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The last time Yamato was heavily involved on the continent, they were defeated militarily, and they returned to fortify their islands.  So how are things looking, now? This episode we will talk about some of what has been going on with Tang and Silla, but also touch on the Mishihase, the Hayato, the people of Tamna and Tanegashima, and more! For more information and references, check out:  https://sengokudaimyo.com/podcast/episode-140   Rough Transcript   Welcome to Sengoku Daimyo's Chronicles of Japan.  My name is Joshua and this is episode 140: Improving Diplomatic Ties Garyang Jyeongsan and Gim Hongsye looked out from the deck of their ship, tossing and turning in the sea.  The waves were high, and the winds lashed at the ship, which rocked uncomfortably beneath their feet.  Ocean spray struck them from below while rain pelted from above. Through the torrential and unstable conditions, they looked out for their sister ship.  It was their job to escort them, but in these rough seas, bobbing up and down, they were at the mercy of the elements.  One minute they could see them, and then next it was nothing but a wall of water.  Each time they caught a glimpse the other ship seemed further and further away.  They tried calling out, but it was no use—even if they could normally have raised them, the fierce winds simply carried their voices out into the watery void.  Eventually, they lost sight of them altogether. When the winds died down and the seas settled, they looked for their companions, but they saw nothing, not even hints of wreckage on the ocean.  They could only hope that their fellow pilots knew where they were going.  As long as they could still sail, they should be able to make it to land—either to the islands  to which they were headed, or back to the safety of the peninsula. And so the escort ship continued on, even without a formal envoy to escort.  They would hope for the best, or else they would explain what would happen,  and hope that the Yamato court would understand. The seas were anything but predictable, and diplomacy was certainly not for the faint of heart.   We are going through the period of the reign of Ohoama, aka Temmu Tennou.  It started in 672, with the death of his brother, Naka no Oe, remembered as the sovereign Tenji Tenno, when Temmu took the throne from his nephew, Ohotomo, aka Kobun Tenno, in what would become known as the Jinshin no Ran.  From that point, Ohoama continued the work of his brother in creating a government based on a continental model of laws and punishments—the Ritsuryo system.  He accomplished this with assistance from his wife, Uno, and other members of the royal family—his own sons, but also nephews and other princes of the time.  And so far most of our focus has been on the local goings on within the archipelago. However, there was still plenty going on in the rest of the world, and though Yamato's focus may have been on more local affairs, it was still engaged with the rest of the world—or at least with the polities of the Korean Peninsula and the Tang Dynasty.  This episode we are going to look at Yamato's foreign relations, and how they were changing, especially as things changed on the continent. Up to this point, much of what had been happening in Yamato had been heavily influenced by the mainland in one way or another.  And to begin our discussion, we really should backtrack a bit—all the way to the Battle of Baekgang in 663, which we discussed in Episode 124.  That defeat would lead to the fall of Baekje, at the hands of the Silla-Tang alliance.  The loss of their ally on the peninsula sent Yamato into a flurry of defensive activity.  They erected fortresses on Tsushima, Kyushu, and along the Seto Inland Sea.  They also moved the capital up to Ohotsu, a more easily defended point on the shores of Lake Biwa, and likewise reinforced various strategic points in the Home Provinces as well.  These fortresses were built in the style and under the direction of many of the Baekje refugees now resettled in Yamato. For years, the archipelago braced for an invasion by the Silla-Tang alliance.  After all, with all that Yamato had done to support Baekje, it only made sense, from their perspective, for Silla and Tang to next come after them.  Sure, there was still Goguryeo, but with the death of Yeon Gaesomun, Goguryeo would not last that long.  With a unified peninsula, then why wouldn't they next look to the archipelago? And yet, the attack never came.  While Yamato was building up its defenses, it seems that the alliance between Silla and Tang was not quite as strong as their victories on the battlefield may have made it seem.  This is hardly surprising—the Tang and Silla were hardly operating on the same scale.  That said, the Tang's immense size, while bringing it great resources, also meant that it had an extremely large border to defend.  They often utilized alliances with other states to achieve their ends.  In fact, it seems fairly common for the Tang to seek alliances with states just beyond their borders against those states that were directly on their borders.  In other words, they would effectively create a pincer maneuver by befriending the enemy of their enemy.  Of course.  Once they had defeated said enemy well, wouldn't you know it, their former ally was now their newest bordering state. In the case of the Silla-Tang alliance, it appears that at the start of the alliance, back in the days of Tang Taizong, the agreement, at least from Silla's perspective, was that they would help each other against Goguryeo and Baekje, and then the Tang dynasty would leave the Korean peninsula to Silla.  However, things didn't go quite that smoothly.  The fighting against Goguryeo and Baekje can be traced back to the 640s, but Tang Taizong passed away in 649, leaving the throne to his heir, Tang Gaozong.  The Tang forces eventually helped Silla to take Baekje after the battle of Baekgang River in 663, and then Goguryeo fell in 668, but the Tang forces didn't leave the peninsula.  They remained in the former territories of Baekje and in Goguryeo, despite any former agreements.  Ostensibly they were no doubt pointing to the continuing revolts and rebellions in both regions.  While neither kingdom would fully reassert itself, it didn't mean that there weren't those who were trying.  In fact, the first revolt in Goguryeo was in 669.  There was also a revolt each year until 673.  The last one had some staying power, as the Goguryeo rebels continued to hold out for about four years. It is probably worth reminding ourselves that the Tang dynasty, during this time, had reached out on several occasions to Yamato, sending diplomatic missions, as had Silla.  While the Yamato court may have been preparing for a Tang invasion, the Tang perspective seems different.  They were preoccupied with the various revolts going on, and they had other problems.  On their western border, they were having to contend with the kingdom of Tibet, for example.  The Tibetan kingdom had a powerful influence on the southern route around the Taklamakan desert, which abuts the Tibetan plateau.   The Tang court would have had to divert resources to defend their holdings in the western regions, and it is unlikely that they had any immediate designs on the archipelago, which I suspect was considered something of a backwater to them, at the time.  In fact, Yamato would have been much more useful to the Tang as an ally to help maintain some pressure against Silla, with whom their relationship, no longer directed at a common enemy, was becoming somewhat tense. In fact, just before Ohoama came to the throne, several events had occurred that would affect the Silla-Tang alliance. The first event is more indirect—in 670, the Tibetan kingdom attacked the Tang empire.  The fighting was intense, and required serious resources from both sides.  Eventually the Tibetan forces were victorious, but not without a heavy toll on the Tibetan kingdom, which some attribute to the latter's eventual demise.  Their pyrrhic victory, however, was a defeat for the Tang, who also lost troops and resources in the fighting.  Then, in 671, the Tang empire would suffer another loss as Silla would drive the Tang forces out of the territory of the former kingdom of Baekje. With the Baekje territory under their control, it appears that Silla was also working to encourage some of rebellions in Goguryeo.  This more than irked the Tang court, currently under the formal control of Tang Gaozong and the informal—but quite considerable—control of his wife, Wu Zetian, who some claim was the one actually calling most of the shots in the court at this point in time.  Silla encouragement of restoration efforts in Goguryeo reached the Tang court in 674, in and in 675 we see that the Tang forces were sent to take back their foothold in the former Baekje territory.  Tang defeated Silla at Gyeonggi, and Silla's king, Munmu, sent a tribute mission to the Tang court, apologizing for their past behavior. However, the Tang control could not be maintained, as they had to once again withdraw most of their troops from the peninsula to send them against the Tibetan kingdom once more.  As soon as they did so, Silla once again renewed their attacks on Tang forces on the peninsula.  And so, a year later, in 676, the Tang forces were back.  They crossed the Yellow Sea to try and take back the Tang territories on the lower peninsula, but they were unsuccessful.  Tang forces were defeated by Silla at Maeso Fortress in modern day Yeoncheon.  After a bit more fighting, Silla ended up in control of all territory south of the Taedong River, which runs through Pyongyang, one of the ancient capitals of Goguryeo and the capital of modern North Korea.  This meant that the Tang dynasty still held much of the territory of Goguryeo under their control. With everything that was going on, perhaps that explains some of the apparently defensive measures that Yamato continued to take.  For example, the second lunar month of 675, we know that Ohoama proceeded to Takayasu castle, likely as a kind of formal inspection.  Then, in the 10th lunar month of 675 Ohoama commanded that everyone from the Princes down to the lowest rank were to provide the government with weapons.  A year later, in the 9th month of 676, the Princes and Ministers sent agents to the capital and the Home Provinces and gave out weapons to each man.  Similar edicts would be issued throughout the reign.  So in 679 the court announced that in two years time, which is to say the year 681, there would be a review of the weapons and horses belonging to the Princes of the Blood, Ministers, and any public functionaries.  And in that same year, barrier were erected for the first time on Mt. Tatsta and Mt. Afusaka, along with an outer line of fortifications at Naniwa. While some of that no doubt also helped to control internal movements, it also would have been useful to prepare for the possibility of future invasions.  And the work continued.  In 683  we see a royal command to all of the various provinces to engage in military training.  And in 684 it was decreed at that there would be an inspection in the 9th month of the following year—685—and they laid out the ceremonial rules, such as who would stand where, what the official clothing was to look like, etc.  Furthermore, there was also an edict that all civil and military officials should practice the use of arms and riding horses.  They were expected to supply their own horses, weapons, and anything they would wear into battle. If they owned horses, they would be considered cavalry soldiers, while those who did not have their own horse would be trained as infantry.  Either way, they would each receive training, and the court was determined to remove any obstacles and excuses that might arise.   Anyone who didn't comply would be punished.  Non compliance could mean refusing to train, but it could also just mean that they did not provide the proper horses or equipment, or they let their equipment fall into a state of disrepair.  Punishments could range from fines to outright flogging, should they be found guilty.  On the other hand, those who practiced well would have any punishments against them for other crimes reduced by two degrees, even if it was for a capital crime.  This only applied to previous crimes, however—if it seemed like you were trying to take advantage of this as a loophole to be able to get away with doing your own thing than the pardon itself would be considered null and void. A year later, the aforementioned inspection was carried out by Princes Miyatokoro, Hirose, Naniwa, Takeda, and Mino.  Two months later, the court issued another edict demanding that military equipment—specifically objects such as large or small horns, drums, flutes, flags, large bows, or catapults—should be stored at the government district house and not kept in private arsenals.  The "large bow" in this case may be something like a ballista, though Aston translates it to crossbow—unfortunately, it isn't exactly clear, and we don't necessarily have a plethora of extant examples to point to regarding what they meant.  Still, these seem to be focused on things that would be used by armies—especially the banners, large bows, and catapults.  The musical instruments may seem odd, though music was often an important part of Tang dynasty military maneuvers.  It was used to coordinate troops, raise morale, provide a marching rhythm, and more.  Granted, much of this feels like something more continental, and it is unclear if music was regularly used in the archipelago.  This could be more of Yamato trying to emulate the Tang dynasty rather than something that was commonplace on the archipelago.  That might also explain the reference to the Ohoyumi and the catapults, or rock throwers. All of this language having to do with military preparations could just be more of the same as far as the Sinicization of the Yamato government is concerned; attempts to further emulate what they understood of the civilized governments on the mainland—or at least their conception of those governments based on the various written works that they had imported.  Still, I think it is relevant that there was a lot of uncertainty regarding the position of various polities and the potential for conflict.  Each year could bring new changes to the political dynamic that could see military intervention make its way across the straits.  And of course, there was always the possibility that Yamato itself might decide to raise a force of its own. Throughout all of this, there was continued contact with the peninsula and other lands.  Of course, Silla and Goguryeo were both represented when Ohoama came to the throne—though only the Silla ambassador made it to the ceremony, apparently.  In the 7th lunar month of 675, Ohotomo no Muraji no Kunimaro was sent to Silla as the Chief envoy, along with Miyake no Kishi no Irishi.  They likely got a chance to witness first-hand the tensions between Silla and the Tang court.  The mission would return in the second lunar month of the following year, 676.  Eight months later, Mononobe no Muarji no Maro and Yamashiro no Atahe no Momotari were both sent.  That embassy also returned in the 2nd lunar month of the following year. Meanwhile, it wasn't just Yamato traveling to Silla—there were also envoys coming the other way.  For example, in the 2nd lunar month of 675 we are told that Silla sent Prince Chyungweon as an ambassador.  His retinue was apparently detained on Tsukushi while the actual envoy team went on to the Yamato capital.  It took them about two months to get there, and then they stayed until the 8th lunar month, so about four months in total. At the same time, in the third month, Goguryeo and Silla both sent "tribute" to Yamato.  And in the 8th month, Prince Kumaki, from Tamna, arrived at Tsukushi as well.  Tamna, as you may recall, refers to nation on the island known today as Jeju.  The late Alexander Vovin suggested that the name originated from a proto-Japonic cognate with "Tanimura", and many of the names seem to also bear out a possible Japonic influence on the island nation. Although they only somewhat recently show up in the Chronicles from our perspective, archaeological evidence suggests that they had trade with Yayoi Japan and Baekje since at least the first century.  With the fall of Baekje, and the expansion of Yamato authority to more of the archipelago, we've seen a notable uptick in the communication between Tamna and Yamato noted in the record.  A month after the arrival of Prince Kumaki in Tsukushi, aka Kyushu, it is noted that a Prince Koyo of Tamna arrived at Naniwa.  The Tamna guests would stick around for almost a year, during which time they were presented with a ship and eventually returned in the 7th lunar month of the following year, 676.   Tamna envoys, who had also shown up in 673, continued to be an annual presence at the Yamato court through the year 679, after which there is an apparent break in contact, picking back up in 684 and 685. 676 also saw a continuation of Silla representatives coming to the Yamato court, arriving in the 11th lunar month.  That means they probably passed by the Yamato envoys heading the other way.  Silla, under King Mumnu, now had complete control of the Korean peninsula south of the Taedong river.  In the same month we also see another mission from Goguryeo, but the Chronicle also points out that the Goguryeo envoys had a Silla escort, indicating the alliance between Silla and those attempting to restore Goguryeo—or at least the area of Goguryeo under Tang control.  The Tang, for their part, had pulled back their commandary to Liaodong, just west of the modern border between China and North Korea, today.  Goguryeo would not go quietly, and the people of that ancient kingdom—one of the oldest on the peninsula—would continue to rise up and assert their independence for years to come. The chronicles also record envoys from the somewhat mysterious northern Mishihase, or Sushen, thought to be people of the Okhotsk Sea culture from the Sakhalin islands.  There were 11 of them, and they came with the Silla envoys, possibly indicating their influence on the continent and through the Amur river region.  Previously, most of the contact had been through the regions of Koshi and the Emishi in modern Tohoku and Hokkaido.  This seems to be their only major envoy to the Yamato court recorded in this reign. Speaking of outside groups, in the 2nd lunar month of 677 we are told that there was an entertainment given to men of Tanegashima under the famous Tsuki tree west of Asukadera.  Many people may know Tanegashima from the role it played in the Sengoku Period, when Europeans made contact and Tanegashima became a major hub of Sengoku era firearm manufacturing.  At this point, however, it seems that it was still a largely independent island in the archipelago off the southern coast of Kyushu.  Even southern Kyushu appears to have retained some significant cultural differences at this time, with the "Hayato" people being referenced in regards to southern Kyushu—we'll talk about them in a bit as they showed up at the capital in 682.  Tanegashima is actually closer to Yakushima, another island considered to be separate, culturally, from Yamato, and could be considered the start of the chain of islands leading south to Amami Ohoshima and the other Ryukyuan islands.  That said, Tanegashima and Yakushima are much closer to the main islands of the archipelago and show considerable influence, including Yayoi and Kofun cultural artifacts, connecting them more closely to those cultures, even if Yamato initially saw them as distinct in some way. A formal Yamato envoy would head down to Tanegashima two years later, in the 11th lunar month of 679.  It was headed up by Yamato no Umakahibe no Miyatsuko no Tsura and Kami no Sukuri no Koukan.  The next reference to the mission comes in 681, when the envoys returned and presented a map of the island.  They claimed that it was in the middle of the ocean, and that rice was always abundant. With a single sowing of rice it was said that they could get two harvests.  Other products specifically mentioned were cape jasmine and bulrushes, though they then note that there were also many other products that they didn't bother to list.  This must have been considered quite the success, as the Yamato envoys were each awarded a grade of rank for their efforts.   They also appear to have returned with some of the locals, as they were entertained again in Asuka—this time on the riverbank west of Asukadera, where various kinds of music were performed for them. Tanegashima and Yakushima would be brought formally under Yamato hegemony in 702 with the creation of Tane province, but for now it was still considered separate.  This was probably just the first part of the efforts to bring them into Yamato, proper. Getting back to the Silla envoys who had arrived in 676, they appear to have remained for several months.  In the third lunar month of 677 we are told that they, along with guests of lower rank—thirteen persons all told—were invited to the capital.  Meanwhile, the escort envoys and others who had not been invited to the capital were entertained in Tsukushi and returned from there. While this was going on, weather out in the straits drove a Silla boat to the island of Chikashima.  Aboard was a Silla man accompanined by three attendants and three Buddhist priests.  We aren't told where they were going, but they were given shelter and when the Silla envoy, Kim Chyeonpyeong, returned home he left with those who had been driven ashore, as well. The following year, 678, was not a great one for the Silla envoys.  Garyang Jyeongsan and Gim Hongsye arrived at Tsukushi, but they were just the escorts.  The actual envoys had been separated by a storm at sea and never arrived.  In their place, the escort envoys were sent to the capital, probably to at least carry through with the rituals of diplomacy.  This was in the first month of the following year, 679, and given when envoys had previously arrived, it suggests to me that they waited a few months, probably to see if the envoys' ship eventually appeared and to give the court time to figure out what to do.  A month later, the Goguryeo envoys arrived, still being accompanied by Silla escorts, also arrived. Fortunately the Yamato envoys to Silla and elsewhere fared better.  That year, 679, the envoys returned successfully from Silla, Goguryeo, and Tamna.  Overall, though, I think it demonstrates that this wasn't just a pleasure cruise.  There was a very real possibility that one could get lost at sea.  At the same time, one needed people of sufficient status to be able to carry diplomatic messages and appropriately represent the court in foreign lands.  We often seen envoys later taking on greater positions of responsibility in the court, and so you didn't have to go far to find those willing to take the risk for later rewards. That same year, another tribute mission from Silla did manage to make the crossing successfully.  And in this mission we are given more details, for they brought gold, silver, iron, sacrificial cauldrons with three feet, brocade, cloth, hides, horses, dogs, mules, and camels.  And those were just the official gifts to the court.  Silla also sent distinct presents for the sovereign, the queen, and the crown prince, namely gold, silver, swords, flags, and things of that nature. This appears to demonstrate increasingly close ties between Silla and Yamato. All of that arrived in the 10th lunar month of 679, and they stayed through the 6th lunar month of 680—about 7 to 9 months all told, depending on if there were any intercalary months that year.  In addition to entertaining the Silla envoys in Tsukushi—it is not mentioned if they made it to the capital—we are also told that in the 2nd lunar month, halfway through the envoys' visit, eight labourers from Silla were sent back to their own country with gifts appropriate to their station. Here I have to pause and wonder what exactly is meant by this.  "Labourer" seems somewhat innocuous.  I suspect that their presence in Yamato may have been less than voluntary, and I wonder if these were captured prisoners of war who could have been in Yamato now for over a decade.  If so, this could have been a gesture indicating that the two sides were putting all of that nastiness with Baekje behind them, and Yamato was accepting Silla's new role on the peninsula.  Or maybe I'm reading too much into it, but it does seem to imply that Silla and Yamato were growing closer, something that Yamato would need if it wanted to have easy access, again, to the wider world. Speaking of returning people, that seems to have been something of a common thread for this year, 680, as another mission from Goguryeo saw 19 Goguryeo men also returned to their country.  These were condolence envoys who had come to mourn the death of Takara Hime—aka Saimei Tennou.  They must have arrived in the midst of all that was happening peninsula, and as such they were detained.  Their detention is somewhat interesting, when you think about it, since technically Baekje and Goguryeo—and thus Yamato—would have been on the same side against the Silla-Tang alliance.  But perhaps it was just considered too dangerous to send them home, initially, and then the Tang had taken control of their home.  It is unclear to me how much they were being held by Yamato and how much they were just men without a country for a time.  This may reflect how things on the mainland were stabilizing again, at least from Yamato's perspective.  However, as we'll discuss a bit later, it may have also been another attempt at restoring the Goguryeo kingdom by bringing back refugees, especially if they had connections with the old court.  The Goguryeo envoys—both the recent mission and those who had been detained—would remain until the 5th lunar month of 681, when they finally took their leave.  That year, there were numerous mission both from and to Silla and Goguryeo, and in the latter part of the year, Gim Chyungpyeong came once again, once more bearing gives of gold, silver, copper, iron, brocade, thin silk, deerskins, and fine cloth.  They also brought gold, silver, flags of a rosy-colored brocade and skins for the sovereign, his queen, and the crown prince. That said, the 681 envoys also brought grave news:  King Munmu of Silla was dead.  Munmu had reigned since 661, so he had overseen the conquest of Silla and Goguryeo.  His regnal name in Japanese might be read as Monmu, or even "Bunbu", referencing the blending of literary and cultural achievements seen as the pinnacle of noble attainment.  He is known as Munmu the Great for unifying the peninsula under a single ruler—though much of the Goguryeo territory was still out of reach.  Indeed he saw warfare and the betterment of his people, and it is no doubt significant that his death is recorded in the official records of the archipelago.   He was succeeded by his son, who would reign as King Sinmun, though the succession wasn't exactly smooth. We are told that Munmu, knowing his time was short, requested that his son, the Crown Prince, be named king before they attended to Munmu's own funerary arrangements, claiming that the throne should not sit vacant.  This may have been prescient, as the same year Munmu died and Sinmun ascended to the throne there was a revolt, led by none other than Sinmun's own father-in-law, Kim Heumdol.  Heumdol may, himselve, have been more of a figurehead for other political factions in the court and military.  Nonetheless, the attempted coup of 681 was quickly put down—the envoys in Yamato would likely only learn about everything after the dust had settled upon their return. The following year, 682, we see another interesting note about kings, this time in regards to the Goguryeo envoys, whom we are told were sent by the King of Goguryeo.  Ever since moving the commandery to Liaodong, the Tang empire had claimed dominion over the lands of Goguryeo north of the Taedong river.  Originally they had administered it militarily, but in 677 they crowned a local, Bojang as the "King of Joseon", using the old name for the region, and put him in charge of the Liaodong commandery.  However, he was removed in 681, and sent into exile in Sichuan, because rather than suppressing revolt, he had actually encouraged restoration attempts, inviting back Goguryeo refugees, like those who had been detained in Yamato.  Although Bojang himself was sent into exile, his descendants continued to claim sovereignty, so it may have been one of them that was making the claim to the "King of Goguryeo", possibly with Silla's blessing. Later that year, 682, we see Hayato from Ohosumi and Ata—possibly meaning Satsuma—the southernmost point of Kyushu coming to the court in 682.  They brought tribute and representatives of Ohosumi and Ata wrestled, with the Ohosumi wrestler emerging victorious.  They were entertained west of Asukadera, and various kinds of music was performed and gifts were given. They were apparently quite the sight, as Buddhist priests and laiety all came out to watch. Little is known for certain about the Hayato.  We have shields that are attributed to them, but their association may have more to do with the fact that they were employed as ceremonial guards for a time at the palace.  We do know that Southern Kyushu had various groups that were seen as culturally distinct from Yamato, although there is a lot of overlap in material culture.  We also see early reports of the Kumaso, possibly two different groups, the Kuma and So, in earlier records, and the relationship between the Kumaso and the Hayato is not clearly defined. What we do know is that southern Kyushu, for all that it shared with Yamato certain aspects of culture through the kofun period, for example, they also had their own traditions. For example, there is a particular burial tradition of underground kofun that is distinct to southern Kyushu.  A great example of this can be found at the Saitobaru Kofun cluster in Miyazaki, which contains these unique southern Kyushu style burials along with more Yamato style keyhole shaped and circular type kofun.  Miyazaki sits just north of the Ohosumi peninsula, in what was formerly the land of Hyuga, aka  Himuka.  This is also where a lot of the founding stories of the Heavenly grandchild were placed, and even today there is a shrine there to the Heavenly Rock Cave.  In other words there are a lot of connections with Southern Kyushu, and given that the Chronicles were being written in the later 7th and early 8th centuries, it is an area of intense interest when trying to understand the origins of Yamato and Japanese history. Unfortunately, nothing clearly tells us exactly how the Hayato were separate, but in the coming century they would both come under Yamato hegemony and rebel against it, time and again.  This isn't the first time they are mentioned, but it may be the first time that we see them as an actual people, in a factual entry as earlier references in the Chronicles are suspect. Continuing on with our look at diplomacy during this period, the year 683 we see a continuation of the same patterns, with nothing too out of the ordinary.  Same with most of 684 until the 12th lunar month.  It is then that we see a Silla ship arrive with Hashi no Sukune no Wohi and Shirawi no Fubito no Hozen.  They had both, previously been to the Tang empire to study, though we don't have a record of them leaving for that or any other purpose.  They are accompanied by Witsukahi no Muraji no Kobito and Tsukushi no Miyake no Muraji no Tokuko, both of whom had apparently been captured and taken by the Tang dynasty during the Baekje campaign.  Apparently they had all traveled back from the Tang empire together to Silla, who then provided them passage to Yamato. The timing of this suggests it may have had something to do with the changes going on in the Tang empire—changes that I desperately want to get into, but given that we are already a good ways into this current episode, I think I will leave it for later.  But I will note this:  Emperor Gaozong had passed away and his wife, Empress Wu Zetian, was now ruling as regent for her sons.  Wu Zetian is probably the most famous empress in all of Chinese history, and while she held de facto power as a co-regent during her husband's reign and as a regent during her sons' reigns, she would actually ascend the throne herself in 690.  Her reign as a woman during a time of heightened patriarchal tradition is particularly of note, and it leads us to wonder about the vilification that she received by the men who followed her rule.  And I really want to get into all of that but, thematically, I think it better to wait.  Those of you reading ahead in the syllabus—which is to say the Chronicles—probably know why.  So let us just leave it there and say that the Tang was going through a few things, and that may explain why students were returning back in the company of former war captives. A few months later, the Silla escort, Gim Mulyu, was sent home along with 7 people from Silla who had been washed ashore—presumably during a storm or other such event, again illustrating the dangers of taking to the ocean at this time.  Perhaps related to that theme is the entry only a month later, which merely stated that Gim Jusan of Silla returned home.  Gim Jusan was an envoy sent to Yamato in the 11th lunar month of 683.  He was entertained in Tsukushi, and we are told that he returned to his own country on the 3rd month of 684.  Now we are seeing an entry in the 4th month of 685 that this same person apparently returned home. It is possible that something got mixed up, and that the Chroniclers were dealing with a typo in the records that made it seem like this took place a year later than it did.  This was certainly an issue at this time, given all the math one had to do just to figure out what day it was.  There is also the possibility that he returned on another embassy, but just wasn't mentioned for some reason.  The last possible explanation is that he somehow got lost and it took him a year to find his way back.  Not entirely impossible back then, though I am a bit skeptical.  Among other things, why would that note have found its way into the Chronicles in Yamato?  While they were certainly using some continental sources, this seems like something they were talking about as far as him leaving the archipelago, rather than discussion of something happening elsewhere. Speaking of happening elsewhere, I'm wondering about another event that happened around this time as well.  In fact, it was while Gim Mulyu was still in the archipelago.  For some reason the Yamato court granted rank to 147 individuals from Tang, Baekje, and Goguryeo.  Interestingly, they don't mention Silla.  Furthermore, there is no real mention of any Tang envoys during this reign.  In fact, there is hardly mention of the Tang dynasty at all.  There is a mention of some 30 Tang men—captives, presumably—being sent to the Yamato court from Tsukushi.  Those men were settled in Toutoumi, so there were men of Tang in the archipelago.  But beyond that, there are only three other mentions of the Tang dynasty.  One was when the students and war captives came back.  Another was this note about giving rank to 147 individuals.  Finally there is a similar record in 686, at the very end of the reign, where it is 34 persons who were given rank.  This time it was to carpenters, diviners, physicians, students from Tang—possibly those who had just come back a year or so earlier.  So if there weren't envoys from Tang, Goguryeo, and Baekje, who were these people and why were they being granted Yamato court rank?  My assumption is that it was foreigners living in the archipelago, and being incorporated into the Yamato court system.  Still, it is interesting that after the overtures by the Tang in the previous reign we have heard virtually nothing since then.  Again, that is likely largely due to the conflicts between Tang and Silla, though now, things seem to be changing.  The conflicts have settled down, and new rulers are in place, so we'll see how things go. Speaking of which, let's finish up with the diplomatic exchanges in this reign.  I'm only hitting some of the highlights here.  First is the return from Silla, in the 5th month of 685, of Takamuku no Asomi no Maro and Tsuno no Asomi no Ushikahi.  They had traveled to Silla in 684, and they did not come back emptyhanded.  The new King of Silla presented them with gifts, including 2 horses, 3 dogs, 2 parrots, and 2 magpies.  They also brought back the novice monks Kanjou and Ryoukan.  Not bad, overall. Then, 6 months later, another tribute mission came, but this one has an interesting—if somewhat questionable—note attached to it.  It is said that the envoys Gim Jisyang and Gim Geonhun were sent to request "governance" and to bring tribute.  This certainly go the court's attention.  They didn't bring the envoys all the way to the capital, but they did send to them, in Tsukushi, Prince Kawachi, Ohotomo no Sukune no Yasumaro, Fujiwara no Asomi no Ohoshima, and Hodzumi no Asomi no Mushimaro. About three months later they send the musical performers from Kawaradera to provide entertainment during a banquet for the Silla envoy, and in payment some 5,000 bundles of rice rom the private lands attached to the queen's palace were granted to the temple in gratitude. The Silla tribute was then brought to the capital from Tsukushi.  This time it was more than 100 items, including one fine horse, one mule, two dogs, a gold container inlaid with some kind of design, gold, silver, faint brocade, silk gauze, tiger and leopard skins, and a variety of medicines.  In addition, as was now common, the envoys, Gim Jisyang and Gim Geonhun, apparently had personal gifts to give in the form of gold, silver, faint brocade, silk gauze, gold containers, screens, saddle hides, silk cloth, and more medicine.  There were also gifts specifically for the sovereign, the queen, the Crown Prince, and for the various princes of the blood. The court returned this favor with gifts to the envoys, presented at a banquet just for them, before sending them on their way. A couple of notes.  First off, it is interesting that they are entertained at Tsukushi rather than being invited to the capital, and I wonder if this was because the sovereign, Ohoama, wasn't doing so well.  This was all happening in 685 and 686, and the sovereign would pass away shortly afterwards.  So it is possible that Ohoama just was not up to entertaining visitors at this time.  Of course, the Chronicles often don't tell us exactly why a given decision was made, only that it was.  And sometimes not even that. The other thing that seems curious is the mention of a request for governance.  That almost sounds like Silla was asking to come under Yamato hegemony, which I seriously doubt.  It may be that they were asking something along the lines of an alliance, but it is also possible that the scribes recording things for Yamato heard what they wanted to hear and so wrote it down in the light most favorable to Yamato laying claim to the peninsula. Or perhaps I'm misunderstanding exactly what they were asking for.  Maybe "governance" here means something else—perhaps just some kind of better relationship. And with that, we'll leave it for now.  There is more developing in the next reign, but I think we want to wait until we get there.  There are still a lot more things to cover in this reign before we move on—we haven't even touched on the establishment of the new capital, on the various court events, not to mention some of the laws and punishments that this period is named for.  And there is the minor issue of a rebellion.  All of that will be dealt with.  And then, after that, we get to the final reign of the Chronicles: the reign of Jitou Tennou.  From there?  Who knows. It is the winter holiday season, so I hope everyone is enjoying themselves.  Next episode will be the New Year's recap, and then we should finish with this reign probably in January or early February. Until then, 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.

