British teenager Shauna Davison received an experimental transplant in 2012 in the hope of prolonging her life. Her mother tells her she was told in advance about two patients who had survived such a surgery – but not for others who had died. BBC Deborah Cohen asks if Shauna, who died in two weeks, has been the victim of the urge to develop stem cell technology?
Shaun Davison was born with a lung, with a cleft on the palate and a big heart defect. But although she spent her life in and out of the hospital, she was a happy child. "Her illness never knocked her off, and she always had a smile on her face," says Shannon's mother, Karen Davison. "Everyone was so nice to her, they were looking beyond her problems."
When he was 12 weeks old, doctors found tracheal or tracheal problems. It was very narrow, and when she got hurt she could not breathe. She received 48 hours to live.
A surgeon from Leeds came to the rescue. David Krabe warned that he might fail, but he managed to restore Shaun's trachea from her ribs. Shona had to stay in the hospital for six months and have ring-shaped stents placed in her trachea to keep her open.
Mr Crabbe really cared, says Karen Davison. "The hospital was exceptional.
Over the years, Shauna's stents needed expansion until it grew bigger. She had tracheostomy – a hole in the front of her neck – to help her breathe.
"There were times when we did not think it would succeed, because it continues to collapse," says Karen Davis.
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At Middlesbrough, she learned how to change Shaun's tracheostomy tube, use a ventilator, physiotherapy to help clear her breathing path, suck the airways, make CPR, and give her IV antibiotics. "I did everything for her," she says. "Shuna has done amazing. But she knew nothing else.
A fan of the Middlesbrough football club, Shauna liked to wear a football set. She went to a general school with the support of a carer where she could mix with other children. "She was a child but loved by everyone," her mother said. "She illuminated the day at all."
The Shuna had a lot of operations, but she's always gone. Sometimes she has not been approaching a hospital for centuries, says Karen. However, the time came when David Kraby told her that his shun healing technique would no longer be enough. Her breathing paths were too small and had to look for other possibilities. "Mr. Crabbe showed me pictures of a normal breathing path and her breathing paths, and it was small," said Karen Davison.
Shauna began walking at Great Ormond Street Hospital (GOSH) in London for testing and changing his stent. In 2011, doctors told her that the airways would not last long.
At 15, Shauna suffered a breathing arrest – a serious incident she could not breathe – and his family was reported as an innovative operation by Professor Martin Elliot, surgeon cardiothorac and former medical director of Great Ormond Street Hospital. 19659004] "They said there were studies of tracheal transplants and there were two other cases in which this was done, but they could not discuss it with me because of patient confidentiality," said Karen Davison. One of them is a 10-year-old boy, she adds.
"That would be the only chance he would have."
Shaun's transplantation was not conventional.
She would get a donor tube, but it would have been filled with her own stem cells, which would do just like hers. There would be no need for drugs to stop her body from rejecting it. She was at the forefront of the new stem cell technology – and is still very experimental.
Doctors can use experimental treatments if someone is terminally ill and there is no alternative treatment. It is called "compassionate use". Karen says she was told that Shauna would not need a tracheostomy or a fan, and she would have a normal life. But she is also told about the risks, she adds – Shona can reject the transplant, and the presence of general anesthetic is never safe.
Previously, Martin Elliott worked closely with internationally-known Martin Burchell, a professor of ENT at UCL, for implanting a donor trachea with a stem cell donor into another child. They will work together again in the case of Shaun.
Shown was treated at Great Ormond Street during a BBC documentary about the hospital in 2012. She was appreciated by various specialists and asked her what her hopes for the future are. Shauna told Dr. Ronald Wallace that she wanted to be able to swim. The decision for the operation was not easy. Martin Wallis said that was not a situation where he had nothing to lose.
"They have a lot to lose, and that will lead to a difficult decision," he said. "She has a reasonable quality of life, has a good friend, obviously has a sense of humor and enjoys – it makes it harder."
"I wanted her to do it while it was better than to wait until it felt bad and it could not happen," says Karen Davis.
But since this was an experimental procedure, her medical team discussed it with the ethics committee of Great Ormond Street Hospital.
"I do not think she will die if we do the procedure, we try to do the procedure so it does not do it, or at least extend her life and quality of life for as long as possible." Surgeon Martin Eliot , she tells the committee in front of the camera. "They could not give me time when she would die, but they said she would die eventually. Because her airways will just give up. So there was such a procedure that they said they were ready to do, "says Karen Davison." Like any other parent, if you thought this would help your child live, I agreed. "
So in February 2012, Shauna was given a transplant of a donor trachea recently populated with its own stem cells
Originally everything looked good. "She was wonderful in the first few days," she remembers her mother. "I could not believe how well she had recovered after her."
