease and stroke. Comparing the 2013 American College of Cardiology American Heart Association guidelines with the adult treatment panel three guidelines. A very important and current discussion that you don't want to miss. All coming up right after these summaries.                                 The first original paper in this week's journal is the largest study yet reported that assessed the long term outcome of Takayasu's Arthritis. First author, Dr. Comarmond, and corresponding author Dr. Saadoun and colleagues from Hospital Pitie-Salpetriere in Paris performed a retrospective, multi-centered study of 318 patients from the French Takayasu network including patients with Takayasu Arthritis fulfilling the American college of Rheumatology and/or Ishikawa criteria. They found that, firstly, 50% of  Takayasu arthritis patients relapse and experienced a vascular complication at ten years. Secondly, male sex, elevated CRP, and carotidynia were independently associated with relapse and with a two-fold higher risk of relapse. And thirdly, patients at high risk for vascular complications could be identified according to presence of two or more of the following risk factors: progressive clinical course diagnosis, thoracic aortic involvement, and or retinopathy. In summary, these factors identify patients with a high risk of relapse or vascular complications and may therefore serve to adjust more aggressive management and close follow up in Takayasu's Arthritis.                                 The next study provides experimental evidence for a pathogenic role of the transcription factor interferon regulatory factor five or IRF-5 in atherosclerosis. In this study from co-first authors, Dr. Seneviratne and Dr. Edsfeldt, corresponding author Dr. Monoco from Kennedy Institute of Rheumatology in Oxford, United Kingdom, and colleagues. The authors showed that atherosclerosis prone apple-E negative mice who were also deficient in IRF-5 showed reduced atherosclerosis lesions and necrotic core formation. They found that the development of the lesion necrotic core was controlled by IRF-5 through impairment of macrophage dead cell removal, or spherocytosis. They further demonstrated that the CD-11C gene was a direct target of IRF-5 in macrophages and that IRF-5 was important in maintaining CD-11C positive macrophages in atherosclerotic lesions. In summary IRF-5 was shown to be a potential therapeutic target since its inhibition could reduce plaque inflammation and necrotic core size, thus potentially promoting a stable plaque phenotype with a lower risk of acute clinical complications.                                 The next study is the first to assemble a transcriptomic framework of multiple cardiac cell populations during post natal development and following injury, thus enabling comparative analysis of the regenerative or new natal state, compared to the non regenerative or adult state. In this study from first author Dr. Quaife-Ryan and co- corresponding authors Dr. Porrello from the Royal Children's Hospital and Dr. Hudson from the University of Queensland, Australia. The authors isolated cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarct and non infarct neonatal and adult mouse hearts. The then performed RNA sequencing on these cell populations to generate the transcriptome of the major cardiac cell populations during cardiac development, repair and regeneration. They further, surveyed the epigenetic landscape of cardiomyocytes during post natal maturation by performing deep sequencing of assessable chromatin regions. This comprehensive profiling of cardiomyocytes and non myocyte transcriptional programs uncovered several injury responsive genes across regenerative and non regenerative time points. The majority of transcriptional changes in all cardiac cell types resulted from development maturation from neo natal stages to adulthood. Rather that activation of a distinct regeneration specific gene program. Furthermore, adult leukocytes and fibroblasts were characterized by the expression of a proliferative gene expression network following infarction, which mirrored the neonatal state.                                 But in contrast cardiomyocytes failed to reactive the neonatal proliferative network following infarction which was associated with loss of chromatin accessibility around cell cycle genes during post natal maturation. In summary these findings are significant because they defined a regulatory program underpinning the neonatal regenerative state and identified chromatin modifications in adult myocytes that could restrict cardiac regenerative potential after birth and may need to be overcome to facilitate cell cycle re entry in adults.                                 The final study reports results of two studies investigating the pharmicokinetic and clinical outcomes of a new drug coated balloon to treat femoral popliteal disease. The first study is the Illuminate pivotal study in which 300 symptomatic patients were randomized to stellarex drug coated balloon or standard angioplasty. The primary safety outcome was freedom from device and procedure related death through 30 days and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness endpoint was primary patency through 12 months. The second study was the illuminate pharmicokinetic study in which paclitaxel plasma concentrations were measured after last balloon deployment and at pre specified times until no longer detectable. In this report my first in corresponding Dr. Krishnan from Mount Sinai Medical Center in New York. In the pivotal study the primary safety endpoint and the primary patency rate was significantly higher with the drug coated balloon. The rate of clinically driven target lesion revascularization was significantly lower in the drug coated balloon cohort. pharmicokinetic outcomes showed that all patients had detectable Placitexal levels after drug coated balloon deployment that declined within the first hour.                                 In summary these findings demonstrate the safety profile and superior patency of the stellarex drug coated balloon for femoral popliteal disease compared to standard angioplasty. This therefore suggests that this drug coated balloon may be a valuable treatment option for patients with superficial femoral and popliteal artery disease.                                 Well those were your summaries now for our feature discussion.                                 