Macchiarini investigations outcome: Karolinska University Hospital

Investigations into lethal patient abuse by the thorax surgeon and regenerative medicine “pioneer” Paolo Macchiarini are now concluded in Stockholm. The Karolinska University Hospital (Karolinska Universitetssjukhuset, KS) published their investigative report on August 31st, the Karolinska Insitutet (KI) will follow with theirs on September 5^th.

The KS investigation was chaired by Kjell Asplund, emeritus professor in medicine at Umeå University, who is also chairman of the Swedish Council on Medical Ethics (Smer) and former director-general of the National Board of Health and Welfare (Socialstyrelsen). The Asplund report found gross violations of medical ethics, patient right, even recruitment processes when analysing the history of the scandal around the Italian surgeon. Unlike repeatedly declared by both KI and KS, Macchiarini’s trachea transplants were not medical emergencies and not compassionate care cases:

“There was no immediate threat to the life of any of the three transplant patients before the operations”.

Unethical research, not humanitarian care

These interventions were now determined as clinical research and as such were supposed to be subject to ethics vote and medicinal product approval.  This in stark contrast to previous declarations by KI and KS leadership, namely that Macchiarini’s trachea transplants were merely humanitarian care and medical emergencies. Now the Asplund workgroup rebukes in their Swedish-language report:

“We question the hospital’s stubborn position in defence of transplants’ clean health care initiatives”.

No such ethics or medicinal product permits were obtained or even applied for, in fact the investigative committee made clear that in view of all scientific and clinical evidence “it is unlikely that the project would have been approved”. The patients and their families were coerced into signing their consent, despite that

“the written information contained texts that neither made it possible for the patient to understand the content or refrain from the procedure. If the information had been presented to an ethical review board, it would not have been approved. The patients were not given any possibilities to discuss the operation decisions with an independent expert”

The leaders of the hospital departments involved were assigned their share of responsibility for this patient abuse. In fact, KS director Melvin Samsom announced at a press conference that the heads of the ENT clinic and of the Theme Center for Cardiovascular Diseases are suspended “until further notice”.

Correction 2.9.2016: Since Samsom did not name anyone directly, using Karolinska website I originally fingered Jesper Haeggström and Lars-Oliver Cardell. This an error of mine, as a reader corrected me. These two heads were not suspended, but the two lower-rank faculty members instead:  Ulf Lockowandt and Bo Tideholm, as mentioned in Dagens Nyheter).

The Asplund investigative report dismisses the trachea transplant experiments not only in the clinical aspect, but also scientifically:

“Our collective assessment is that there was not an adequate scientific foundation for a human transplant of a synthetic trachea seeded with bone marrow cells, combined with the application of growth-stimulating drugs”.

The latter intervention, this excessive application of growth factors like erythropoietin and G-CSF outside of any scientifically established rationale, may have likely contributed to patients’ demise:

“There was no permit from the Swedish Medical Products Agency to use the growth stimulants for this purpose and in the doses provided. All three patients were struck by large clot formations and it cannot be ruled out that the drugs may have contributed to this”.

Putting genie back into the bottle

In this regard, the lack of supervision Macchiarini enjoyed at KS proved fatal. The investigators write in their English-language summary:

“Macchiarini is a thoracic surgeon, but it was decided that he would have his academic and clinical activities placed with the ear-nose-throat division (ENT unit) at KI and the ENT clinic in Huddinge (the thoracic clinic is in Solna [which is around 25km away, -LS]). It is our impression that the KI management was the driver of this decision. The fact that Macchiarini was employed at the ENT clinic in Huddinge, but came to locate most of his surgical activities at the thoracic clinic in Solna contributed to unclear responsibility circumstances, which gave an independent person like Macchiarini an opportunity to move between the two clinics too freely”.

We now also learn that Macchiarini was installed at Karolinska Hospital by the pressure from the KI despite many warnings against his character. He was described by all references from Florence, Hannover and Barcelona as “a technically dazzling surgeon”. But Karolinska was also repeatedly warned about Macchiarini:

“From Italian side [according to report, Dean of the Medical Faculty in Florence and two other colleagues, who also voiced suspicions of misconduct in research and suspicion of financial irregularities, -LS] it was stressed that he did not care about the ethics aspect. In Italy, his CV was challenged by a review committee of the University of Florence in connection with application for professorship (for which he was not deemed to be qualified). His employment in Italy and Spain had been concluded on the employers’ initiative.  Negative signals also came from Hannover [Medical University Hannover, -LS], where he was not a university employee but operated private patients. There, cooperation with Macchiarini was concluded because of his inability to accept common decisions”.

