Trachea surgeon Macchiarini acted “without due care,” but is not guilty of misconduct: Karolinska

Paolo Macchiarini
Paolo Macchiarini

Following an investigation, Karolinska Institutet has found that surgeon and visiting professor Paolo Macchiarini acted in some cases “without due care,” but that his behavior “does not qualify as scientific misconduct.”

Karolinska’s Vice Chancellor has also recommended that Macchiarini submit an unspecified number of corrections “to clarify and rectify the failings that the inquiry has brought to light.”

Macchiarini is most well-known for pioneering the creation of tracheas from cadavers and patients’ own stem cells. However, the glow of his success was diminished somewhat after four Karolinska surgeons filed a complaint, alleging Macchiarini had downplayed the risks of the procedure and not obtained proper consent, among other accusations.

An external review by Bengt Gerdin of Uppsala University concluded in May that Macchiarini had committed misconduct in seven papers. All co-authors on the papers had two weeks to respond, after which the vice-chancellor would reach an official decision.

That decision, announced today during a press conference (and summarized in a press release from Karolinska), was that

…while on some points Visiting Professor Paolo Macchiarini did act without due care, it does not qualify as scientific misconduct.

Vice chancellor Anders Hamsten said in a statement:

Now that we have examined the allegations of scientific misconduct in all seven indicted articles, we have found that they contain certain flaws but nothing that can be considered scientific misconduct.

Hamsten said Gerdin’s

…examination was extremely valuable for the inquiry, but the documents to which he had access lacked significant data on the pre- and postoperative status of two of the patients. The comments sent in by Professor Macchiarini and his co-authors have had a significant influence on how the case has been assessed. Now that we have all the relevant material on hand, we have a much clearer picture of what happened.

We’ve obtained and made available that response by Macchiarini, as well as the rebuttals from four of his accusers.

As the Karolinska statement notes, Macchiarini’s accusers

pointed out that the results concerning the patients’ clinical progress as expressed in the papers did not match the patients’ medical records as kept at Karolinska University Hospital, and that there was no evidence that a synthetic tracheal transplant can develop into a functional airway. They also questioned the claim that the first patient had suffered a relapse of his tracheal cancer and that surgery was therefore necessary.

The four doctors also

criticised Professor Macchiarini for not having obtained a permit from the regional Ethical Review Board and the Swedish Medical Products Agency before the operation. However, Karolinska Institutet did not examine this issue in its inquiry since the Swedish Research Council’s definition of scientific misconduct does not cover breaches of the Ethical Review Act and the Medicinal Products Act.

At the same time, Karolinska Institutet concluded that a decision to perform the three operations was taken by the hospital.

“Karolinska University Hospital made the decision to operate following a transparent process and in what it saw as the absence of alternative therapeutic solutions,” says Professor Hamsten. “These decisions did not address research aspects.”

Karolinska did identify some issues:

The inquiry shows that the interaction between Karolinska Institutet and Karolinska University Hospital has not functioned satisfactorily, and the Vice-Chancellor’s decision promises improvements to procedures, regulations and support structures for clinical trials and clinical therapy research. The line between clinical application and research when it comes to experimental therapy will need to be better defined, and clearer guidelines for academic research and academic healthcare will be drafted.

Professor Macchiarini has also been instructed to submit errata to the journals that published some of the scientific papers to clarify and rectify the failings that the inquiry has brought to light.

“Some aspects of Paolo Macchiarini’s research do not meet our high quality standards,” says Professor Hamsten. “We will now be remedying the deficiencies our inquiry uncovered with him, the heads of his department and representatives from Karolinska University Hospital.”

This is one of two reviews commissioned by the Karolinska. The other cleared him of different allegations brought by Delaere. An investigation in Italy has also found him not guilty of most charges.

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3 thoughts on “Trachea surgeon Macchiarini acted “without due care,” but is not guilty of misconduct: Karolinska”

  1. Whatever the fine detail of the investigations into Macchiarini’s work on vascularized tracheal allotransplants modified by stem cells, the hope that this was Nobel-prize winning research has evaporated. As Delaere has pointed out elsewhere in Retraction Watch, the prior probability that Macchiarini’s technique would be successful is so low that other explanations must be more likely.

  2. Claudia Castillo, who received the first artificial trachea in June 2008, is still alive and in good condition. And Ciaran Finn-Lynch, the second transplanted patient, is alive and in very good condition, five years after surgery

    When I affimed this elsewhere in Retraction Watch, Delaere replied: “The reason why these 2 patients are still in ‘good condition,’ I believe, is because of a stent, a synthetic tube that keeps the airway open. The stent was in place from the very beginning. Until now, devoted doctors have succeeded in treating the complications, which are typically linked with an airway stent. This has nothing to do with tissue engineering or regeneration.”, but this statement is wrong, since Ciaran Fynn-Lynch got a transplanted trachea after failure and complications of the stents he had received previously.

    An Claudia Castillo required a stent at the anastomosi level only (“The graft behaved as expected until 6 months after surgery. Thereafter, the proximal (native to tissue-engineered trachea) anastomosis began to show a progressive cicatricial diaphragm-shaped scar. The remaining tissue-engineered trachea and distal anastomosis were patent…. By contrast, no stenotic formations developed at the distal bronchial anastomosis and the rest of the graft remained patent during the 5 years of follow-up” Gonfiotti A, et al. The first tissue-engineered airway transplantation: 5-year follow-up results. Lancet. 2014 Jan

    Mr Beyene had a tracheal cancer, and had a good life for more than 1 year after transplantation.

    Moreover, Delaere affirmed that “The sad truth for the synthetic trachea is that implantation inside the airway will always lead to the death of the patient in the short or mid-term. Patients die due to anastomotic breakdown, which becomes visible within a couple of months after surgery. Moreover, although most people are willing to believe anything as soon they hear the term ‘stem cells’, transformation of a synthetic or de-cellularized trachea into a vital structure that is built up by living cells is theoretically impossible. Indeed, no experimental evidence for such a miraculous transformation is available.”

    In the case of Claudia Castillo “1 year after transplantation, biopsy samples showed complete re-cellularisation of the bioengineered airway, with the presence of seromucus glands… At 2 years, haematoxylin and eosin staining showed simple ciliated columnar epithelium with a basement membrane (figure 3E, F). The last biopsy sample (taken December 2012) showed a pseudostratified, ciliated, columnar-type epithelium with areas of immature metaplastic squamous epithelium (figure 3G, H). Laminin immunostaining confirmed the presence of a continuous layer of basal membrane and small blood vessels (figure 4)…. In June 2012, we detected a completely re-cellularised airway (figure 6G, H), with a morphology very similar to the native airway ” (Ibid.)

    Also in the case of Ciaran Finn-Lynch “Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity.” (Hamilton NJ, et al. Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study. Am J Transplant. 2015 Jun 2. )

    So, is it IMPOSSIBLE or just hard to perform tracheal transplants with bioengeeniring?

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