Today we are discussing the highly relevant and also highly controversial issue of Statins for primary prevention of cardiovascular disease and when do we start a statin. How cost effective is it, and of course all this discussion really began with the 2013 ACC/AHA guidelines that expanded the recommended statin use. I am so pleased because this week's journal actually provides, for the first time, some cost effectiveness data that may help us in making this decision and in facing our patients. I can't tell you the number of times I've had an individual patient come to me and just want to discuss all the pros and cons of starting a statin for primary prevention and I'm sure, listeners out there you identify with this. Well hang because today we have the corresponding author of today's feature paper Dr. Kirsten Bibbins-Domingo from University of California, San Francisco  as well as the editorial list on this wonderful paper, Dr. Rodney Hayward from University of Michigan and VA Ann Arbor. Welcome Kirsten and Rod. Dr. Kirsten Bibbins:          Thank you. Dr. Rodney Hayward:     Great to be here. Dr. Carolyn Lam:               Kirsten, could you please tell us the top line results of what you found in this paper, it's such an important paper. Dr. Kirsten Bibbins:          We use simulation modeling to compare three approaches to giving Statins for primary prevention. The older guideline in the US called ATP-3, the one that you mentioned in your introduction the ACC/AHA guideline that broadened the use of Statins to many many more people and then an even broader strategy where we don't look at cardiovascular risk, and in each of these approaches we found that the use of Statins for primary prevention was very effective and in fact cost saving, when we did a cost effectiveness analysis. And regardless of the assumptions that we made about more side effects then we had known from the literature or could anticipate or regardless of the parameters that we put into the model we found that, pretty much that the broad use of these medications is effective and, in fact, cost saving. Dr. Carolyn Lam:               Could you give us an idea of what you used in that simulation model, what population was it, how applicable is it to people outside the US, for example. Dr. Kirsten Bibbins:          Simulation modeling is a way to take the evidence that we have from multiple types of studies and to try to synthesize that evidence and apply it to, in this case, the population of the US. So our simulation model uses the demographics of the US and takes the primary studies and the effect rises that we know from those studies and using that model we found that each of these three approaches had both health benefits and cost saving benefits. It's applicability might be somewhat variable if this were applied to a different population, but the effects are pretty substantial and so it suggests that Statins are likely to be beneficial using these approaches in a broad array of populations. Dr. Carolyn Lam:               Could you give us an idea of the estimated effect size, you know, when you say cost effective, for example, how, how much and for what. Give us everyday clinician some kind of take home of numbers that would make sense for them. Dr. Kirsten Bibbins:          One way to think about these types of cost effectiveness analysis is that often times they give us numbers that suggest that we have to pay a certain amount to get the type of health benefit that we want. In this case because we found that they were cost savings, it actually suggests that the amount that we pay for Statins, to give Statins to a broad population of individuals actually saves us money. It saves us money in terms of the heart attacks that are avoided, and the other types of health care costs that are avoided and probably a number that might be relevant to your audience might be that the number that one would need to treat in order get one additional year of life, through using these Statins for primary prevention, is on the order of about 35 individuals and so that's a small number that we would be treating in a primary care practice in order for an additional quality adjusted year of life. Dr. Carolyn Lam:               I thought that was really one of the most remarkable figures, you know, that the ATP-3 guidelines would result in 8.8 million more statin users than the status quo and that was an entity of 35 per quality of life. Was that correct? Dr. Kirsten Bibbns:           That's exactly right. Dr. Carolyn Lam:               Whereas the ACC/AHA guidelines could potentially result up to 12.3 million more statin users than the ATP-3 guidelines with a marginal number needed of 68 per quality of life. So very, very useful figures, but you know, I began by saying my individual patient. These feel like population bases statistics, you know, and my individual patient kind of wants to know but for me, what's a long term risk and so on. And these are issues that you have discussed so elegantly, Rod, in your editorial. Could you enlighten us a bit on these considerations. Dr. Rodney Hayward:     Sometimes decisions that we have to make in policy are inherently population based decisions, like putting fluoride in the water, in which the average benefit of cost for population is what you have. Cause you can't treat individual separately with that type of intervention, but with a statin, the average that a population gets is not the important thing to our patients across the room. And it's sort of the number needed to treat for them, how likely are they to benefit. And what I think this paper establishes very well, and I think it's important to start with why the areas of agreement here, this establishes that the new guidelines are a great idea. There's no assumptions in this model that would change that starting people on a statin between 7.5 and 10 % ten year risk isn't a good idea. And that aspect of the paper even some of the issues I have about some of the assumptions are not going to be relevant, where it starts to become concerning, and will always be controversial is how low of risk to start it at. Do we go from 7.5 to a 5% risk? Do we start putting everyone at age forty on a statin?                                 And at that case, certain elements of this simulation model are very important, the likelihood of an individual benefiting becomes very, very small. And even a small dislike of the medicine, would outweigh that. But also you have to assume in this model that we know all the bad things of a statin at 20-25 years, because you're starting to put people on a daily medicine that's biologically active for 30 years. And it's impossible statistically, epidemiologically, to know with any degree of certainty whether or not being on these medicines for 20-30 years would have unheard effects. We don't have that ability, currently, even if we had the databases so how should individuals think about that, well my feeling is that is part of the shared decision making of how much a patient worries about unknowns, about being on a medicine long-term versus they worry more about the potential for a heart attack prevention which are likely there. I want to emphasize again these are not relevant concerns when we're talking about the current guidelines, these are only concerns when we start pushing it down to a 5% risk or everyone over 40 where you're extending to tens of millions more people, in which the population benefits would be substantial.                                 