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

In this episode, Brad W. Minton speaks with Melissa Grabiner about leveraging LinkedIn for early career professionals. They discuss the importance of having an optimized LinkedIn profile, engaging with the platform, and networking effectively to enhance job search success. Melissa shares practical tips on how to stand out to recruiters, the significance of being proactive in job searching, and the value of building connections. The conversation emphasizes the need for young professionals to take charge of their career paths and utilize LinkedIn as a powerful tool for growth and opportunity.Key takeawaysLinkedIn is essential for job seekers, especially young professionals.Engagement on LinkedIn can significantly increase visibility to recruiters.A strong profile photo and personalized banner are crucial for attracting attention.Using keywords in your profile can help recruiters find you more easily.Networking is often more effective than applying to job postings.Reaching out to decision-makers can lead to job opportunities that aren't advertised.Being proactive in your job search can set you apart from other candidates.Utilizing LinkedIn Learning can enhance your skills and profile.It's important to share your personal story in your LinkedIn profile.Life is too short to be unhappy at work; seek a fulfilling career.Guest Info:With more than two decades of experience in Human Resources and Talent Acquisition, Melissa Grabiner is widely recognized as a leading strategist and thought leader in the field. She has built a strong reputation for her expertise in Talent Acquisition and has cultivated a LinkedIn following of over 470,000 professionals. Melissa is ranked the #2 Female LinkedIn Creator globally and the #1 HR Creator in the United States.In the past year, her content has generated over 100 million post impressions and almost 2 million post engagements, underscoring her influence as a top voice in the HR and TA spaces. Her thought leadership extends beyond social media, with features in prominent publications including Market Watch, Fast Company, Harvard Business Review, and Indeed Business. She is also a sought-after podcast guest and frequently hosts LinkedIn Live sessions. Her expertise has been spotlighted twice on the iconic Times Square Billboard in New York City.Melissa spent 18 years at Baxter Healthcare, where she led Talent Acquisition for the company's largest global business unit—later acquired by Takeda Pharmaceuticals. Under her leadership, Melissa and her team received numerous awards, including recognition as the highest-performing global HR team at both Baxter and Takeda.Beyond her corporate achievements, Melissa is a passionate Job Search Coach, helping professionals enhance their resumes, optimize LinkedIn profiles, and refine their job search strategies, with perfect testimonials and ratings from every client (over 500). Melissa also works as a Talent Acquisition consultant for companies in the biotechnology and pharmaceutical industries and serves as a Business Advisor to three startup organizations.Melissa holds a bachelor's degree from the University of Illinois at Urbana-Champaign and is a certified yoga instructor and fitness enthusiast. She lives in Chicago with her husband and their two sons.Website: https://topmate.io/melissagrabinerLinkedIn: https://www.linkedin.com/in/melissa-grabiner/This podcast is brought to you by Mint To Be Career. www.minttobecareer.com