Two weeks after her surgery, Shown was moved from Big Ormond Street to an ambulance at Leeds Hospital. But during the transfer, Shuna began to cough a lot and needed suction to clear her throat.
"We thought this was odd, but I thought it could be due to the journey," says Karen Davis. "I just thought," A few more weeks and we'll go home. "But the next morning, Shuna turned to worse, remembering Shauna saying," Help me, help me. "" It was the worst day in my life because I could not helped. "
Shuna's new trachea collapsed." They said she had struggled so much to breathe, her heart had given up. Karen Davis says.
"She was a wonderful child, I miss so much."
When the first transplant was done in 2008 with donated cane, covered with the patient's own stem cells, she made global headlines. It is believed that stripping the donor cells from the surface of the trachea and placing it in the patient's own stem cells creates a new organ that would be like the patient's own tissue. Anti-repellent drugs would not be needed for the "tissue engineering" trachea.
The surgery was performed by Italian surgeon Paolo Machiari, with the help of Martin Birch, then a surgeon at Bristol University. The recipient is 30-year-old Claudia Castillo, who has tuberculosis in a part of the trachea that leads to her lungs – bronchus
Her case is recorded in The Lancet. Five months after her surgery she was reported to be in good health.
Martin Birchall, who helped prepare the donor trachea, said at the time that "it would be a huge step in surgery." Now surgeons can begin to see and understand the potential of adult stem cells and tissue engineering to radically improve his ability to treat patients with serious illnesses. "
Many of the world's consensus was" a cornerstone of medicine, "" good news, "and" an exemplary example of international co-operation. " revolutionary, which is highly innovative … opening the door to new and exciting technologies using stem cell marriage and artificial skeletons that could lead to this completely new field of regenerative medicine, "recalls Professor John Rasko, president of the International Society for Cellular Therapist
He had the Nobel Prize for it, he said.
In fact, soon the university distributing the Nobel Prize for Medicine, the prestigious Carollo Institute of Strolling, offered Macchiarini the post. Birchall, in turn, moved to University College London (UCL), where Macchiarini is also an honorary professor.
Claudia Castillo's operation serves as a template and others have similar procedures soon. In 2010 Professor Birchall said at the conference "We Made Another Five Adults."
Besides Shauna, UK tissue-engineered patients include 19-year-old Keziah Shorten and 10-year-old Ciaran Finn-Lynch. Shauna's surgeon, Martin Elliott, heads the transplant team that carries out the operation of Ciaran, with the help of Macchiarini and Birchall. Like Claudia Castillo, his procedure was published in a medical journal and she received global titles. Martin Birchol told reporters: "He has a healthy body made from his own stem cells and somehow is like a miracle."
be asked about trachea covered with stem cells.
This meant for McKiaryini that his meteoric rise was reflected by the rapid fall of grace. He had gone from using donated trachea to plastic, which was also covered with stem cells. The results are catastrophic – his patients have died.
Makariari was investigated several times by Karolinska before he was fired. The allegations against him were initially rejected, but since then the institute has found him guilty of scientific misconduct, and many of his scientific papers have been withdrawn. In December last year, the Swedish Prosecutor's Office resumed the investigation into criminal negligence against him.
Bo Rissberg, a professor of surgery at the University of Goetheberg and a former chair of the Swedish Ethics Council, said the events were the biggest research scandal that Sweden has experienced today.
a carpet, "he said. Machirini's failure to perform pre-clinical tests on animals using plastic trachea is "the worst crime you can do," he added. argues that it is "impossible from a theoretical point of view" to establish a new blood supply to the tissue engineering trachea, whether it is plastic or donated.
In 2015, he wrote to UCL that he was questioning the idea of "tracheal" regeneration, calling him "the biggest lie in medical history." At that time, Machirani left UCL
In his subsequent unpublished report on Delear's claims, seen by the BBC, UCL questioned the assumption that stem cells "played a therapeutic role" in Ciaran's operation.
But, he said, there was no "deliberate deception" or "intent to deceive" the part of Martin Berhol. Due to the "lack of intention to mislead", the university recommends education and training and not other formal procedures. Meanwhile, the university has been preparing to conduct clinical studies of trachea and larynx, regenerated from stem cells called Inspire and RegenVox respectively. Martin Burchell was the principal investigator with the responsibility to lead the trials. He and his team will bring millions of pounds to fund research at the university.