As long as people don't mind taking a pill every day at those ages and we know all of the harms being on a statin for 20 years. And that's something that no one knows. Dr. Carolyn Lam:               Rod that was just so eloquently stated, and listeners out there, you just have to read this editorial. It states these things very clearly, and I think it's really helpful in our thinking of what to tell patients when we do see them. Kirsten, I'd love to invite your thoughts on what Rod just said, you acknowledge this, fully in your paper. Curious, any steps you took to maybe address this and what you would say as a take home message for clinicians? Dr. Kirsten Bibbins:          I think that Rod's bringing out exactly the point. And, I think, we have seen the shift from the earlier guideline to the most recent guideline in putting more people on Statins and these medications certainly have the benefit, but as you bring more and more people on who have lower overall cardiovascular risk, their likelihood of benefiting while there, is always smaller. And so then other things do come in to play, and I think the thing that probably was most surprising to us as we put this work together, was how sensitive our results were to, essentially, a patients preference as we moved down into including more of these lower risk individuals. That means that an individual who's lower risk may not directly benefit or their likelihood of benefiting in terms of avoiding a heart attack is lower, and so therefore the facts that their tolerance for taking a daily medication is in fact, then becomes relevant in to their particular trade off for taking this medication. And I think that is clinically important as we think about including more and more lower risk people into these types preventative guidelines, the threshold for any given individuals tolerance for taking a daily medication and of course, as Rod said, if you're doing this over many years and decades the fact that we don't actually know what will happen over the long term, also becomes relevant. Dr. Carolyn Lam:               Just maybe one last question for both of you. What do you think our next step is here, what more do we need? Dr. Kirsten Bibbins:          I just think we still want to continue to expand our understanding of what the long term effects and side effects of daily use of statin therapies are, again I'd want to emphasize as you said it's always important to understand patients preference, but, as Rod said, our current guidelines which really have focused on higher risk individuals, I wouldn't want it to be lost that these medications are in fact very effective and so I think having an understanding of the long term use of these medications and what the potential side effects when used over a long period time are, I think that's a critically important area. As well as really developing continuing to develop the tools that can help doctors and patients together engage in the conversation about the trade off for given individual. Dr. Rodney Hayward:     I would definitely agree with that, but I would focus on three bits of science. That are critically important for refining this issue. The one is something we currently don't have and that's post marketing surveillance of medicines long term. That when you look at the data we have, that, most of them follow patients either a short period of time and don't have enough continuity or their smaller studies in which outcomes that are long term might be found. And this is a place where big data, but also combining and sharing data across health systems could really help us monitor. This is not just an issue for Statins but as more medicines are recommended for younger individuals with life expectancy we need to work on that. Two the results are insensitive meaning that it always looks good, for people in the current guidelines but two elements of the model for people at a 5% risk or starting people at age 40 are assumptions that are being made with the best available data now, but have some considerable concerns and could be improved.                                 One is, we don't know the impact of a non fatal heart attack on future outcomes, my personal opinion is the assumption in this model, is probably an overestimate. Unimportant for the current guidelines but would be critically important for these younger risk people and ways to really understand the impact of non fatal events on future risk are epidemiologically tricky and it's very easy to pick up things that are markers that aren't causal and then when you run your models you think you're extending life years where you really aren't. And the other is we still don't know how much a Statins relative benefit varies by a persons LDL level, that might seem astounding but there's evidence on both sides. That it is related to baseline LDL and it's not. This is a completely solvable question, the CTT group has the data and we really need them to publish and tell us how much the relative risk of a statin varies by that. The current assumption in the ACC/AHA guidelines is that it is not correlated, the assumption in Kirsten's model is that it is.                                 Either could be correct, my personal opinion is it's probably in between, those two, but that would help us in terms of thinking of extending to the lower people. If LDL is a partial factor that probably should be considered, if it's not then only risks should be considered. That is completely answerable for those that have access to the RCT data and I'm hoping that this paper may encourage that publication. Dr. Carolyn Lam:               Wow, those were such insightful comments, I can't thank you enough, Rod and Kirsten for joining us today.                                 Listeners I'm sure you enjoyed that and learned so much just like I did. Don't forget to join us again next week.

I talk with Russ Crandall. After being diagnosed with a severe autoimmune disease know as Takayasu's Arteritis, Russ turned his health around by following a Paleo style diet. Since then he has created some great recipes for his blog thedomesticman.com and just released a cookbook, The Ancestral Table. --- Send in a voice message: https://anchor.fm/aaronolson/message Support this podcast: https://anchor.fm/aaronolson/support