JCO Editor-in-Chief Dr. Jonathan Friedberg is joined by colleagues Dr. Jennifer Woyach, Dr. Wojciech Jurczak, and Dr. Matthew Davids to discuss simultaneous publications presented at ASH 2025 on pertibrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Jonathan Friedberg: I'm Jonathan Friedberg, editor of Journal of Clinical Oncology, and welcome to JCO After Hours, where we are covering two manuscripts that were presented at the American Society of Hematology meeting 2025 in Orlando, Florida. I am delighted to be joined by colleagues on this call to discuss these pivotal manuscripts which cover the topic of pirtobrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. I will first just introduce our guests, Dr. Woyach. Dr. Jennifer Woyach: Hi, my name is Jennifer Woyach. I am from the Ohio State University. Dr. Wojciech Jurczak: Hello, I am Wojciech Jurczak, working at the National Research Institute of Oncology in Krakow, Poland. Dr. Matthew Davids: Hi, I am Matthew Davids from Dana-Farber Cancer Institute in Boston. Dr. Jonathan Friedberg: We are going to start by just learning a little bit about these two trials that were both large, randomized phase 3 studies that I think answered some definitive questions. We will start with your study, Jennifer. If you could just describe the design of your study and the patient population. Dr. Jennifer Woyach: Absolutely. So this is the BRUIN CLL-314 study, and this is a phase 3 randomized trial of pirtobrutinib versus ibrutinib in patients with CLL or SLL who had not previously been treated with a covalent BTK inhibitor. The patients were both treatment-naive and relapsed/refractory, about one-third of the patients treatment-naive, the rest relapsed/refractory, and they were stratified based upon 17p deletion and the number of prior lines of therapy. The primary objective was looking at non-inferiority of overall response rate over the entire treated population as well as the relapsed/refractory patient population. Key secondary objectives included progression-free survival in the intention-to-treat and the smaller relapsed/refractory and treatment-naive populations. Dr. Jonathan Friedberg: And just comment a little bit on the risk of the patients. Dr. Jennifer Woyach: This study was fairly typical of this cohort of patients. Within the relapsed/refractory patient population, there was a median of one prior line of therapy in each of the groups, up to nine prior lines of therapy in the patients included on the study. For the overall cohort, about two-thirds of the patients were IGHV unmutated, about 15% had 17p deletion, 30% had TP53 mutations, and about 35% to 40% had a complex karyotype, which is three or more abnormalities. Dr. Jonathan Friedberg: And what were your findings? Dr. Jennifer Woyach: Regarding the primary outcome, which is the focus of the publication, we did find that pirtobrutinib was indeed non-inferior and actually superior to ibrutinib for overall response rate throughout the entire patient population and in both the relapsed/refractory and treatment-naive cohorts. PFS is a little bit immature at this time but is trending towards also being significantly better in pirtobrutinib-treated patients compared with ibrutinib-treated patients. Probably most significantly, we found this to be the case in the treatment-naive cohort where there was a striking trend to an advantage of pirtobrutinib versus ibrutinib. Dr. Jonathan Friedberg: And the follow-up that you have on that progression-free survival? Dr. Jennifer Woyach: So we have about 18 months follow-up on progression-free survival. Dr. Jonathan Friedberg: The second study, Wojciech, can you just go through the design and patient population that you treated? Dr. Wojciech Jurczak: Thank you, Dr. Friedberg, for this question. So the BRUIN CLL-313 study was, in fact, the first phase 3 study with pirtobrutinib in exclusively untreated CLL patients. It was a randomized study where we challenged pirtobrutinib versus bendamustine-rituximab. At the time we designed the protocol, bendamustine-rituximab was an option as a standard of care, and Bruton tyrosine kinase monotherapy was used far more commonly than nowadays. The primary target of the study was progression-free survival. We took all untreated patients except for those with 17p deletions. Therefore, it is a good representation for intermediate risk. We had about 60% of the population, 56 to be precise, which was unmutated, evenly distributed into two treatment arms. 17p deleted cases were excluded, but we had about 7% and 8% of TP53 mutated patients as well as about 11% and 7%, respectively, in the pirtobrutinib and bendamustine-rituximab arm of patients with complex karyotype. The progression-free survival was in favor of pirtobrutinib and was assessed by an independent review committee. What is important is that the progression-free survival of the bendamustine-rituximab arm was actually similar to the other studies addressing the same questions, like the comparison with ibrutinib in the ALLIANCE study or zanubrutinib in the SEQUOIA study. What was different was the hazard ratio. In our study, it was 0.20. It was one of the longest effect sizes noted in the frontline BTK study. It represented an 80% reduction in progression-free survival or death. If we compare it to ibrutinib or zanubrutinib, it was 0.39 and 0.42 respectively. Presumably, this great effect contributed towards a trend of overall survival difference. Although survival data are not mature enough, there is a clear trend represented by three patients we lost in the pirtobrutinib arm versus 10 patients lost in the bendamustine-rituximab arm. This trend in overall survival is becoming statistically significant despite the fact that there was a possibility of crossover, and effectively 52.9 patients, which means 18 out of 34 patients relapsing in the bendamustine-rituximab arm, were treated by pirtobrutinib. Dr. Jonathan Friedberg: I am going to turn it over to Matt. The question is: why study pirtobrutinib in this patient population? And then with these two studies, how do you find the patients that were treated, are they representative of people who you see? And do you see this maybe being approved and more widely available? Dr. Matthew Davids: I think in terms of the first question, why study this in a frontline population, we have seen very impressive data with pirtobrutinib in a very difficult-to-treat population of CLL patients. This was from the original BRUIN phase 1/2 study where most of the patients had at least two or three lines of therapy, often both a covalent BTK inhibitor and the BCL2 inhibitor venetoclax, and yet they were still responding to pirtobrutinib. The drug was also very well tolerated in that early phase experience. And actually, we have seen phase 3 data from the BRUIN 321 study comparing pirtobrutinib to bendamustine and rituximab in a relapse population as well. So I think that really motivated these studies to look at pirtobrutinib as a first therapy. You know, often in other cancers of course, we want to use our best therapy first, and I think these studies are an initial step at looking at that. In terms of the second question around the patient population, these are pretty representative patient populations, I would say, for most frontline CLL studies. We see patients who are a bit younger and fitter than sort of the general population of CLL patients who are treated in clinical practice, and I think that is true here as well. Median age in the sort of mid-60s here is a bit younger than the typical patients we are treating in practice. But that is not different from other CLL frontline studies that we have seen recently, so I think it makes it a little bit easier as we kind of think across studies to feel comfortable that these are relatively similar populations. Dr. Jonathan Friedberg: How do you see this either getting regulatory approval or potentially being used compared to current standard of care options? Dr. Matthew Davids: So my understanding is that both of these trials were designed with registrational intent in the frontline setting, and they are both positive studies. That is certainly very encouraging in terms of the potential for an approval here. We have seen in terms of the FDA recently some concerns around the proportion of patients who are coming from North America, and my understanding is that is relatively low on these two studies. But nonetheless, the datasets are very impressive, and so I think it is certainly supportive of regulatory approval for frontline pirtobrutinib. Dr. Jonathan Friedberg: I will ask Jennifer a question. The control arm in your study was ibrutinib, and I think many in the audience may recognize that newer, second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more frequently used now if monotherapy is decided. How do you respond to that, and how would you put your results in your pirtobrutinib arm in context with what has been observed with those agents? Dr. Jennifer Woyach: Yeah, that is a great question. Even though in the United States we are predominantly using acalabrutinib or zanubrutinib when choosing a monotherapy BTK inhibitor, this is actually not the case throughout the entire world where ibrutinib is still used very frequently. The head-to-head studies of both acalabrutinib and zanubrutinib compared to ibrutinib have shown us pretty well what the safety profile and efficacy profile of the second-generation BTK inhibitors is. So even though we do not have a head-to-head study of acalabrutinib or zanubrutinib versus pirtobrutinib, I think, given the entirety of data that we have with all of the covalent BTK inhibitors, I think we can safely look at the pirtobrutinib arm here, how the ibrutinib arm compares or performs in context with those other clinical trials. And though we really can not say anything about pirtobrutinib versus acalabrutinib or zanubrutinib, I think we can still get a good idea of what might be the clinical scenarios in which you might want to choose pirtobrutinib. Dr. Jonathan Friedberg: And Wojciech, do you agree with that? Obviously, I think you have acknowledged that chemoimmunotherapy is rarely used anymore as part of upfront treatment for CLL. So, I guess a similar question. If you were to put the pirtobrutinib result in your study in context with, I guess, more contemporary type controls, would you agree that it is competitive? Dr. Wojciech Jurczak: Well, I think that that was the last study ever where bendamustine-rituximab was used as a comparator arm. So we should notice that smashing difference. Because if we look at the progression-free survival at two years, we have 93.4% in pirtobrutinib arm versus 70.7% in bendamustine-rituximab arm. Bendamustine-rituximab arm did the same as in the other trials, like ALLIANCE or SEQUOIA. Pirtobrutinib did exceptionally well, as pirto is not just the very best BTK inhibitor overcoming the resistance, but perhaps even more important for the first line, it is very well tolerated and is a very selective drug. Now, if we look at treatment-related adverse events, the discontinuation rate, they were hardly ever seen. If we compared the adverse events in exposure-adjusted incidence, literally all adverse events were two or three times higher in bendamustine-rituximab arm except for the bleeding tendency, which however was predominantly in CTCAE grade 1 and 2 with just 0.7% of grade 3 hemorrhage. Therefore, I think that we should actually put the best and the safest drugs upfront if we may, and pirtobrutinib is, or should be, the first choice if we choose monotherapy. Now, I understand that we are not presenting you the data of pirtobrutinib in combination with anti-CD20 or with BCL2 inhibitors, but that is to come. Dr. Jonathan Friedberg: Matt, how would you envision, were regulatory approval granted and this were an option, using this in the upfront patient population? Is there anybody who you would preferentially use this or start on this treatment? Or would this be something that you would tend to reserve for second line? Dr. Matthew Davids: So I would say that in general for most of my patients who would want to start with a continuous BTK inhibitor, I would still use a covalent BTK inhibitor, and I say that for a couple of reasons despite the very promising data from these studies. The first is that the follow-up for both of these phase 3 trials is still quite short, in the range of a median 18 to 24 months. And we know that CLL is a marathon, not a sprint, and these patients are going to probably be living for a very long time. And we do have much longer follow-up from the covalent BTK inhibitors, median of 10-year follow-up with ibrutinib and five to six years with zanubrutinib and acalabrutinib respectively. And you know, I do not think that the pirtobrutinib is going to fall off a cliff after two years, but on the other hand, I think there is a lot of value to long-term data in this disease, and that is why I think for most of my patients I would stick with covalent BTK inhibitors. But the other important factor that we need to consider is patients who are younger and may have many different CLL treatments over the years. We have to be very careful, I think, about how we sequence these drugs. We know right now that we can start with covalent BTK inhibitors and then subsequently patients will respond well to the non-covalent inhibitor pirtobrutinib in later lines of therapy. But right now we do not have prospective data the other way around. So how will the patients on these studies who progress on pirtobrutinib respond to covalent BTK inhibitors? We do not know yet. There have not been a lot of progression events, which is great, but we would like to see some data in that respect to feel more comfortable with that sequence. Now, I do think that particularly for older patients and those who have significant cardiovascular comorbidities, if they wanted to go on a continuous BTK inhibitor, I do think these data really strongly support using pirtobrutinib as the BTK inhibitor of choice in that population. In particular, the cardiovascular risks with pirtobrutinib seem to be quite low. I was very struck in the comparison with BR that the rate of AFib was equivalent between the two arms of the study. And that is really the first time we have seen that with any of these BTK inhibitors, no elevated risk of AFib in a randomized study. I think that is the population where it will get the most traction first, is the upfront, sort of older patient with significant cardiovascular comorbidities. And as the data from these studies mature, I think that we will start to see more widespread use of pirtobrutinib in the frontline setting. Dr. Jonathan Friedberg: Jennifer, I am just curious if you have any personal experience or heard anecdotally about after progression on pirtobrutinib the use of other BTK inhibitors and whether there is a growing experience there. Dr. Jennifer Woyach: I do not think that there is much clinical experience, you know, as Matt alluded to, it certainly has not been tested yet. There has been some data in relapsed CLL suggesting that in people who have resistance mutations to covalent BTK inhibitors after treatment with pirtobrutinib, sometimes those mutations go away. I think most of us are concerned that they are probably not actually gone but maybe in compartments that we just have not sampled, suggesting that sort of approach where you might sequence a covalent inhibitor after a non-covalent in somebody who had already been resistant probably would not work that well. But, you know, in this setting where people had never been exposed to a covalent BTK inhibitor before, we really have no idea what the resistance patterns are going to be like. We assume they will be the same as what we have seen in relapsed CLL, but I think we just need some longer follow-up to know for sure. Dr. Wojciech Jurczak: If I may confront Dr. Davids about the use of covalent BTK inhibitors upfront, well, I think that we should abandon the idea of using the first and the second and the third generation, at least if we don't have medical lines. If we endlessly block the same pathway, it is not going to be effective. So if pirtobrutinib gets approval in first, second line, we do not necessarily have to use it in the first line. I am not here in a position to defend that we should treat patients with pirtobrutinib upfront and not BCL2 time-limited regimen. However, the way I look at CLL patients when choosing therapy is not just how should I treat them now, but what would be the best regimen in 5, 10 years if I have to re-treat them. And in some instances, the idea may be that in this setting we would like to have a BTK inhibitor upfront to have a BCL2 inhibitor later to make it time-limited. Although I understand and I agree with Matthew that if we have an elderly, fragile population, then the charm of having a drug taken once a day in a tablet with literally few cardiovascular adverse events might be an option. Dr. Jonathan Friedberg: And I will give Matt the last word whether he wants to respond to that, and also just as a forward-looking issue, I know both investigators have implied that there will be future studies looking at combinations with pirtobrutinib, and if you have any sense as to what you would be looking for there. Dr. Matthew Davids: The field really is heading toward time-limited therapy for most patients, I would say. There is a bit of a discrepancy right now in the field between sort of what we are doing in academic practice and what is done sort of more widely in community practice. And so right now we are going to see evolving datasets comparing these approaches. We are already seeing data now from the CLL17 study with ibrutinib comparing continuous to time-limited venetoclax-based therapy, and we are seeing similar efficacy benefits from these time-limited therapies without the need for continuous treatment. And so that is where I think some of the future studies with pirtobrutinib combining it with venetoclax and other partners are so important. Fortunately, several of these studies are already ongoing, including a phase 3 trial called CLL18, which is looking at pirtobrutinib with venetoclax, comparing that to venetoclax and obinutuzumab. So I am optimistic that we are going to be developing these very robust datasets where we can actually use pirtobrutinib in the frontline setting as a time-limited therapy as a component of a multi-drug regimen. So far, those early data are very promising. Dr. Wojciech Jurczak: Perhaps last but not least, in a single center we have treated over 300 patients with pirtobrutinib. So eventually some of them relapsed. And I must say that our experience on BCL2 inhibitors, not just venetoclax but including sonrotoclax, are appealingly good. Therefore, by using pirtobrutinib even earlier, we do not block the efficacy of other compounds. Dr. Jonathan Friedberg: All right. Well, I want to thank all of our speakers. I also want to congratulate our two guests who presented these very influential papers at the ASH Annual Meeting, and chose to publish them in JCO, so we thank you for that, and Dr. Davids for your commentary - really appreciated. That is this episode of JCO After Hours. Thank you for your attention. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Disclosures Dr. Wojciech Jurczak Consulting or Advisory Role: BeiGene, Lilly, Abbvie/Genentech, Takeda, Roche, AstraZeneca Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, AstraZeneca, Lilly, Abbvie/Genentech Dr. Jennifer Woyach Consulting or Advisory Role: Pharmacyclics, Janssen, AstraZeneca, Beigene, Loxo, Newave Pharmaceutical, Genentech, Abbvie, Merck Research Funding: Company name: Janssen, Schrodinger, beone, Abbvie, Merck, Loxo/Lilly Dr. Matthew Davids Honoraria: Curio Science, Aptitude Health, Bio Ascend, PlatformQ Health, Plexus Consulting or Advisory Role: Genentech, Janssen, Abbvie, AstraZeneca, Adaptive Biotechnologies, Ascentage Pharma, BeiGene, Lilly, Bristol-Myers Squibb, Genmab, Merck, MEI Pharma, Nuvalent, Inc., Galapagos NV, Schroedinger Research Funding: Ascentage Pharma, Novartis, MEI Pharma, AstraZeneca  

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

L'Ascesa dei Samurai - Ep. 8 - La Guerra Gempei, Fase 1 – I Fuochi della Ribellione In questa puntata si entra finalmente nel vivo della Guerra Gempei e scopriamo insieme quali sono le prime mosse dei protagonisti, ma soprattutto scopriamo come la fame, i bluff politici e una guerra civile 'dimenticata' all'interno del clan Minamoto abbiano permesso a Yoritomo di fondare il primo Shogunato."La trascrizione è disponibile sul sito:https://www.podcastdelloshogun.itCerca il podcast sui social!https://www.facebook.com/podcastdelloshogunhttps://www.instagram.com/podcastdelloshogun/https://www.tiktok.com/@podcastdelloshogun---Mi trovi anche su Spotify:https://open.spotify.com/show/18pSpwnHNWevxRPaFpXh26Su Apple Podcast:https://podcasts.apple.com/us/podcast/podcast-dello-shogun/id1649546421Su Youtube:https://www.youtube.com/@PodcastDelloShogunSu Spreaker:https://www.spreaker.com/show/podcast-dello-shogun---Se desideri sostenere il podcast, puoi farlo in due modi:- Tramite ko-fi: https://ko-fi.com/podcastdelloshogun- Tramite Paypal: https://paypal.me/podcastdelloshogunFonti: -George Sansom - A History of Japan to 1334 -Stephen Turnbull - The Gempei War 1180-85The founding of the Kamakura shogunate, 1180-1185 - Minoru Shinoda Immagini: Utagawa Kuniyoshi: Minamoto no Yoritomo Ishibashiyama hata-age kassenMusica: Fate Grand Order GudaGuda 8(modified), Sturm un Drang - Samurai Shodown(modified)Capitoli:00:00 - Intro01:20 - Yoritomo a Izu: Matrimonio politico e sollevazione04:46 - La sconfitta militare di Ishibashiyama07:55 - La svolta politica: La sottomissione di Kazusa Hirotsune09:45 - Fujigawa e la strategia del "non inseguimento"12:22 - La guerra civile interna ai Minamoto (Satake e Ashikaga)14:18 - Istituzioni feudali: Wada Yoshimori e il Samurai-dokoro15:23 - La rivolta dei monaci guerrieri e la distruzione del Tōdai-ji18:37 - La Carestia Yōwa (1181-1182)20:25 - Outro#podcast #samurai #shogun #storia #japan #japanese #giappone #giapponese #cultura #medioevo #bushido #kyoto #nippon #history #minamoto #eroi #leggendari #guerra #gempei #legendary #hero #lord #podshogunGuerra Genpei, Guerra Gempei, guerra tra Minamoto e Taira,Minamoto no Yoritomo, Ushiwakamaru, Kiso Yoshinaka, Yoshitsune

A nova vacina de dose única contra dengue do Instituto Butantan marca um avanço histórico no controle da doença no Brasil. Neste episódio do InfectoCast, o infectologista Dr. Ferdinando Lima de Menezes explica como essa vacina foi desenvolvida, quais evidências sustentam sua eficácia e o que muda na prática clínica, no SUS e no manejo das arboviroses.Ao lado do Dr. William Dunke, a conversa aprofunda desde a evolução das vacinas anteriores até os resultados do estudo de fase 3, que acompanhou mais de 16 mil participantes. O episódio esclarece diferenças entre as vacinas da Sanofi, Takeda e Butantan e detalha segurança, efeitos adversos e proteção contra os quatro sorotipos da dengue.