It's not the only time UCL made a report on regenerative medicine at the university. In 2017, it published the conclusions of a special study, created after Macchiarini's revelations. He did not blame Martin Burchell and clear the way for future clinical trials.
It was said that Shaun's family was grateful for the opportunity her daughter had received and had no dislike for the trachea team at the GOSH.
UCL told the BBC that this was "reported to the investigators by Shauna Davison care physicians."
But Shaun's mother, Karen Davis, says no one involved in the investigation has ever asked about her views.
The more I looked at Shaun Davison's story, the more I discovered that Karen Davison did not know.
The two patients Karen and Shauna heard were the ten-year-old boy, Kiir Finn-Lynch and Claudia Castillo, both alive.
But they were not told that Claudia Castillo's transplantation had collapsed a little over three weeks after she received it, and they needed stents to open it. Karen and Shauna have not heard of most of the other cases that Martin Birhal has spoken in 2010.
One of these operations was Kent, teenage Kesia Shorten, who was about two years earlier to have received tissue engineering a donor trachea from Macchiarini in Florence after having been diagnosed with a rare form of cancer.
But about a year after surgery, her transplant failed. Martin Birchol told a Swedish documentary in 2016 that her trachea was broken. When she was subsequently operated at University College London Hospital, she replaced her with plastic. She died a month before Shaun's operation
According to John Rasko, "there is a strong obligation to give full and frank information about all available information." The exclusion and exclusion of bad cases is something that is unacceptable. 19659004] A spokesman for GOSH said: "As a patient, the condition of Kesia and her graft are very different from Shauna, so it is not clinically relevant to discuss her case."
The hospital added that the other patients were not being discussed "because the team did not know about other important cases from abroad at that time."
There was something Karen and Shona did not know, and they heard about Kianar Finn-Lynch. But there were key differences between Shaun's operation and his
Kiran had received a stent – but Shona did not do it. "According to the UCL's 2017 Investigation Report, Martin Elliott said he wanted to use a stent knife but was advised not to do it
Ciaran also received a fresh donor trachea, the shouna was not fresh, it was frozen, and then broke This is a treatment that was not used before – after the trachea was thawed, the donor cells were removed using a special vacuum technique, except for the members of Shauna's medical team
Trish Murray, Professor of Stem Cell Biology and Regenerative Medicine at Liverpool University, has a number of criticisms. "The reality is that if you do not have a stent, the trachea will collapse, this is the unanimous experience of all patients who have had a tracheal transplant," she says. "So, although it is well known that stents cause trouble if you do not have a stent, the trachea will crash and the patient will suffocate. "Another problem was the frozen trachea, and the team had the effect of freezing the trachea, as the trachea could be pre-stored and thawed as needed. But Trish Murray is also critical of this decision. "
" The Kia Trachea and was not frozen in advance until Shuna was frozen, and we in the reports know that the group itself has posted that it will weaken the trachea … and this will make it more likely to crumble once it has been implanted,
However, UCL is questioning the feasibility of these studies, he told the BBC that they did not refer to the technique used for Shaun
Trish Murray says other alarming studies should ring . Тя посочва едно непубликувано изследване, което разглежда вакуумната техника, което показва, че едно прасе, което е получило трансплантация, умира спонтанно, а друго – „респираторен компромис“ и е трябвало да бъде свалено. Изследването е спряно на хуманни причини.
"Ние знаем от информация, която е получена от заявленията за свобода на информацията, че екипът в UCL са опитали техниката на две прасета и двете прасета са умрели доста бързо. за зайците и 100% смъртност при зайците, казва тя. Би Би Си попита UCL и Great Ormond Street дали изследванията с животни са били извършени преди или след операцията на Shauna, но не са получили отговор на този въпрос.
И като белгийския преподавател по УНГ Пиер Делеър, Триш Мъри задава въпроса за ролята на стволовите клетки. "Всъщност няма доказателства, че някоя от тези клетки о елява, всъщност доста доказателства, че те не оцеляват, – казва тя.
Но как лекарите и учените участват в грижата за тежко болни пациенти, които могат да използват тези трахеи, когато има малко доказателства, че те работят? Обикновено изследователите трябва да проверят иновациите си в лабораторията и след това върху животните в предклиничните изследвания. Едва тогава – с официално одобрение от комисията по етика за научните изследвания и регулаторите – се премества в хората.
Мартин Бърчъл обаче пише в "Ланцет", че "състрадателните проучвания", процедурата за използване на нови лечения при много болни пациенти, са "мощни начини за информиране за строго планирани официални изпитания" и "ускоряване на тестването на нови терапии"
"Включените хирурзи са използвали тази очевидна вратичка на милосърдното използване, за да експериментират с пациенти и след това са използвали данните, които са получили, за да отидат при регулаторните органи, за да получат разрешение за изпитанията," Триш Мъри
Джон Раско се съгласява с Триш Мъри, че системата не трябва да работи така.
"Упражняването на възможността за състрадателна употреба носи със себе си голяма отговорност. Не бива да се използва като начин, по който лекарите могат да летят под радара на правилно предприетата регламентирана медицинска практика, ”казва той.
И Грейт Ормънд Стрийт също се съгласява. "Ние не виждаме състрадателната употреба като начин за изследване на нови лечения", каза говорител.
Но трансплантацията на Shauna, както и тези на други пациенти, бяха използвани за получаване на финансиране и одобрение за клинични изпитвания, к кто и за писане в медицински списания и заявление до Европейската агенция по лекарствата.
Би Би Си установи, че най-малко седем от тези документи и публикации представят по някакъв начин погрешното лечение на Шауна или смъртта.
Например в една молба за 2016 г. до Европейската агенция по лекарствата Мартин Бирхал е цитиран като начална операция на Шауна. е била успешна, но тя е претърпяла "фатално сърдечно-съдово събитие шест седмици след операцията" – докато всъщност тя е починала след две седмици, тъй като трахеята й се е сринала. и финансирани от публични органи, е направена промяна в процедурата. След като научил какво се е случило с Shauna, екипът щеше да се увери, че пациентите в процеса са имали стент.
И дори тогава одобрените информационни листове за пациента, придружаващи едно от изпитанията, съдържаха погрешна информация за Shauna и наистина за Claudia Castillo. Само те и Сиран Фин-Линч бяха включени в информационния лист – въпреки че екипът знаеше най-малко 10 случая в световен мащаб.
Още през 2014 г. Мартин Елиът каза на конференция, че 10 пациента са получили трахеята с тъканни инжекции, всички
Миналата година клиничните изпитания бяха преустановени.
Голяма част от това, което Би Би Си разкри за случилото се с Shauna, не фигурира в специалния доклад за проучване на UCL.
Леонид Шнайдер е молекулярно-клетъчен биолог. журналист, който от 2016 г. покрива регенеративната медицина. Той бе призован да даде показания в разследването на UCL и е проклет в оценката на доклада си.
"Защо майката на Шауна не разполага с пълната информация? И чиято идея не беше да й дам стент? той пита.
"И накрая, как биха могли изследователите на UCL да препоръчат клиничните изпитвания на донорската трахея да се възобновят, след като професор Delaere и аз им казахме колко хора са умрели от него?"
UCL казва, че клиничната помощ е „извън обхвата на проучването“.
Той добавя: "Всяко изследване, проведено в UCL се изисква да отговаря на най-високите правни, етични и регулаторни стандарти, и ние няма да се поколебаем да предприемем не бходимите действия, ако и когато това не успее."
След получаване Етични съвети, казах на Карън какво е разбрал Би Би Си за трансплантации с тъканно инженерство.
Тя е разстроена. Тя каза, че това може да е променило решението й за разрешаване на операцията на Шауна.
"Надявам се, че никой друг не трябва да мине през това, което съм преживял, наистина го правя. Те трябва да бъдат спрени. It's such a shock. Хората ме питат:" Как е умряла Шона? " И винаги казвам, инфаркт. Никога не съм обвинявал тези хирурзи за смъртта й. Те имат много за какво да отговарят. "
ГОШ каза:" Преди операцията на Шауна беше извършен цялостен преглед на всички релевантни публикувани научни и медицински доказателства. "
Те също така казаха:" Съжаляваме, че лечението не е работило за Шауна и семейството смятат, че не са получили цялата необходима информация. Свързваме се със семейството на Шауна, за да им предложим да се срещнем с тях, за да говорим през всичките им притеснения. "
" Всичко това им е отнело през цялото това време, но бихте си помислили, че биха ми се обадили и ми казали нещо ", казва Карен Дейвисън. "Знам, че не бих я имал завинаги, но поне може би съм я имал малко по-дълго."
Снимки на Шауна Дейвисън с любезното съдействие на Карън Дейвисън