This episode covers: Cardiology This Week: A concise summary of recent studies DAPT: how short is too short Obesity and atrial fibrillation Milestones: COURAGE  Host: Emer Joyce Guests: Carlos Aguiar, Steffen Massberg, Prash Sanders Want to watch that episode? Go to: https://esc365.escardio.org/event/2178 Want to watch that extended interview on dual antiplatelet therapy (DAPT) and shortening its optimal duration, go to: https://esc365.escardio.org/event/2178?resource=interview   Disclaimer  ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails.   Declarations of interests Stephan Achenbach, Yasmina Bououdina, Emer Joyce, Nicolle Kraenkel and Steffen Massberg have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder MyCardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Prashanthan Sanders has declared to have potential conflicts of interest to report: advisory board representative University of Adelaide, Medtronic, Boston Scientific, CathRx, Abbott and Pacemate as well as research grants for University of Adelaide: Medtronic, Abbott, Boston Scientific, Becton Dickson. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

It seems like it's time once more to grab some Japanese film. Especially after the passing of Tatsuya Nakadai. This gives us an excuse to go grab one of his films. So let's grab the three hour Akira Kurosawa film, Kagemusha: The Shadow Warrior(1980). Set before the unification of Japan, we have Tatsuya playing Shingen Takeda and his perfect double. Shingen's regular body double found a criminal that looks like Shingen's twin. A good thing too as lord Takeda get's mortally wounded and begs his generals and the other double to keep the peace for at least three years. This is to keep Oda Nobunaga from becoming emboldened. Spoiler from … Continue reading "Popcorn Pulse 254: Shadow War"

Description: Psoriatic disease affects far more than just the skin. Hear leading dermatologist Dr. April Armstrong and Dr. Benoît Guérrette discuss this and more with Jensen, a patient advocate. Psoriatic disease affects not only the skin but it can impact confidence, emotional and social well-being, and daily life. In this episode, join moderator Dr. Guy Eakin, Chief Scientific and Medical Officer at NPF, as we explore the disconnect between clinical classifications of psoriasis and what patients experience in real-life with leading dermatologist Dr. April Armstrong, Dr. Benoît Guérrette, Vice President of Dermatology & Rheumatology at Takeda, and Jensen, a NPF patient advocate and former Lead Youth Ambassador. Listen as we address the need for a more nuanced approach to classifying disease severity that accounts for the holistic needs of psoriatic disease, as well as share insights into how advocacy and awareness can drive change in treatment access and care standards.  The intent of this episode is to identify how clinical severity classifications of psoriasis are evolving to meet the needs of those who live with the disease and how that change impacts overall management. This episode is sponsored by Takeda. Timestamps: (0:00) Intro to Psoriasis Uncovered and guest welcome to dermatologist Dr. April Armstrong, Vice President of Takeda, Dr. Benoît Guérette, and patient advocate Jensen, who discuss the unmet needs of people with moderate psoriasis and how as a community we can better serve those living with the disease. 2:22 How health care providers and the biopharmaceutical industry are coming together to address systemic eligibility and the unmet needs of people living with psoriasis. 4:25 Quality of life should be included when assessing clinical severity in psoriasis and identification of appropriate treatment choices. 6:52 The impact of misdiagnosis, inappropriate treatment, and effect on high impact sites can be life- altering. 8:30 How appropriate treatment and knowledge can make all the difference when diagnosed with plaque psoriasis.  9:40 Views on the psoriasis disease classification system and how it's evolving to include real life impact from physical and emotional needs, to more personalized care for those living with psoriasis, even when small body surface areas are involved. Severity isn't defined by skin coverage alone. 12:38 What's needed to prioritize the care and outcomes of people living with psoriasis. 14:18  The future of management and care for psoriatic disease. 15:53  "My skin tells a story." Wisdom from what I wish I had known previously. 16:52  Moving closer to care that truly reflects the lives and needs of those who live with psoriasis. Key Takeaways: ·       Severity of psoriasis isn't defined by skin coverage or body surface area (BSA) alone. The impact on quality of life should also be considered in the assessment, selection of treatment, and management of the disease.  ·       The psoriasis disease classification system is evolving to be more of a patient centered approach.  Many clinicians are now using the International Psoriasis Council (IPC) or 2 bucket approach to identify whether someone should receive a topical or systemic treatment based on location and response to treatment, as well as impact on quality of life.  ·       With continued research and  development, the next 5 to 10 years could see a shift in effective treatment options while also treating sooner to initiate better outcomes for people living with psoriasis and psoriatic arthritis. Guest Bios:   April Armstrong, M.D., M.P.H. is an internationally renowned dermatologist and clinical researcher who is a Professor and Chief of Dermatology at the University of California Los Angeles (UCLA) where she specializes in inflammatory skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa (HS). Dr. Armstrong is also the Co-Director for Network Resources at the UCLA Clinical and Translational Research Institute. She has conducted over 150 clinical trials and published over 350 high impact articles in scientific journals. Dr. Armstrong holds multiple leadership positions including the immediate Past Chair of the National Psoriasis Foundation Medical Board, Co-President of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), councilor for the International Psoriasis Council, and board member for the International Dermatology Outcome Measures and the American Academy of Dermatology.  Benoît Guérette, Ph.D. is an accomplished leader in medical affairs with extensive experience across academia and the pharmaceutical industry. Since March 2025, Dr. Guérette has served as Vice President of Dermatology and Rheumatology US Medical Affairs at Takeda Pharmaceutical. Prior to joining Takeda, he held several strategic and leadership roles at various pharmaceutical companies, including overseeing clinical development, global and U.S. medical affairs, global access & pricing, translational sciences and more. Before transitioning to the industry, Dr. Guérette was an Associate Professor of Immunology at Laval University, leading research in cancer immunology. He holds a Ph.D. in Medicine, Microbiology, and Immunology from Laval University and completed postdoctoral studies in Inflammation and Immunology at  Harvard Medical School.  Jensen is a volunteer and former Lead Youth Ambassador for the National Psoriasis Foundation. Jensen developed psoriasis at age 7 but wasn't formally diagnosed until age 14 being misdiagnosed along the way, trying different management approaches that were ineffective. She was a competitive swimmer from elementary through high school and in the last 2 years of high school played lacrosse. Upon finishing high school she attended college becoming a registered nurse in an intensive care unit. Jensen wants "youth living with psoriatic disease to feel a  community that is behind them and with them every step of the way. I really want to be able to make a difference in a way that would've helped me as a child when I was diagnosed." Resources: Ø  "Reassessing Psoriasis Severity" Advance Online, National Psoriasis Foundation. H. Onorati. January 16, 2024,  https://www.psoriasis.org/advance/psoriasis-severity-high-impact-sites/   Ø  "Psoriasis Involving Special Areas is Associated with Worse Quality of Life, Depression, and Limitations in the Ability to Participate in Social Roles and Activities". Blauvelt, A., Strober, B., Gondo, G., Journal of Psoriasis and Psoriatic Arthritis Volume 8, Issue 3.  https://journals.sagepub.com/doi/full/10.1177/24755303231160683

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

La batalla de Kawanakajima de 1561 es una de las batallas más famosas que se produjeron durante el periodo de la Sengoku Jidai en el Japón feudal. En ella, dos grandes daimyos, Uesugi Kenshin y Takeda Shingen, se enfrentaron por cuarta vez en el valle de Kawanakajima, donde ya se habían citado en tres ocasiones para dirimir sus ambiciones y diferencias. A diferencia de los anteriores enfrentamientos, que fueron poco más que tanteos y escaramuzas, en esta cuarta batalla los dos bandos lucharon con un furor y crudeza inusitados. Una estratagema de los Takeda fue genialmente contrarrestada por Uesugi Kenshin, que pilló por sorpresa a una parte del ejército de los Takeda y estuvo a punto de acabar con su daimyo. Sólo la llegada del resto del ejército de los Takeda al combate principal logró equilibrar la situación y acabar el día en un empate tan sangriento como inconcluso. Rubén Ibarzábal, escritor y apasionado divulgador de la Historia del Japón feudal, nos acompaña para hablar de la Sengoku Jidai y de esta batalla en particular. Después, Agustí Barrio y Franjo analizarán Kawanakajima 1561, el primer juego de la serie Batallas de la Sengoku Jidai de Hexasim y precursor del exitoso Tenkatoitsu, que ya tratamos en los inicios de este podcast. Partes: 00:00:00 Presentación 00:33:30 Periodo Sengoku Jidai 01:08:00 Antecedentes de la batalla 01:55:30 Desarrollo de la batalla 02:30:00 Análisis del juego 04:13:00 Conclusiones Tal y como se indica al final del episodio, los audios de terceros se incluyen bajo los acuerdos de ivoox con la SGAE.

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we dive into a series of significant stories shaping the future of healthcare, from innovative financing strategies to groundbreaking scientific advancements.The biotech industry in 2025 has experienced a notable shift in funding strategies, particularly through the rising trend of royalty financing. This approach, involving the exchange of future drug revenue for immediate capital, has surged to approximately $3.5 billion in disclosed upfront volume in just the first half of the year. According to health economist Julien Willard, this represents a transformative shift from a niche option to a mainstream strategy amid challenging equity and credit markets. Royalty financing provides biotech companies with a lifeline, allowing them to avoid the pitfalls of equity dilution or high-interest debt while retaining control over their clinical developments. Firms like Royalty Pharma and Healthcare Royalty Partners are at the forefront, offering upfront cash for future sales royalties, typically ranging from 2.5% to 7.5%.This trend has accelerated due to economic pressures like low stock valuations and rising interest rates, making traditional funding routes less viable. A closer look at this year's deals reveals a cautious approach among investors, who are focusing on phase 3 trials or candidates awaiting FDA approval rather than early-stage assets. Oncology takes center stage as the leading therapeutic area, accounting for about 70% of total disclosed funding, thanks to its potential for large revenue streams. Other areas like rare genetic diseases and immunology also attract significant attention.Interestingly, even large pharmaceutical companies such as Biogen have ventured into royalty financing—an unconventional move for well-capitalized firms. Biogen's collaboration with Royalty Pharma for lupus drug development illustrates innovative financial engineering by transferring clinical trial risk through milestone-tied payments. As this strategy gains traction globally, especially in cash-strapped regions like Asia, it serves as a crucial tool for companies prioritizing survival and continued innovation amidst financial uncertainties.Turning now to regulatory dynamics and strategic shifts within the industry. The legal controversy between GSK's subsidiary Tesaro and AnaptysBio over Jemperli highlights complexities in collaborative agreements within drug development. Such disputes could reshape how companies negotiate intellectual property rights and revenue sharing in future co-development deals.The FDA's investigation into Takeda's Adzynma following a pediatric patient's death underscores the critical role of post-market surveillance in drug safety. This incident could potentially impact Takeda's market position while emphasizing the need for robust adverse event monitoring systems across biopharmaceutical firms.In Australia, the government's decision to block Cosette's proposed $430 million acquisition of Mayne Pharma reflects increasing scrutiny on foreign investments in healthcare companies, prioritizing national interest. This move signals a growing trend that could reshape global M&A strategies within the sector.Meanwhile, Moderna's strategic financial maneuvering is noteworthy. By securing a $1.5 billion loan aimed at supporting its commercial and R&D endeavors with an eye on breaking even by 2028, Moderna demonstrates its commitment to diversifying its mRNA technology applications beyond COVID-19 vaccines—a move likely to influence innovation trajectories across biotech landscapes. Additionally, Moderna's decision to discontinue three clinical mRNA programs showcases strategic pipeline management amidSupport the show

Research shows that women remain woefully underrepresented at the highest levels of leadership in the life sciences industry. Those who have broken through that glass ceiling, however, are not only doing groundbreaking work in pharma, biotech, medtech and beyond but also reframing what it means to be a leader in the sector—as evidenced by the often-unconventional career paths and management philosophies of the 10 women featured in this year’s Fiercest Women in Life Sciences report. In this week’s episode of “The Top Line,” Fierce’s Andrea Park and Gabrielle Masson dive into the report, highlighting several honorees’ paradigm-busting approaches to leadership, mentorship and building inclusive teams. To learn more about the topics in this episode: 2025's Fiercest Women in Life Sciences 4 reasons life sciences still fail women at the top, despite a female-majority workforce: report GSK's Emma Walmsley to step down as CEO in shock move, giving way to commercial lead Luke Miels Merck KGaA, grappling with geopolitical tensions, ⁠reveals CEO transition Takeda taps Julie Kim to take over for retiring CEO Christophe Weber See omnystudio.com/listener for privacy information.

You're in the thick of it. An accident just happened while you were out climbing, and now you have to decide: do I self-rescue, or do I call for outside help? In this episode of the podcast, we dive into that moment of decision, and provide a series of questions that you can use as a matrix to help you decide what to do next. Our guests, Accidents Editor Pete Takeda, and IFMGA/AMGA Guide and Search and Rescue volunteer, Jason Antin, weigh in. Pete reflects on accident reports from ANAC where individuals have self-rescued, called SAR, or had to do a little of both. We break down a few of these case studies to explore what circumstances caused the accident victims to make the decisions they did to initiate rescue. Then, Jason shares what happens behind the scenes when you call Search and Rescue for help, and how self-rescue techniques can supplement a SAR team's mission and help SAR get to an injured party faster. Dive in to help prepare yourself, in case you ever find yourself in that moment of decision on how to respond to an accident. *** If you believe conversations like this matter, a donation to the AAC helps us continue sharing stories, insights, and education for the entire climbing community. Donate today at americanalpineclub.org/donate

This episode covers: Cardiology This Week: A concise summary of recent studies 'ChatGPT, MD?' - Large Language Models at the Bedside Management decisions in myocarditis Statistics Made Easy: Mendelian randomisation Host: Emer Joyce Guests: Carlos Aguiar, Folkert Asselbergs, Massimo Imazio Want to watch that episode? Go to: https://esc365.escardio.org/event/2179 Want to watch that extended interview on 'ChatGPT, MD?': Large Language Models at the Bedside? Go to: https://esc365.escardio.org/event/2179?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Folkert Asselbergs, Yasmina Bououdina, Massimo Imazio, Emer Joyce, and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder MyCardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Emer Joyce Guest: Folkert Asselbergs Want to watch that episode? Go to: https://esc365.escardio.org/event/2179 Want to watch that extended interview on 'ChatGPT, MD?': Large Language Models at the Bedside? Go to: https://esc365.escardio.org/event/2179?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails.  Declarations of interests: Stephan Achenbach, Folkert Asselbergs, Yasmina Bououdina, Emer Joyce, and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder MyCardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. E mma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson. Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED's Health Sciences Advisory Council, interview Evan S. Dellon, MD, and Elizabeth T. Jensen, PhD, about a paper they published on predictors of patients receiving no medication for treatment of eosinophilic esophagitis. Disclaimer: The information provided in this podcast is designed to support, not replace, the relationship between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.   Key Takeaways: [:52] Co-host Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners GSK, Sanofi, Regeneron, and Takeda. Ryan introduces co-host Holly Knotowicz.   [1:14] Holly introduces today's topic, predictors of not using medication for EoE, and today's guests, Dr. Evan Dellon and Dr. Elizabeth Jensen.   [1:29] Dr. Dellon is an Adjunct Professor of Epidemiology at the University of North Carolina School of Medicine in Chapel Hill. He is also the Director of the UNC Center for Esophageal Diseases and Swallowing.   [1:42] Dr. Dellon's main research interest is in the epidemiology, pathogenesis, diagnosis, treatment, and outcomes of eosinophilic esophagitis (EoE) and eosinophilic GI diseases (EGIDs).   [1:55] Dr. Jensen is a Professor of Epidemiology with a specific expertise in reproductive, perinatal, and pediatric epidemiology. She has appointments at both Wake Forest University School of Medicine and the University of North Carolina at Chapel Hill.   [2:07] Her research primarily focuses on etiologic factors in the development of pediatric immune-mediated chronic diseases, including understanding factors contributing to disparities in health outcomes.   [2:19] Both Dr. Dellon and Dr. Jensen also serve on the Steering Committee for EGID Partners Registry.   [2:24] Ryan thanks Dr. Dellon and Dr. Jensen for joining the podcast today.   [2:29] Dr. Dellon was the first guest on this podcast. It is wonderful to have him back for the 50th episode! Dr. Dellon is one of Ryan's GI specialists. Ryan recently went to North Carolina to get a scope with him.   [3:03] Dr. Dellon is an adult gastroenterologist at the University of North Carolina at Chapel Hill. He directs the Center for Esophageal Diseases and Swallowing. Clinically and research-wise, he is focused on EoE and other eosinophilic GI diseases.   [3:19] His research interests span the entire field, from epidemiology, diagnosis, biomarkers, risk factors, outcomes, and a lot of work, more recently, on treatments.   [3:33] Dr. Jensen has been on the podcast before, on Episode 27. Holly invites Dr. Jensen to tell the listeners more about herself and her work with eosinophilic diseases.   [3:46] Dr. Jensen has been working on eosinophilic gastrointestinal diseases for about 15 years. She started some of the early work around understanding possible risk factors for the development of disease.   [4:04] She has gone on to support lots of other research projects, including some with Dr. Dellon, where they're looking at gene-environment interactions in relation to developing EoE.   [4:15] She is also looking at reproductive factors as they relate to EoE, disparities in diagnosis, and more. It's been an exciting research trajectory, starting with what we knew very little about and building to an increasing understanding of why EoE develops.   [5:00] Dr. Dellon explains that EoE stands for eosinophilic esophagitis, a chronic allergic condition of the esophagus.   [5:08] You can think of EoE as asthma of the esophagus or eczema of the esophagus, although in general, people don't grow out of EoE, like they might grow out of eczema or asthma. When people have EoE, it is a long-term condition.   [5:24] Eosinophils are a type of white blood cell, specializing in allergy responses. Normally, they are not in the esophagus. When we see them there, we worry about an allergic process. When that happens, that's EoE.   [5:40] Over time, the inflammation seen in EoE and other allergic cell activity causes swelling and irritation in the esophagus. Early on, this often leads to a range of upper GI symptoms — including poor growth or failure to thrive in young children, abdominal pain, nausea, and symptoms that can mimic reflux.   [5:58] In older kids, symptoms are more about trouble swallowing. That's because the swelling that happens initially, over time, may turn into scar tissue. So the esophagus can narrow and cause swallowing symptoms like food impaction.   [6:16] Ryan speaks of living with EoE for decades and trying the full range of treatment options: food elimination, PPIs, steroids, and, more recently, biologics.   [6:36] Dr. Dellon says Ryan's history is a good overview of how EoE is treated. There are two general approaches to treating the underlying condition: using medicines and/or eliminating foods that we think may trigger EoE from the diet.   [6:57] For a lot of people, EoE is a food-triggered allergic condition.   [7:01] The other thing that has to happen in parallel is surveying for scar tissue in the esophagus. If that's present and people have trouble swallowing, sometimes stretching the esophagus is needed through esophageal dilation.   [7:14] There are three categories of medicines used for treatment. Proton pump inhibitors are reflux meds, but they also have an anti-allergy effect in the esophagus.   [7:29] Topical steroids are used to coat the esophagus and produce an anti-inflammatory effect. The FDA has approved a budesonide oral suspension for that.   [7:39] Biologics, which are generally systemic medications, often injectable, can target different allergic factors. Dupilumab is approved now, and there are other biologics that are being researched as potential treatments.   [7:51] Even though EoE is considered an allergic condition, we don't have a test to tell people what they are allergic to. If it's a food allergy, we do an empiric elimination diet because allergy tests aren't accurate enough to tell us what the EoE triggers are.   [8:10] People will eliminate foods that we know are the most common triggers, like milk protein, dairy, wheat, egg, soy, and other top allergens. You can create a diet like that and then have a response to the diet elimination.   [8:31] Dr. Jensen and Dr. Dellon recently published an abstract in the American Journal of Gastroenterology about people with EoE who are not taking any medicine for it. Dr. Jensen calls it a real-world data study, leveraging electronic health record patient data.   [8:51] It gives you an impression of what is actually happening, in terms of treatments for patients, as opposed to a randomized control trial, which is a fairly selected patient population. This is everybody who has been diagnosed, and then what happens with them.   [9:10] Because of that, it gives you a wide spectrum of patients. Some patients are going to be relatively asymptomatic. It may be that we arrived at their diagnosis while working them up for other potential diagnoses.   [9:28] Other patients are going to have rather significant impacts from the disease. We wanted to get an idea of what is actually happening out there with the full breadth of the patient population that is getting diagnosed with EoE.   [9:45] Dr. Jensen was not surprised to learn that there are patients who had no pharmacologic treatment.   [9:58] Some patients are relatively asymptomatic, and others are not interested in pursuing medications initially or are early in their disease process and still exploring dietary treatment options.   [10:28] Holly sees patients from infancy to geriatrics, and if they're not having symptoms, they wonder why bother treating it.   [10:42] Dr. Jensen says it's a point of debate on the implications of somebody who has the disease and goes untreated. What does that look like long-term? Are they going to develop more of that fibrostenotic pattern in their esophagus without treatment?   [11:07] This is a question we're still trying to answer. There is some suggestion that for some patients who don't manage their disease, we very well may be looking at a food impaction in the future.   [11:19] Dr. Dellon says we know overall for the population of EoE patients, but it's hard to know for a specific patient. We have a bunch of studies now that look at how long people have symptoms before they're diagnosed. There's a wide range.   [11:39] Some people get symptoms and get diagnosed right away. Others might have symptoms for 20 or 30 years that they ignore, or don't have access to healthcare, or the diagnosis is missed.   [11:51] What we see consistently is that people who may be diagnosed within a year or two may only have a 10 or 20% chance of having that stricture and scar tissue in the esophagus, whereas people who go 20 years, it might be 80% or more.   [12:06] It's not everybody who has EoE who might end up with that scar tissue, but certainly, it's suggested that it's a large majority.   [12:16] That's before diagnosis. We have data that shows that after diagnosis, if people go a long time without treatment or without being seen in care, they also have an increasing rate of developing strictures.    [12:29] In general, the idea is yes, you should treat EoE, because on average, people are going to develop scar tissue and more symptoms. For the patient in front of you with EoE but no symptoms, what are the chances it's going to get worse? You don't know.   [13:04] There are two caveats with that. The first is what we mean by symptoms. Kids may have vomiting and growth problems. Adults can eat carefully, avoiding foods that hang up in the esophagus, like breads and overcooked meats, sticky rice, and other foods.   [13:24] Adults can eat slowly, drink a lot of liquid, and not perceive they have symptoms. When someone tells Dr. Dellon they don't have symptoms, he will quiz them about that. He'll even ask about swallowing pills.    [13:40] Often, you can pick up symptoms that maybe the person didn't even realize they were having. In that case, that can give you some impetus to treat.   [13:48] If there really are no symptoms, Dr. Dellon thinks we're at a point where we don't really know what to do.   [13:54] Dr. Dellon just saw a patient who had a lot of eosinophils in their small bowel with absolutely no GI symptoms. He said, "I can't diagnose you with eosinophilic enteritis, but you may develop symptoms." People like that, he will monitor in the clinic.   [14:14] Dr. Dellon will discuss it with them each time they come back for a clinic visit.   [14:19] Holly is a speech pathologist, but also sees people for feeding and swallowing. The local gastroenterologist refers patients who choose not to treat their EoE to her. Holly teaches them things they should be looking out for.   [14:39] If your pills get stuck or if you're downing 18 ounces during a mealtime, maybe it's time to treat it. People don't see these coping mechanisms they use that are impacting their quality of life. They've normalized it.   [15:30] Dr. Dellon says, of these people who aren't treated, there's probably a subset who appropriately are being observed and don't have a medicine treatment or are on a diet elimination.   [15:43] There's also probably a subset who are inappropriately not on treatment. It especially can happen with students who were under good control with their pediatric provider, but moved away to college and didn't transfer to adult care.   [16:08] They ultimately come back with a lot of symptoms that have progressed over six to eight years.   [16:18] Ryan meets newly diagnosed adult patients at APFED's conferences, who say they have no symptoms, but chicken gets caught in their throat. They got diagnosed when they went to the ER with a food impaction.   [16:38] Ryan says you have to wonder at what point that starts to get reflected in patient charts. Are those cases documented where someone is untreated and now has EoE?   [16:49] Ryan asks in the study, "What is the target EGID Cohort and why was it selected to study EoE? What sort of patients were captured as part of that data set?"   [16:58] Dr. Jensen said they identified patients with the ICD-10 code for a diagnosis of EoE. Then they looked to see if there was evidence of symptoms or complications in relation to EoE. This was hard; some of these are relatively non-specific symptoms.   [17:23] These patients may have been seeking care and may have been experiencing some symptoms that may or may not have made it into the chart. That's one of the challenges with real-world data analyses.   [17:38] Dr. Jensen says they are using data that was collected for documenting clinical care and for billing for clinical care, not for research, so it comes with some caveats when doing research with this data.   [18:08] Research using electronic health records gives a real-world perspective on patients who are seeking care or have a diagnosis of EoE, as opposed to a study trying to enroll a patient population that potentially isn't representative of the breadth of individuals living with EoE.   [18:39] Dr. Dellon says another advantage of real-world data is the number of patients. The largest randomized controlled trials in EoE might have 400 patients, and they are incredibly expensive to do.   [18:52] A study of electronic health records (EHR) is reporting on the analysis of just under 1,000. The cohort, combined from three different centers, has more than 1,400 people, a more representative, larger population.    [19:16] Dr. Dellon says when you read the results, understand the limitations and strengths of a study of health records, to help contextualize the information.   [19:41] Dr. Dellon says it's always easier to recognize the typical presentations. Materials about EoE and studies he has done that led to medicine approvals have focused on trouble swallowing. That can be relatively easily measured.   [20:01] Patients often come to receive care with a food impaction, which can be impactful on life, and somewhat public, if in a restaurant or at work. Typical symptoms are also the ones that get you diagnosed and may be easier to treat.   [20:26] Dr. Dellon wonders if maybe people don't treat some of the atypical symptoms because it's not appreciated that they can be related to EoE.   [20:42] Holly was diagnosed as an adult. Ryan was diagnosed as a toddler. Holly asks what are some of the challenges people face in getting an EoE diagnosis.   [20:56] Dr. Jensen says symptoms can sometimes be fairly non-specific. There's some ongoing work by the CEGIR Consortium trying to understand what happens when patients come into the emergency department with a food bolus impaction.   [21:28] Dr. Jensen explains that we see there's quite a bit of variation in how that gets managed, and if they get a biopsy. You have to have a biopsy of the esophagus to get a diagnosis of EoE.   [21:45] If you think about the steps that need to happen to get a diagnosis of EoE, that can present barriers for some groups to ultimately get that diagnosis.   [21:56] There's also been some literature around a potential assumption about which patients are more likely to be at risk. Some of that is still ongoing. We know that EoE occurs more commonly in males in roughly a two-to-one ratio. Not exclusively in males, obviously, but a little more often in males.   [22:20] We don't know anything about other groups of patients that may be at higher risk. That's ongoing work that we're still trying to understand. That in itself can also be a barrier when there are assumptions about who is or isn't likely to have EoE.   [23:02] Dr. Dellon says that in adolescents and adults, the typical symptoms are trouble swallowing and food sticking, which have many causes besides EoE, some of which are more common.   [23:18] In that population, heartburn is common. Patients may report terrible reflux that, on questioning, sounds more like trouble swallowing than GERD. Sometimes, with EoE, you may have reflux that doesn't improve. Is it EoE, reflux, or both?   [24:05] Some people will have chest discomfort. There are some reports of worsening symptoms with exercise, which brings up cardiac questions that have to be ruled out first.   [24:19] Dr. Dellon mentions some more atypical symptoms. An adult having pain in the upper abdomen could have EoE. In children, the symptoms could be anything in the GI tract. Some women might have atypical symptoms with less trouble swallowing.   [24:58] Some racial minorities may have those kinds of symptoms, as well. If you're not thinking of the condition, it's hard to make the diagnosis.   [25:08] Dr. Jensen notes that there are different cultural norms around expressing symptoms and dietary patterns, which may make it difficult to parse out a diagnosis.   [25:27] Ryan cites a past episode where access to a GI specialist played a role in diagnosing patients with EoE. Do white males have more EoE, or are their concerns just listened to more seriously?   [25:57] Ryan's parents were told when he was two that he was throwing up for attention. He believes that these days, he'd have a much easier time convincing a doctor to listen to him. From speaking to physicians, Ryan believes access is a wide issue in the field.   [26:23] Dr. Dellon tells of working with researchers at Mayo in Arizona and the Children's Hospital of Phoenix. They have a large population of Hispanic children with EoE, much larger than has been reported elsewhere. They're working on characterizing that.   [26:49] Dr. Dellon describes an experience with a visiting trainee from Mexico City, where there was not a lot of EoE reported. The trainee went back and looked at the biopsies there, and it turned out they were not performing biopsies on patients with dysphagia in Mexico City.   [27:13] When he looked at the patients who ended up getting biopsies, they found EoE in 10% of patients. That's similar to what's reported out of centers in the developed world. As people are thinking about it more, we will see more detection of it.   [27:30] Dr. Dellon believes those kinds of papers will be out in the next couple of months, to a year.   [27:36] Holly has had licensure in Arizona for about 11 years. She has had nine referrals recently of children with EoE from Arizona. Normally, it's been one or two that she met at a conference.   [28:00] Ryan asks about the research on patients not having their EoE treated pharmacologically. Some treat it with food avoidance and dietary therapy. Ryan notes that he can't have applesauce, as it is a trigger for his EoE.   [28:54] Dr. Jensen says that's one of the challenges in using the EHR data. That kind of information is only available to the researchers through free text. That's a limitation of the study, assessing the use of dietary elimination approaches.   [29:11] Holly says some of her patients have things listed as allergies that are food sensitivities. Ryan says it's helpful for the patients to have their food sensitivities listed along with their food allergies, but it makes records more difficult to parse for research.   [30:14] Dr. Dellon says they identify EoE by billing code, but the codes are not always used accurately. Natural Language Processing can train a computer system to find important phrases. Their collaborators working on the real-world data are using it.   [30:59] Dr. Dellon hopes that this will be a future direction for this research to find anything in the text related to diet elimination.   [31:32] Dr. Jensen says that older patients were less likely to seek medication therapy. She says it's probably for a couple of reasons. First, older patients may have been living with the disease for a long time and have had compensatory mechanisms in place.   [32:03] The other reason may be senescence or burnout of the disease, long-term. Patients may be less symptomatic as they get older. That's a question that remains to be answered for EoE. It has been seen in some other disease processes.   [32:32] Dr. Dellon says there's not much data specifically looking at EoE in the older population. Dr. Dellon did work years ago with another doctor, and they found that older patients had a better response to some treatments, particularly topical steroids.   [32:54] It wasn't clear whether it was a milder aspect of the disease, easier to treat, or because they were older and more responsible, taking their medicines as prescribed, and having a better response rate. It's the flip side of work in the pediatric population.   [33:16] There is an increasingly aging population with EoE. Young EoE patients will someday be over 65. Dr. Dellon hopes there will be a cure by that point, but it's an expanding population now.   [33:38] Dr. Jensen says only a few sites are contributing data, so they hope to add additional sites to the study. For some of the less common outcomes, they need a pretty large patient sample to ask some of those kinds of questions.   [33:55] They will continue to follow up on some of the work that this abstract touched on and try to understand some of these issues more deeply.   [34:06] Dr. Dellon mentions other work within the cohort. Using Natural Language Processing, they are looking at characterizing endoscopy information and reporting it without a manual review of reports and codes. You can't get that from billing data.   [34:29] Similarly, they are trying to classify patient severity by the Index of Severity with EoE, and layer that on looking at treatments and outcomes based on disease severity. Those are a couple of other directions where this cohort is going.   [34:43] Holly mentions that this is one of many research projects Dr. Jensen and Dr. Dellon have collaborated on together. They also collaborate through EGID Partners. Holly asks them to share a little bit about that.   [34:53] Dr. Jensen says EGID Partners is an online registry where individuals, caregivers, and parents of children affected with EGIDs can join.   [35:07] EGID Partners also needs people who don't live with an EGID to join, as controls. That gives the ability to compare those who are experiencing an EGID relative to those who aren't.   [35:22] When you join EGID Partners, they provide you with a set of questionnaires to complete. Periodically, they push out a few more questionnaires.   [35:33] EGID Partners has provided some really great information about patient experience and answered questions that patients want to know about, like joint pain and symptoms outside the GI tract.   [36:04] To date, there are close to 900 participants in the registry from all over the world. As it continues to grow, it will give the ability to look at the patient experience in different geographical areas.   [36:26] Dr. Dellon says we try to have it be interactive, because it is a collaboration with patients. The Steering Committee works with APFED and other patient advocacy groups from around the world.    [36:41] The EGID Partners website shows general patient locations anonymously. It shows the breakdown of adults with the condition and caregivers of children with the condition, the symptom distribution, and the treatment distribution.   [37:03] As papers get published and abstracts are presented, EGID Partners puts them on the website. Once someone joins, they can suggest a research idea. Many of the studies they have done have come from patient suggestions.   [37:20] If there's an interesting idea for a survey, EGID Partners can push out a survey to everybody in the group and answer questions relatively quickly.   [37:57] Dr. Dellon says a paper came out recently about telehealth. EoE care, in particular, is a good model for telehealth because it can expand access for patients who don't have providers in their area.   [38:22] EoE is a condition where care involves a lot of discussion but not a lot of need for physical exams and direct contact, so telehealth can make things very efficient.    [38:52] EGID Partners surveyed patients about telehealth. They thought it was efficient and saved time, and they had the same kind of interactions as in person. In general, in-state insurance covered it. Patients were happy to do those kinds of visits again.   [39:27] Holly says Dr. Furuta, herself, and others were published in the Gastroenterology journal in 2019 about starting to do telehealth because patients coming to the Children's Hospital of Colorado from out of state had no local access to feeding therapy.   [39:50] Holly went to the board, and they allowed her to get licensure in different states. She started with some of the most impacted patients in Texas and Florida in 2011 and 2012. They collected data. They published in 2019 about telehealth's positive impact.   [40:13] When 2020 rolled around, Holly had trained a bunch of people on how to do feeding therapy via telehealth. You have to do all kinds of things, like make yourself disappear, to keep the kids engaged and in their chairs!   [40:25] Now it is Holly's primary practice. She has licenses in nine states. She sees people all over the country. With her diagnosis, her physicians at Mass General have telehealth licensure in Maine. She gets to do telehealth with them instead of driving two hours.   [40:53] Dr. Jensen tells of two of the things they hope to do at EGID Partners. One is trying to understand more about reproductive health for patients with an EGID diagnosis. Only a few studies have looked at this question, and with very small samples.   [41:15] As more people register for EGID Partners, Dr. Jensen is hoping to be able to ask some questions related to reproductive health outcomes.   [41:27] The second goal is a survey suggested by the Student Advisory Committee, asking questions related to the burden of disease specific to the teen population.   [41:48] This diagnosis can hit that population particularly hard, at a time when they are trying to build and sustain friendships and are transitioning to adult care and moving away from home. This patient population has a unique perspective we wanted to hear.   [42:11] Dr. Jensen and Dr. Dellon work on all kinds of other projects, too.   [42:22] Dr. Dellon says they have done a lot of work on the early-life factors that may predispose to EoE. They are working on a large epidemiologic study to get some insight into early-life factors, including factors that can be measured in baby teeth.   [42:42] That's outside of EGID Partners. It's been ongoing, and they're getting close, maybe over the next couple of years, to having some results.   [43:03] Ryan says all of those projects sound so interesting. We need to have you guys back to dive into those results when you have something finalized.   [43:15] For our listeners who want to learn more about eosinophilic disorders, we encourage you to visit apfed.org and check out the links in the show notes below.   [43:22] If you're looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.   [43:31] If you'd like to connect with others impacted by eosinophilic diseases, please join APFED's online community on the Inspire Network at apfed.org/connections.   [43:41] Ryan thanks Dr. Dellon and Dr. Jensen for joining us today. This was a fantastic conversation. Holly also thanks APFED's Education Partners GSK, Sanofi, Regeneron, and Takeda for supporting this episode.   Mentioned in This Episode: Evan S. Dellon, MD, MPH, Academic Gastroenterologist, University of North Carolina School of Medicine   Elizabeth T. Jensen, MPH, PhD, Epidemiologist, Wake Forest University School of Medicine, University of North Carolina at Chapel Hill   Predictors of Patients Receiving No Medication for Treatment of Eosinophilic Esophagitis in the United States: Data from the TARGET-EGIDS Cohort   Episode 15: Access to Specialty Care for Eosinophilic Esophagitis (EoE)   APFED on YouTube, Twitter, Facebook, Pinterest, Instagram Real Talk: Eosinophilic Diseases Podcast apfed.org/specialist apfed.org/connections apfed.org/research/clinical-trials   Education Partners: This episode of APFED's podcast is brought to you thanks to the support of GSK, Sanofi, Regeneron, and Takeda.   Tweetables:   "I've been working on eosinophilic gastrointestinal diseases for about 15 years. I started some of the early work around understanding possible risk factors for the development of disease. I've gone on to support lots of other research projects." — Elizabeth T. Jensen, MPH, PhD   "You can think of EoE as asthma of the esophagus or eczema of the esophagus, although in general, people don't grow out of EoE, like they might grow out of eczema or asthma. When people have it, it really is a long-term condition." — Evan S. Dellon, MD, MPH   "There are two general approaches to treating the underlying condition, … using medicines and/or eliminating foods from the diet that we think may trigger EoE. I should say, for a lot of people, EoE is a food-triggered allergic condition." — Evan S. Dellon, MD, MPH   "I didn't find it that surprising [that there are patients who had no treatment]. Some patients are relatively asymptomatic, and others are not interested in pursuing medications initially or are … still exploring dietary treatment options." — Elizabeth T. Jensen, MPH, PhD   "We have a bunch of studies now that look at how long people have symptoms before they're diagnosed. There's a wide range. Some people get symptoms and are diagnosed right away. Other people might have symptoms for 20 or 30 years." — Evan S. Dellon, MD, MPH   "EGID Partners is an online registry where individuals, caregivers, and parents of children affected with EGIDs can join. EGID Partners also needs people who don't live with an EGID to join, as controls." — Elizabeth T. Jensen, MPH, PhD

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

The best biotech and pharmaceutical innovations mean nothing if they can't be protected—and protected fast. Our next guest, Josh Goldberg, is solving this challenge as co-managing partner at Nath, Goldberg & Meyer, the #1 ranked patent law firm for biotech and pharmaceutical technologies. With nearly three decades of IP law experience and a unique background as a lab researcher, Josh brings an insider's understanding of how innovation actually happens. He's helped industry leaders like Amgen, Takeda, and GlaxoSmithKline turn breakthrough treatments into patent-protected portfolios—often in under a year instead of the typical four-year timeline. Driven by a passion for focus and strategic IP timing, Josh shares his pioneering approach to biotech and pharmaceutical patent prosecution. Join us to discover how smart IP strategy drives licensing power, regulatory success, and company valuation. Let's go!Episode Highlights:Focus drives success – Companies fail by trying to do everything at once; staying deliberate and focused is key to making real impactOne-year patent timelines vs. four years – Josh uses USPTO's Track 1 program to secure patents in record time, improving fundraising and M&A positioningClient-centered approach wins – Listening to unique client needs instead of one-size-fits-all strategies earned the firm its #1 rankingDiagnostic patents are back – New USPTO Director signals the patent office is "open for business" again after a decade of restrictionsScientist turned patent attorney – Josh's lab background gives him insider understanding of how innovation actually happensAbout our Guest: Joshua is the patent attorney innovation-driven pharmaceutical companies call when they need to turn complicated technologies into protected assets in record time.As co-managing partner at Nath, Goldberg & Meyer—the #1 ranked patent law firm for biotech and pharmaceutical technologies in both 2024 and 2025—Joshua leads IP efforts across industries like biotech, pharma, agriculture, renewable energy, and advanced materials. Whether it's a blockbuster acne treatment like DUAC, a vitamin D analog lotion like Sorilux, OTC solutions like Salonpas and Germagic, or a leading drug used to reduce stomach acid and treat conditions like GERD, ulcers, and heartburn—like Protonix—Joshua helps turn high-stakes R&D into patent-protected portfolios, often in under a year instead of the typical four-year timeline.Though his climate and agricultre IP expertise has made him famous as the “green patent guy,” Joshua moves between disciplines skillfully and has helped industry leaders like Amgen, Takeda, Guilford Pharmaceuticals, Mayne, and Stiefel Laboratories (which was acquired by GlaxoSmithKline) build pharma portfolios that hold up under investor, acquirer, and FDA scrutiny.His journey didn't begin in IP law, but in the lab, researching experimental pharmaceutical delivery systems. It gave him an edge most attorneys don't have: understanding how innovation actually happens, and how to protect it without slowing a business down. Links Supporting This Episode: Nath, Goldberg & Meyer Website: CLICK HEREJoshua Goldberg LinkedIn page: CLICK HERENath, Goldberg & Meyer LinkedIn: CLICK HEREMike Biselli LinkedIn page: CLICK HEREMike Biselli Twitter page:...

The orexin receptor agonists are coming. After years of managing narcolepsy with stimulants, sodium oxybate, and wake-promoting agents, we soon will have medications that target the root cause of the disorder: the loss of orexin signaling. These new drugs—developed by Takeda, Alkermes, and Centessa—aren't just incremental improvements. They represent a genuine shift in how we understand and treat hypersomnolence disorders. In this episode, we will:Define what orexin is and why losing it destabilizes wakefulness, REM boundaries, muscle tone, and cognitionLearn how orexin agonists work—not as stimulants, but as replacement therapy for a missing neurotransmitterFind out why OX2R is the key receptor, and how selective agonists restore stable wakefulness, reduce cataplexy, and normalize attentionReview the available clinical data from the new wave of programs: oveporexton (Takeda), alixorexton (Alkermes), and ORX750 (Centessa)See what makes these drugs different from modafinil, amphetamines, solriamfetol, and oxybate therapiesLearn why Phase 1, Phase 2, and Phase 3 trials matter—with quick insights on how these drugs reached such strong resultsConsider safety and side effects, including what Hy's Law means and why regulators watch liver signals so closelyLook ahead to what these medications may mean for NT1, NT2, IH, and other hypersomnolence disorders in the coming yearsSpeculate why this class represents one of the most exciting moments in modern sleep medicineProduced by: Maeve WinterMore Twitter: @drchriswinter IG: @drchriwinter Threads: @drchriswinter Bluesky: @drchriswinter The Sleep Solution and The Rested Child Thanks for listening and sleep well!

“If you’re not going overseas, you’re going out,” says Dr. Xingli Wang, Co-President of Fosun Pharma. He tells Bloomberg Intelligence’s Sam Fazeli how Fosun is transitioning from generics to novel medicines and positioning itself as a global innovator. With 90% of R&D now focused on oncology, autoimmune and neurodegenerative diseases, Wang details Fosun’s ambition to move from a China-based manufacturer to a multinational developer with true blockbuster potential. He also reflects on how disciplined capital investment, scientific partnerships and cultural persistence could make Fosun the “Takeda of China.”Listen to this episode of Vanguards of Health Care on Apple Podcasts and SpotifySee omnystudio.com/listener for privacy information.

Tyler and Konnery are joined by Tecate-drinking, elf-smashing companion Cameron Takeda to wrap out Guillermo del Toro's horror action duology with "Hellboy II: The Golden Army"! Together they discuss Guillermo's post Pan's Labyrinth acclaim, the incredible creature and set designs, this second film's strength at standing on its own story, dive deep into each other's histories with comic books, and so much more on this Barry Manilow-sing-along episode of The Friendchise Podcast! What's New: Konnery: Dungeon Crawler Carl Book: The Butcher's Masquerade by Matt Dinniman Tyler: Chapterhouse Dune by Frank Herbert (Libby), Perfect Blue (4K Restoration In Theaters) Cameron: Megazone 23 and Megazone 23 Pt II (Prime Video, Tubi)

This accredited continuing education program is supported by an educational grant from Sanofi. Credit for the program can be obtained by visiting https://checkrare.com/learning/p-consider-rare-suspecting-and-diagnosing-cidp/ . This program, led by Jeffrey Allen, MD, Professor of Neurology at the University of Minnesota provides an overview on the diagnostic delays that often occur in patients with CIDP as well as best practices to suspect and diagnose this rare condition more efficiently. This activity has been designed to meet the educational needs of physicians specializing in family medicine, pediatrics, and neurology. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the early symptoms of CIDP.List best practices which can be used to diagnose CIDP more efficiently.Faculty Jeffrey Allen, MDProfessor of NeurologyDepartment of NeurologyDivision of Neuromuscular MedicineUniversity of MinnesotaMinneapolis, MNDisclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Scott discloses Consultant/Educational talks: Annexon, Alexion, Amgen, CSL Behring, Takeda,BioCryst, Grifols, Argenx, Sanofi, Immunovant, ImmunoAbs, Octapharma, Alnylam, AstraZeneca, Dianthus, Johnson & Johnson, Laboratoire Français du Fractionnement et des Biotechnologies, Nuvig, Akcea Therapeutics, ImmunoPharma,Pfizer.Community Faculty/Patient (Christine Eleeson): No relevant financial relationships with any ineligible companies.Other Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre-and post-program assessments. Your certificate will be emailed to you within 30 days.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Synopsis: Nimbus Therapeutics CEO Abbas Kazimi walks Alok Tayi through the company's evolving pipeline and playbook for choosing the right risks in a noisy biotech environment. From Werner helicase for MSI-high cancers to a highly selective SIK2 program and GLP-1–adjacent strategies focused on body composition, Abbas details how Nimbus balances rigor, speed, and capital efficiency. He shares candid lessons from pausing and later resurrecting AMPK beta in partnership with Eli Lilly, the decision to remain modality-agnostic but small-molecule-centric, and the importance of knowing when not to chase the latest fad. Throughout, Abbas returns to a consistent theme: success at Nimbus comes from disciplined target selection, deep collaboration, and a culture that empowers teams to make hard calls in service of patients rather than headlines. Biography: Abbas Kazimi is the Chief Executive Officer of Nimbus Therapeutics. Previously, he served as Chief Business Officer, leading the company's strategic and corporate development efforts while overseeing business operations. Since joining Nimbus in 2014, he has helped raise over $630 million in equity financing and led transactions totaling more than $8 billion. Notably, Mr. Kazimi spearheaded the $6 billion sale of Nimbus's TYK2 program to Takeda, the $1.2 billion sale of its NASH (ACC) program to Gilead, and multiple licensing deals exceeding $1.5 billion with partners such as Genentech, Celgene/Roche, and Eli Lilly. Under his leadership, Nimbus has advanced four programs into the clinic, returned over $4 billion to investors, and continues to expand its computational drug discovery and clinical development capabilities. In 2025, Mr. Kazimi joined the board of Unnatural Products (UNP), a biotech company pioneering orally delivered macrocyclic peptides to tackle previously undruggable targets. He also serves on the Editorial Advisory Board for In Vivo magazine, a leading publication offering strategic insights and analysis of the pharmaceutical, biotechnology, medtech, and consumer health industries. Along with his family, he established the Kazimi Family Endowment for Data Science in Oncology at MD Anderson Cancer Center. This endowment reflects their personal commitment to philanthropy and their vision for revolutionizing cancer treatment through data-driven innovation. At the core of Mr. Kazimi's leadership is a deep sense of purpose—one that seeks to change the trajectory of medical diagnoses where options are limited. The ability to give patients, prescribers, and families a new outlook on life is a powerful responsibility—and one he knows the biopharmaceutical sector has the ability to fulfill. Before Nimbus, he was at Extera Partners, LLC (formerly PureTech Development, LLC), where he provided strategic advisory, supported fundraising, and executed numerous business development transactions. Earlier in his career, he was with JSB-Partners, LP, a specialized investment banking and advisory firm serving biotech and pharmaceutical companies. Mr. Kazimi holds a B.A. from the University of Texas at Austin and an M.S. from Harvard University.

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

In this episode of PNC C-Speak, Christophe Weber, president and CEO of Takeda Pharmaceuticals, discusses the company's global footprint and its mission to deliver life-transforming medicines worldwide.  Weber shares his leadership perspective, emphasizing the importance of cultural agility and value-driven operations.  “Our mission is to deliver life-transforming medicines. When we develop new medicines —  which is a very hard mission — we really aim for that medicine to be made available across the world for all patients,” Weber says. Listen to hear more about:-              Takeda's approach to ‘caring leadership' (4:33)-              How Takeda's corporate social responsibility program unites all employees (8:46)-              Where Takeda believes AI can make a difference (12:10)-              Why Takeda moved its headquarters to Massachusetts (15:00)Download a transcript of this episode.

This episode covers: Cardiology this Week: A concise summary of recent studies Lp(a) - What to expect in the very near future Myocardial infarction in older and frail adults Mythbusters: is beetroot good for your heart? Host: Rick Grobbee Guests: JP Carpenter, Vijay Kunadian, Erik Stroes Want to watch that episode? Go to: https://esc365.escardio.org/event/2177 Want to watch that extended interview on Lp(a), go to: https://esc365.escardio.org/event/2177?resource=interview   Disclaimer  ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails.    Declarations of interests Stephan Achenbach, Yasmina Bououdina, Rick Grobbee, Nicolle Kraenkel, Vijay Kunadian and Erik Stroes have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder MyCardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

China is setting a new bar for the speed of clinical development and redefining the time it takes an asset to get to the clinic. On a special edition of the BioCentury This Week podcast recorded on stage at the 12th BioCentury BayHelix China Healthcare Summit in Shanghai, BioCentury's Simone Fishburn argued that China's emerging new standard for swift entry to the clinic could upend the bottleneck of translational development and usher in a new paradigm that could have a “massive impact globally.”Fishburn and her BioCentury colleagues Joshua Berlin and Jeff Cranmer were joined by a trio of cross-border KOLs — John Zhu, CEO of antibody-drug conjugate company DualityBio; Matt Hewitt, CTO of  Charles River Laboratories' manufacturing business division; and Bing Wang, CFO of Akeso — to discuss the speed of generating first-in-human data, Innovent's $1.2 billion deal with Takeda, an evolving biotech talent pool, and the state of the financial markets.“For me, it really feels like 2025 is the year that biotech globally woke up to China,” Fishburn said.BioCentury returns to Asia early next year for the 5th East-West Summit, March 9-11 in Seoul. Register today as a delegate or apply to join the Presenting Company Class to take advantage of early bird rates.#ChinaInnovation #DrugDevelopment #PharmaDeals #GlobalBiotech #PharmaInnovation #siRNA #BrainToVein00:00 - Introduction02:49 - China Speed12:27 - Clinical Trails 17:34 - Global Strategy26:59 - Financial Markets IPOs36:52 - TalentTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Co-hosts Ryan Piansky, a graduate student and patient advocate living with eosinophilic esophagitis (EoE) and eosinophilic asthma, and Holly Knotowicz, a speech-language pathologist living with EoE who serves on APFED's Health Sciences Advisory Council, interview Dr. Andrew Lee, Vice President, Clinical Research at Uniquity Bio, about Thymic Stromal Lymphopoietin (TSLP) and eosinophilic esophagitis (EOE). Disclaimer: The information provided in this podcast is designed to support, not replace, the relationship between listeners and their healthcare providers. Opinions, information, and recommendations shared in this podcast are not a substitute for medical advice. Decisions related to medical care should be made with your healthcare provider. Opinions and views of guests and co-hosts are their own.   Key Takeaways: [:49] Co-host Ryan Piansky introduces the episode, brought to you thanks to the support of Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda. Ryan introduces co-host Holly Knotowicz.   [1:13] Holly introduces today's topic, Thymic Stromal Lymphopoietin (TSLP) and eosinophilic esophagitis (EOE), and today's guest, Dr. Andrew Lee, Vice President, Clinical Research at Uniquity Bio.   [1:36] Dr. Lee has nearly 20 years of experience in the clinical development of new vaccines, biologics, and drugs. Holly welcomes Dr. Lee.   [1:52] Dr. Lee trained in internal medicine and infectious diseases.   [1:58] Dr. Lee has been fascinated by the immune system and how it can protect people against infections, what happens when immunity is damaged, as in HIV and AIDS, and how to apply that knowledge to boost immunity with vaccines to prevent infections.   [2:16] Dr. Lee led the clinical development for a pediatric combination vaccine for infants and toddlers. It is approved in the U.S. and the EU.   [2:29] Dr. Lee led the Phase 3 Program for a monoclonal antibody to prevent RSV, a serious infection in infants. That antibody was approved in June 2025 for use in the U.S.   [2:44] In his current company, Dr. Lee leads research into approaches to counteract an overactive immune system. They're looking at anti-inflammatory approaches to diseases like asthma, EoE, and COPD.   [2:58] Dr. Lee directs the ongoing Phase 2 studies that they are running in those areas.   [3:28] Dr. Lee sees drug development as a chance to apply cutting-edge research to benefit people. He trained at Bellevue Hospital in New York City in the 1990s.   [3:40] When Dr. Lee started as an intern, there were dedicated ICU wards for AIDS patients because many of the sickest patients were dying of AIDS and its complications.    [3:52] Before the end of Dr. Lee's residency, they shut down those wards because the patients were on anti-retroviral medications and were doing so well that they were treated as outpatients. They didn't need dedicated ICUs for AIDS patients anymore.   [4:09] For Dr. Lee, that was a powerful example of how pharmaceutical research and drug regimen can impact patients' lives for the better by following the science. That's what drove Dr. Lee to go in the direction of research.   [4:48] Dr. Lee explains Thymic Stromal Lymphopoietin (TSLP). TSLP serves as an alarm signal for Type 2 or TH2 inflammation, a branch of the immune responses responsible for allergic responses and also immunity against parasites.   [5:17] When the cells that line the GI tract and the cells that line the airways in our lungs receive an insult or an injury, they get a danger signal, then they make TSLP.   [5:28] This signal activates other immune cells, like eosinophils and dendritic cells, which make other inflammatory signals or cytokines like IL-4, IL-13, and IL-5.   [5:47] That cascade leads to inflammation, which is designed to protect the body in response to the danger signal, but in some diseases, when there's continued exposure to allergens or irritants, that inflammation goes from being protective to being harmful.   [6:15] That continued inflammation, over the years, can lead to things like the thickened esophagus with EoE, or lungs that are less pliant and less able to expand, in respiratory diseases.   [6:48] Dr. Lee says he thinks of TSLP as being a master switch for this branch of immune responses. If you turn on TSLP, that turns on a lot of steps that lead to generating an allergic type of response.   [7:06] It's also the same type of immune response that can fight off parasite infections. It's the first step in a cascade of other steps generating that type of immune response.   [7:30] Dr. Lee says people have natural genetic variation in the genes that incur TSLP.   [7:38] Observational studies have found that some people with genetic variations that lead to higher levels of TSLP in their bodies had an increased risk for allergic inflammatory diseases like EoE, atopic dermatitis, and asthma.   [8:13] Studies like the one just mentioned point to TSLP being important for increased risk of developing atopic types of diseases like EoE and others. There's been some work done in the laboratory that shows that TSLP is important for activating eosinophils.    [8:38] There's accumulating evidence that TSLP activation leads to eosinophil activation, other immune cells, or white blood cells getting activated.   [9:07] Like a cascade, those cells turn on T-cells and B-cells, which are like vector cells. They lead to direct responses to fight off infections, in case that's the signal that leads to the turning on TSLP.   [9:48] Ryan refers to a paper published in the American Journal of Gastroenterology exploring the role of TSLP in an experimental mouse model of eosinophilic esophagitis. Ryan asks what the researchers were aiming to find.   [10:00] Dr. Lee says the researchers were looking at the genetic studies we talked about, the observational studies that are beginning to link more TSLP with more risk for EoE and those types of diseases.   [10:12] The other type of evidence that's accumulating is from in vitro (in glass) experiments or test tube experiments, where you take a couple of cells that you think are relevant to what's going on.   [10:28] For example, you could get some esophageal cells and a couple of immune cells, and put TSLP into the mix, and you see that TSLP leads to activation of those immune cells and that leads to some effects on the esophageal cells.   [10:42] Those are nice studies, but they're very simplified compared to what you can do in the body. These researchers were interested in extending those initial observations from other studies, but working in the more realistic situation of a mouse model.   [11:00] You have the whole body of the mouse being involved. You can explore what TSLP is doing and model a disease that closely mimics what's happening with EoE in humans.   [12:23] They recreated the situation of what seems to be happening in EoE in people. We haven't identified it specifically, but there's some sort of food allergen in patients with EoE that the immune system is set off by.   [12:55] What researchers are observing in this paper is that in these mice that were treated with oxazolone, there is inflammation in the esophagus, an increase in TSLP levels, and eosinophils going into the esophageal tissues.   [13:15] Dr. Lee says, that's one of the main ways we diagnose EoE; we take a biopsy of the esophagus and count how many eosinophils there are. Researchers saw similar findings. The eosinophil count in the esophageal tissues went way up in these mice.    [13:34] Researchers also saw other findings in these mice that are very similar to EoE in humans, such as the esophageal cells lining the esophagus proliferating. They even saw that new blood vessels were being created in that tissue that's getting inflamed.   [14:00] Dr. Lee thinks it's a very nice paper because it shows that correlation: Increase TSLP and you see these eosinophils going to the esophagus, and these changes that are very reminiscent of what we see in people with EoE.   [14:51] In this paper, the mice made the TSLP, and researchers were able to measure the TSLP in the esophageal tissue. The researchers didn't introduce TSLP into the mice. The mice made the TSLP in response to being repeatedly exposed to oxazolone.   [15:20] That's key to the importance of the laboratory work. The fact that the TSLP is made by the mice is important. It makes it a very realistic model for what we're seeing in people.   [15:41] In science, we like to see correlation. The researchers showed a nice correlation.   [15:46] When TSLP went up in these mice, and the mice were making more TSLP on their own, at the same time, they saw all these changes in the esophagus that look a lot like what EoE looks like in people.    [16:01] They saw the eosinophils coming into the esophagus. They saw the inflammation go up in the esophagus. What Dr. Lee liked about this paper is that they continued the story.   [16:15] The researchers took something that decreases TSLP levels, an antibody that binds to and blocks TSLP, and when they did that, they saw the TSLP levels come down to half the peak level.   [16:35] Then they saw improvement in the inflammation in the esophagus. They saw that the amount of eosinophils decreased, and the multiplication of the esophageal cells went down. The number of new blood vessels went down after the TSLP was reduced.   [16:53] Dr. Lee says, you see correlation. The second part is evidence for causation. When you take TSLP away, things get better. That gives us a lot of confidence that this is a real finding. It's not just observational. There is causation evidence here.   [18:26] Ryan asks if cutting TSLP also help reduce other immune response cells. Dr. Lee says TSLP is the master regulator for this Type 2 inflammation. It definitely touches and influences other cells besides eosinophils.   [18:44] TSLP affects dendritic cells, which are an important type of immune cell, like a coordinating cell that instructs other cells within the immune system what to do. In this paper, they looked at a lot of other effects of TSLP on the tissues of the body.   [19:10] Dr. Lee says, There's a lot of research on TSLP, and one of the reasons we're excited about the promise of TSLP is that it's so far upstream; so much of the beginning, that it's affecting other cells.   [19:29] Its effects could be quite broad. If we're able to successfully block TSLP, we could block a lot of different effects.   [19:40] One treatment for EoE is dupilumab, which blocks IL-4 and IL-13 specifically, and that works well, but TSLP has the potential to have an even greater effect than blocking IL-4 and IL-13, since it is one step before turning on IL-4 and IL-13.    [20:14] That's one of the reasons researchers are excited about the promise of blocking TSLP. There are studies ongoing of TSLP blockers in people with EoE.   [20:34] Ryan asks if there are negative repercussions from blocking TSLP. Dr. Lee says in this study and in people, we are not completely blocking TSLP by any means. There will still be residual TSLP activated, even with very potent drugs.   [21:01] In the study, they block TSLP about 50%‒60%. TSLP is involved in immunity against parasites. In studies with people, they make sure not to include anybody who has an active parasitic infection. A person under treatment should not be in a study.   [21:27] Dr. Lee says we haven't seen any problems with parasitic infections becoming more severe, but that is a theoretical possibility, so for that reason, in studies with TSLP blockers, we generally exclude patients with known parasitic infections.   [22:17] What excited Dr. Lee in this paper was that they showed that when you block TSLP in the mice, then you get real effects in their tissues. Eosinophils went away. The thickening of the basal layers in the esophagus got much better.   [22:38] That kind of real effect reflected in the tissue is super exciting to see. That gives us more confidence that this could work in people, since we're seeing it in a realistic whole-body model in the mice.   [23:12] Dr. Lee says there are ongoing clinical studies on TSLP blockers for EoE. His company is studying an antibody that blocks TSLP in eczema, COPD, and EoE. One of the exciting things about immunology is that it affects many different parts of the body.   [23:42] EoE is associated with other immune-type disorders. There's a high percentage of patients with EoE who have other diseases. EoE coexists with asthma, atopic dermatitis, and chronic rhinitis.   [24:09] It's exciting that if you figure out something that's promising for one disease that TSLP affects, it could have very broad-ranging implications for a variety of diseases.   [24:22] Ryan shares his experience of his doctor talking to him about a TSLP blocker, tezepelumab, as a potential option when it's out of clinical trials. It would target something a little higher up the chain and help with some of his remaining symptoms.   [24:59] Ryan is excited to hear that this research is so encouraging and how it could potentially help treat EoE, asthma, and other conditions, all at once.   [25:16] Dr. Lee says that being in these later-stage studies is super exciting. If these late-stage trials are successful, the next step is to apply for regulatory approval with the various agencies around the world.   [26:40] Dr. Lee shares one takeaway for listeners to remember. Think of TSLP as an alarm that turns on inflammation. He compares TSLP to turning on an alarm during a robbery. There are multiple steps designed to protect the bank and the money.   [27:20] To extend that analogy, with TSLP, once you turn it on, all these other steps are going to happen. Inflammation is designed to protect the body. It's a protective response. If there's an infection, it can clear the infection.   [27:38] If the infection persists, as in HIV, the immune response, which is protective and beneficial, eventually becomes damaging. It becomes dysfunctional. In EoE, if you continually eat the allergic food, the inflammation becomes damaging to the esophagus.   [28:27] Long-term inflammation leads to replacing the normal esophageal tissue with fibrotic tissue, and that's why the esophagus eventually gets hardened and less able to let the food go through.   [28:40] In respiratory diseases, the soft tissue of the lung gets replaced with thicker tissue, and the lung is not able to expand.   [28:54] Dr. Lee says he people to think about TSLP as this master alarm switch. We hope that if you could turn off that TSLP, you could then avoid a lot of the complications that we see with chronic inflammation in these conditions.   [29:14] We're hopeful that you could even take away the symptoms that you see in these diseases, make patients feel better, and with extended treatment, you could begin to reverse some of the damage resulting from inflammation.   [29:32] Ryan likes that analogy and how Dr. Lee has concisely explained these complicated concepts.   [29:51] Dr. Lee thanks Holly and Ryan and adds one more plea to listeners. Please consider getting involved with research. Clinical trials cannot be done without patients. We need patients to advance new treatments.   [30:27] Researchers like Dr. Lee spend a lot of time thinking about how to make the studies not only informative but also fair to patients who decide to become involved. It's a lot of work and a fair amount of time commitment.   [30:44] If you don't want to be in a study, you can help by being on a patient feedback panel and reviewing protocols and informed consents. Follow your interests. Think about getting involved with research, however you can.   [31:06] Ryan and Holly are very grateful for the community, with so many wonderful clinicians and researchers, and so many patients who are willing to volunteer their time and their data to help researchers find better solutions going forward.   [31:26] Ryan thanks Dr. Lee for coming on and putting out that call to action. It's a great reminder for listeners and the patients in the community to look for those opportunities. Chat with your physician. Go to APFED's website. There's a link to active clinical trials.   [31:47] For our listeners who want to learn more about eosinophilic disorders, we encourage you to visit apfed.org and check out the links in the show notes below.   [31:53] For those looking to find specialists who treat eosinophilic disorders, we encourage you to use APFED's Specialist Finder at apfed.org/specialist.   [32:01] If you'd like to connect with others impacted by eosinophilic diseases, please join APFED's online community on the Inspire Network at apfed.org/connections.   [32:11] Ryan thanks Dr. Andrew Lee for joining us today. We learned a lot. Holly also thanks APFED's Education Partners Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda for supporting this episode.   Mentioned in This Episode: Andrew Lee, M.D., VP Clinical Research, Uniquity Bio   "A Mouse Model for Eosinophilic Esophagitis (EoE)" Current Protocols, Wiley Online Library   APFED on YouTube, Twitter, Facebook, Pinterest, Instagram Real Talk: Eosinophilic Diseases Podcast apfed.org/specialist apfed.org/connections apfed.org/research/clinical-trials   Education Partners: This episode of APFED's podcast is brought to you thanks to the support of Bristol Myers Squibb, GSK, Sanofi, Regeneron, and Takeda.   Tweetables:   "I see drug development as a chance to apply cutting-edge research to benefit people." — Andrew Lee, M.D.   "When the cells that line the GI tract and the cells that line the airways in our lungs receive an insult or an injury, they get a danger signal, then they make TSLP." — Andrew Lee, M.D.   "Observational studies have found that some people with genetic variations that lead to higher levels of TSLP in their bodies had an increased risk for allergic inflammatory diseases like EoE, atopic dermatitis, and asthma." — Andrew Lee, M.D.   "There's a lot of research on TSLP, and one of the reasons we're excited about the promise of TSLP is that it's so far upstream; so much of the beginning, that it's affecting other cells." — Andrew Lee, M.D.   "Please consider getting involved with research. We can't do these clinical trials without patients. We need patients to advance new treatments for patients." — Andrew Lee, M.D.

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

Keizo Takemi, recent Japan Minister of Health, Labour and Welfare (September 2023-October 2024), shares his personal story that took him to Taiwan, CNN/Japan, the Diet, Harvard, back to the Diet, and recently into the cabinet of then Prime Minister Kishida. Along the way he became a leading force in charting Japan's approach to global health. As Minister he put a spotlight on the thousands of single, isolated elderly who die alone in Japan, unnoticed for days. Though expensive, wearable digital technologies can help connect the elderly better to community health services. Covid-19 exposed the lack of digitalized data and the need for a national mechanism to integrate patient and hospital data. That became a priority for him as Minister, as well as the creation of the Japan Institute of Health Security, a merger that promises far greater capabilities in preparing for and responding to dangerous outbreaks. By 2035, Japan will have 10 million citizens above 85 years of age. "Speedy aging" is raising demands for different care, at considerable expense. Achieving a stable number of skilled caregivers requires better wages and work conditions, and the entry of far more migrants into the workforce. Japan's biopharmaceutical industry requires a wholistic industrial policy. That sector is hollowing out, as Takeda and Astellas locate their operations in the United States.

This episode covers: Cardiology This Week: A concise summary of recent studies Arrhythmias in cardiac amyloidosis Taking the 'O' out of HOCM: managing LVOT obstruction Snapshots Host: Susanna Price Guests: Carlos Aguiar, Stephanie Schwarting, Ahmad Masri Want to watch that episode? Go to: https://esc365.escardio.org/event/2176 Want to watch that extended interview on Arrhythmias in Cardiac Amyloidosis? Go to: https://esc365.escardio.org/event/2176?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Ahmad Masri has declared to have potential conflicts of interest to report: research grants from Pfizer, Ionis, Attralus, Cytokinetics and Janssen. Consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, Neurimmune, and Tenaya. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Stephanie Schwarting has declared to have potential conflicts of interest to report: advisory board for Alnylam, Bayer, Pfizer; principal investigator in trials sponsored by Alexion, Novo Nordisk and Intellia. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Host: Susanna Price Guest: Stephanie Schwarting Want to watch the episode? Go to: https://esc365.escardio.org/event/2176 Want to watch the extended interview on Arrhythmias in Cardiac Amyloidosis? Go to: https://esc365.escardio.org/event/2176?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis through an independent funding. The programme has not been influenced in any way by its funding partners. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests:  Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada.  Stephanie Schwarting has declared to have potential conflicts of interest to report: advisory board for Alnylam, Bayer, Pfizer; principal investigator in trials sponsored by Alexion, Novo Nordisk and Intellia. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of pivotal changes and innovations shaping the industry landscape.Let's begin with a significant acquisition that is resonating across the sector. Alkermes has strategically acquired Avadel Pharmaceuticals for a noteworthy $2.1 billion. This acquisition is primarily aimed at Avadel's long-acting narcolepsy drug, Lumryz. This move not only acts as a growth catalyst for Alkermes but also strategically positions the company to potentially advance its own narcolepsy candidate, Alixorexton. This acquisition highlights a broader trend within the industry: a shift towards consolidation and specialization in niche therapeutic areas, reflecting the ongoing strategic maneuvering within the pharmaceutical sector to enhance therapeutic portfolios.In regulatory developments, there is an ongoing discussion around FDA cancer drug policies that's gaining attention. Eli Lilly's Oncology President has highlighted the need for clearer regulatory pathways. The debate revolves around whether to prioritize survival metrics without crossover incentives or encourage U.S. participation through crossover designs. This underscores a tension between maintaining regulatory rigor and offering flexibility in clinical trial design—a balance that impacts how quickly new oncology therapies can reach patients.Turning to international trade, there are significant movements as the Trump administration initiates a probe under Section 301 of the Trade Act of 1974. The aim is to assess if foreign nations are contributing their fair share to drug costs. Such an investigation could lead to tariffs, potentially altering global pharmaceutical trade dynamics and influencing international pricing strategies. Reports suggest that former President Donald Trump is exploring strategies to impose tariffs on U.S. trading partners not adequately compensating for pharmaceuticals, reflecting ongoing tensions regarding international drug pricing.Technology is revolutionizing life sciences commercialization strategies, with AI playing a pivotal role. Despite many organizations not being fully prepared for this digital shift, companies like Real Chemistry are pioneering AI applications to navigate regulatory complexities such as FDA marketing compliance. This digital transformation is set to redefine how pharmaceutical companies engage with patients and healthcare providers, enhancing efficiency and compliance.In legal news, Regeneron has settled a patent dispute with Celltrion over Eylea, allowing for the launch of a biosimilar by the end of 2026. This settlement is part of the growing biosimilars market, which offers cost-effective alternatives to high-priced biologics and enhances patient access to essential therapies.The industry's focus on oncology is further exemplified by Takeda's $1.2 billion upfront payment to Innovent Biologics for cancer assets. This deal includes substantial milestone payments, marking oncology as a key growth area post-Entyvio era and highlighting the high stakes associated with breakthrough cancer therapies. Continuing with significant industry maneuvers, Takeda Pharmaceuticals has announced a potential investment up to $11.4 billion to acquire three antibody-drug conjugates from Innovent Biologics. This deal includes an upfront payment of $1.2 billion and up to $10.2 billion in milestone payments—highlighting Takeda's commitment to expanding its oncology portfolio with innovative therapies that promise enhanced treatment outcomes for cancer patients.Ipsen's acquisition of ImCheck Therapeutics for $1.6 billion further emphasizes this focus on novel cancer treatments. The move includes ImCheck's mid-stage leukemia monoclonal antibody ICT01—an asset aimed at acute myeloid leukemia—indicating Ipsen's strategic push intSupport the show

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we explore the rapidly evolving landscape of the pharmaceutical and biotech sectors, where regulatory updates, strategic mergers, and scientific breakthroughs are continually reshaping the industry.Starting with Novo Nordisk's recent challenges, their newly acquired manufacturing facility in Indiana has been flagged by the FDA with an "Official Action Indicated" designation. This classification, being the most severe level of inspection categorization, potentially signals delays in production and collaboration with partners like Regeneron and Scholar Rock. Such regulatory hurdles underscore the vital importance of compliance in ensuring smooth supply chains and market availability of therapeutics. It's a stark reminder of how critical regulatory oversight is in maintaining quality assurance within pharmaceutical manufacturing.Meanwhile, Johnson & Johnson is navigating its own regulatory landscape by engaging with the Trump administration on drug pricing reforms. These discussions highlight the broader industry's ongoing efforts to adapt to evolving regulatory frameworks and market dynamics. By spinning off its orthopedics unit, J&J aims to sharpen its focus and drive growth in more strategic areas, illustrating a trend towards specialization as companies strive to align with market demands.In mergers and acquisitions news, BioCryst Pharmaceuticals has completed a significant $700 million acquisition of Astria Therapeutics. This move positions BioCryst to compete directly with Takeda's hereditary angioedema therapy, Takhzyro. The acquisition emphasizes the competitive nature of specialty markets and highlights how targeted acquisitions can expand therapeutic pipelines.Halozyme Therapeutics is similarly active in pursuing mergers and acquisitions to enhance its drug delivery capabilities. Their recent acquisition of Elektrofi aligns with Halozyme's strategy to innovate in drug delivery technologies, which are increasingly recognized for their role in improving therapeutic efficacy and patient experience.Funding models are also evolving within the industry as alternative programs for specialty drugs gain attention for their potential cost-saving benefits for self-insured employers. However, these models raise ethical concerns due to potential financial risks shifting onto patients. This ongoing debate underscores the complexity of balancing cost management with patient access in healthcare.BioNTech's initiative to establish mRNA vaccine production facilities in Africa represents a significant step towards enhancing vaccine accessibility and equity on a global scale. Supported by European Union funding, this move underscores the importance of regional manufacturing hubs in facilitating rapid distribution of life-saving vaccines.Turning our focus to clinical advancements, Roche and Eli Lilly's collaboration has led to FDA approval of an Alzheimer's blood test for primary care use. This diagnostic tool could significantly enhance the adoption of Alzheimer's treatments like Biogen's Leqembi by streamlining diagnosis processes in primary care settings.Novo Nordisk's Indiana facility has again made headlines due to FDA scrutiny, potentially impacting partnerships with major players such as Regeneron. This situation highlights how stringent compliance requirements can influence strategic partnerships and operational timelines.On a promising note, Kailera Therapeutics has raised $600 million in funding to advance its obesity treatment program into Phase 3 trials. With Bain Capital leading this round, it reflects investor confidence in targeting metabolic disorders—a growing area of focus given their widespread health implications.Artificial intelligence continues to reshape drug discovery processes. Takeda Pharmaceuticals' $1 Support the show

Ozlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Raphael Schiffmann, MD, of the Texas Christian University, discuss best practices to identify and treat neurologic problems associated with lysosomal disorders.This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. To complete the program and obtain credit, visit https://checkrare.com/learning/p-lysosomal-disorders-and-the-brain/ Support for this educational activity provided by Takeda and Ultragenyx.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the role of the neurologist in the team approach to careList best practices to assess neurologic and cognitive involvement  in persons with LDsCite best practices to assess developmental delay and regression in pediatric patients with suspected LDsDescribe the latest clinical research to improve central outcomes in persons with LDs and central nervous system involvementFacultyOzlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC), Fairfax, VA Raphael Schiffmann, MDTexas Christian University,Fort Worth, TXDisclosuresAffinityCE staff, LDRTC staff, planners, and reviewers, have no relevant financial relationships with ineligible companies to disclose. Faculty disclosures, listed below, will also be disclosed at the beginning of the Program.Ozlem Goker-Alpan MDDr. Goker-Alpan is on the Advisory Board/Consultant for Chiesi, Takeda, Sanofi, Prevail/Lilly, Sparks Therapeutics, Uniqure, Exegenesis, Astellas, Freeline, Team Sanfilippo. She receives grants/research support from Chiesi, Sanofi, Takeda, Prevail/Lilly, Spark Therapeutics, Amicus, Freeline, Sangamo, Cyclo, Odorsia, $DMT, Homology, Protaliz. She is on the speaker bureau for Sanofi, Takeda, Amicus, Chiesi.Raphael Schiffman, MDDr. Schiffmann is consultant for Amicus Therapeutics, Protalix Biotherapeutics, Chiesi Farmaceutici and 4D Molecular TherapeuticsMitigation of Relevant Financial RelationshipsAffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. Conflicts of interest for presenting faculty with relevant financial interests were resolved through peer review of content by a non-conflicted reviewer. PhysiciansThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Physician AssistantsThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physician Assistants should claim only the credit commensurate with the extent of their participation in the activity.NursesContinuing Nursing Education is provided for this program through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation (ANCC). This activity provides a maximum of 1 hours of continuing nursing education credit.Nurse PractitionersThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.Genetic CounselorsCategory 2 CEUThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credit™. Genetic counselors should claim only the credit commensurate with the extent of their participation in the activity.CME InquiriesFor all CME policy-related inquiries, please contact us at mailto:ce@affinityced.comSend customer support requests to mailto:cds_support+ldrtc@affinityced.comCopyright© 2025. This CME-certified activity is held as copyrighted © by Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) and AffinityCE. Through this notice, Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) and AffinityCE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

Host: Susanna Price Guest: Rudolf de Boer Want to watch that extended interview on AI in echocardiography? Go to: https://esc365.escardio.org/event/2175?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors.  This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Rudolf de Boer has declared to have potential conflicts of interest to report: the institution of Rudolf de Boer has received research grants and/or fees from Alnylam, AstraZeneca, Abbott, Bristol-Myers Squibb, NovoNordisk, and Roche; Rudolf de Boer has had speaker engagements with and/or received fees from and/or served on an advisory board for Abbott, AstraZeneca, Bristol Myers Squibb, NovoNordisk, Roche, and Zoll; Rudolf de Boer received travel support from Abbott and NovoNordisk. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers: Cardiology This Week: A concise summary of recent studies Visceral adiposity: paradigm shift in HFpEF management Artificial Intelligence in echocardiography Milestones: ISIS-2 Host: Susanna Price Guests: Carlos Aguiar, Milton Packer, Rudolf de Boer Want to watch the episode? Go to: https://esc365.escardio.org/event/2175 Want to watch the extended interview on AI in echocardiography? Go to: https://esc365.escardio.org/event/2175?resource=interview Disclaimer: ESC TV Today is supported by Bristol Myers Squibb and Novartis. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsors. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. The ESC is not liable for any translated content of this video. The English language always prevails. Declarations of interests: Stephan Achenbach, Yasmina Bououdina, Nicolle Kraenkel and Susanna Price have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. John-Paul Carpenter has declared to have potential conflicts of interest to report: stockholder Mycardium AI. Davide Capodanno has declared to have potential conflicts of interest to report: Bristol Myers Squibb, Daiichi Sankyo, Sanofi Aventis, Novo Nordisk, Terumo. Rudolf de Boer has declared to have potential conflicts of interest to report: the institution of Rudolf de Boer has received research grants and/or fees from Alnylam, AstraZeneca, Abbott, Bristol-Myers Squibb, NovoNordisk, and Roche; Rudolf de Boer has had speaker engagements with and/or received fees from and/or served on an advisory board for Abbott, AstraZeneca, Bristol Myers Squibb, NovoNordisk, Roche, and Zoll; Rudolf de Boer received travel support from Abbott and NovoNordisk. Konstantinos Koskinas has declared to have potential conflicts of interest to report: honoraria from MSD, Daiichi Sankyo, Sanofi. Milton Packer has declared to have potential conflicts of interest to report: 89bio, Abbvie, Actavis, Altimmune, Alnylam, Amarin, Amgen, Ardelyx, ARMGO, AstraZeneca, Attralus, Biopeutics, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Daiichi Sankyo, Imara, Lilly, Medtronic, Moderna, Novartis, NovoNordisk, Pharmacocosmos, Regeneron, Roche, Salamandra. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc. Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Zenas has made a $2 billion bet on autoimmune diseases with Chinese firm InnoCare, focusing on the development of orelabrutinib for multiple sclerosis. Former FDA director Peter Marks has joined Eli Lilly, marking the company's continued push in China. Sanofi's advancements in radiopharma, Boehringer Ingelheim's breakthrough in idiopathic pulmonary fibrosis, and Takeda's exit from cell therapy are also top stories. Cytiva filtration is highlighted as a solution for maintaining product integrity in biopharma.Biospace profiles the five most powerful women leading smaller biopharmaceutical companies, as the industry sees a shift with the departure of GSK CEO Emma Walmsley. A survey by CRB reveals that most life sciences companies are not planning new investments after tariffs, with big pharma taking the lead in manufacturing initiatives. Drug pricing criticism often overlooks the dynamic nature of drug pricing over time. Takeda's journey in building a cell therapy portfolio, only to ultimately walk away, is explored. Pfizer wins the bid for Metsera, Amgen offers Repatha at a discounted rate, and Roche acquires Akero for $3.5 billion. Biospace also honors 40 under 40 winners making an impact in the industry.Peter Marks, former director of the FDA's Center for Biologics Evaluation and Research, has taken on a new role as Senior Vice President for molecule discovery and the head of infectious diseases at Eli Lilly. Marks' controversial exit from the FDA led to his hiring by Lilly, following in the footsteps of another former FDA official, Rachael Anatol. Marks confirmed his new role to Stat News and began his first day at Lilly Research Laboratories on Monday.Support the show

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world. Former NIAID director Jeanne Marrazzo was fired after filing a whistleblower report, alleging retaliation. The FDA's new cell and gene therapy guidances have been well-received for streamlining therapies. In other news, CMS has finalized stronger protections for orphan drugs, and Amgen's Repatha has shown positive results in preventing heart disease. Lotte Biologics is highlighted as a multinational CDMO partner, and layoffs at CSL Vifor and Takeda are noted. Trump has delayed pharma tariffs, Pfizer's drug pricing deal with Trump raises questions, and GSK CEO Emma Walmsley's departure is discussed. Thank you for listening to the latest updates in the Pharma and Biotech industry. Stay tuned for more essential news in our next episode.Support the show

In this special sponsored episode from Takeda, Angelina Collins, a Nurse Practitioner at a large tertiary inflammatory bowel disease (IBD) center in California, shares insights from her nearly two-decade journey in IBD care. She explores the challenges of diagnosing Crohn's disease and ulcerative colitis, from varied symptom presentation to limitations in early recognition. Emphasizing the potential consequences of delayed diagnosis—including disease progression and increased risk of complications—Angelina advocates for early identification of red flags and a multidisciplinary team approach to treatment and care. She highlights the critical role of advanced practice providers and the importance of expanding IBD knowledge across health care teams. Listeners will come away with insights on how to recognize red flags, apply best practices for timely referrals, and leverage collaborative care models in IBD management. READ THE ARTICLE → https://kevinmd.com/takeda Are you a health care clinician looking to increase your IBD knowledge? Visit IBDIQ.com, part of The IBD Project, to continue to evolve your IBD knowledge for yourself and your patients. Developed by Takeda in collaboration with IBD specialists and created for health care providers, IBDIQ is an on-demand educational platform, available at no cost, that offers timely, relevant information tailored to today's IBD care landscape: https://www.ibdiq.com/ Please note, no continuing medical education credits are offered through IBDIQ. VISIT SPONSOR → https://www.ibdiq.com/ SUBSCRIBE TO THE PODCAST → https://www.kevinmd.com/podcast

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.

What if process intensification could transform your bioprocessing economics without the complexity most engineers fear? Getting 3x productivity gains and 30-150% titer increases once seemed reserved for Big Pharma's endless R&D budgets, but a strategic approach to technology selection is making these results achievable for companies of any size.In this episode, David Brühlmann speaks with Andreas Castan, a bioprocess veteran with over 25 years of industry experience who provides leadership and support to Cytiva's bioprocess business. Andreas brings deep expertise from directing upstream development at Swedish Orphan Biovitrum and extensive work in expression systems, process development, scale-up, and cGMP manufacturing across multiple therapeutic modalities.Why tune in? Here's your process engineer's roadmap:Process Intensification Economics Decoded: Andreas reveals the cost-benefit reality behind continuous vs fed-batch manufacturing, including real process economic modeling data showing why the differences aren't as dramatic as you'd expect and what factors actually drive your business case.Low-Hanging Fruit That Delivers: Skip the overhyped AI solutions. Andreas shares the strategic fundamentals that work: high-producing cell line development, N-1 perfusion for rapid productivity gains, and smart bioreactor turndown strategies that eliminate process steps without adding complexity.Decision Framework for Technology Selection: Learn when continuous processing makes economic sense (and when it doesn't), how media costs impact your COGS analysis, and why understanding your bottlenecks, not following industry trends, should drive your intensification strategy.Industry Insider Strategies: Get the inside track on what AstraZeneca, Sanofi, Merck, Lonza, and Takeda are actually implementing, plus Andreas's perspective on why human expertise and mechanistic insights still outweigh AI in real-world process decisions.Ready to make smarter technology investments and achieve measurable productivity gains? This isn't theory. It's a practical guide to process intensification economics that you can apply whether you're preparing for Phase I or scaling for commercial manufacturing.Connect with Andreas Castan:LinkedIn: www.linkedin.com/in/andreas-castan-91570b1Cytiva landing page: Process intensificationOnline tool: Process intensifierNext step:Book a 20-minute call to help you get started on any questions you may have about bioprocessing analytics: https://bruehlmann-consulting.com/call

温かさと厳しさを併せ持つ武田鉄矢が毎週テーマに添ってさまざまな語りを展開。どんな話題でも美味しくさばいて見せマス！さらに、Podcastでは配信されていない2006年以降の音源をお楽しみいただけるサービスが「QloveR」にて展開中！毎週月曜日に1週間分ずつアーカイブ音源が更新され、掲載されている音源は何度でも聴き放題です！ぜひご登録の上お楽しみください。登録はこちら→https://qlover.jp/takeda [毎週月曜更新]See omnystudio.com/listener for privacy information.