For details of Macchiarini’s bullying and his near-lethal patient intervention in Hannover, see my report here. A clinical colleague from Barcelona informed Karolinska of Macchiarini’s “difficult personality and cooperation difficulties” as well as his monetary greed. The Italian surgeon used to take on Spanish patients which his colleagues deemed inoperable, most of whom then died. He took them on privately, meaning their desperate families had to pay huge sums of money directly to him. However, KI was set on recruiting this star scientist surgeon nevertheless.

One reason was ACTREM, the Advanced Center for Translational Regenerative Medicine, which Macchiarini planned to establish at Karolinska with huge public funding.  Using cadaver and plastic scaffolds, multiple organs and chest tissues were to be grown and transplanted into his patients: trachea, lungs, heart, chest wall, diaphragm and oesophagus (see paper Sjöqvist et al; Nature Comm, 2014). KI has by now dissolved the ACTREM Group.

There were even bigger plans, which might explain why so many senior scientists and clinicians at Karolinska switched off their brains and chose to look away, dreaming of international fame and obscene money. Macchiarini also had a vision of a “European Centre for Advanced Regenerative Airway Surgery”, to be located in Stockholm, London and Florence. The Asplund team interviewed in this regard Macchiarini’s partner, the UCL throat surgeon Martin Birchall. Togetehr, the two pioneered both the cadaveric and plastic trachea transplants, with disastrous outcomes. Apparently, Birchall feels his great vision has been stolen from him, since he indicated that “the initiative came from him but that Macchiarini on its own accord took over the control from Stockholm”.

Probably because of this, the reports note that the duo is “no longer on good terms with each other”. Birchall was however compensated by the EU, which gave him €7Mio for his own Europe-wide trachea replacement programme, see my report here. Back in 2010 though, the British laryngologist did his best to help his partner get the job at Karolinska, as the Asplund team wrote:

“E-mail correspondence shows that KI sought advice how to balance the negative image which Macchiarini received from Italy, Spain and Germany. It leaned heavily against the relatively favourable picture received from London, primarily from Martin Birchall, and they were afraid that the good cooperation with University College of London and Great Ormand Street Hospital would be jeopardized if KI rejected Macchiarini. There was a notion that Macchiarini’s personal shortcomings still could be handled – that it ‘may be possible to keep this man under control, as they apparently did in London’ “.

Swedish Experimenten: two dead, one barely survives

The Asplund workgroup analysed medical files of three patients who received plastic trachea transplants from Macchiarini at KS (see summary below). Two of this patients died, the third one is in a very bad medical state. For the first two operations, Macchiarini organised a multidisciplinary conference to debate the transplant decision. For the third patient, he decided singlehandedly. The medical abuse will now be reported to Swedish authorities under the provision of the Swedish regulations of Lex Maria (according to the Asplund report, there already was an earlier Lex Maria incident of a different airway surgery by Macchiarini, in 2011).

It also turned out that the star scientist Macchiarini was not really taking the clinician’s side of the transplants seriously. He delegated most of the patient-directed work to his German acolyte Philip Jungebluth, who according to the report “had no permit to work as a doctor in Sweden” (Jungebluth currently is acquiring his qualifications as thorax surgeon at the prestigious university of Heidelberg, see my report here). The Italian star surgeon invited staff from the plastic-trachea manufacturer Harvard Apparatus (now renamed BioStage) to his trachea transplant operations and even allowed them to film them, all without informing the patients. The Asplund report mentions that:

“Macchiarini was only present during certain key moments of the first transplant and, according to oral information we received, it happened that during that day he appeared in “plainclothes” in the operating room”.

These are the three trachea transplant patients whose medical records the Asplund committee scrutinised in detail (please also refer to my earlier article for background):

• Patient 1, Andemariam Teklesenbet Beyene, 36 years old, operated in June 2011, died in January 2013. The intervention was justified by Macchiarini by the alleged throat cancer recurrence, which was however never proven by biopsies. After the patient’s death, the autopsy found chronic chest infection, blood clot in the lung artery and that the plastic trachea came near completely loose. But no remaining cancer.
• Patient 2, Chris Lyles, 30 years old, previously treated for non-metastatic trachea cancer by chemo- and radiation therapy. He received a plastic trachea transplant in November 2011, and died suddenly in March 2012. Strangely: “no autopsy appears to have been performed”.
• Patient 3, Yeşim Çetir, 22 years old, operated in July 2012. She was a victim of a botched nerve surgery in Turkey to cure her sweating hands, which left her with a severe trachea injury and a non-functional right lung. Machiarini removed it and then installed a plastic trachea, which soon proved leaky and started to collapse. So Macchiarini installed a new plastic windpipe, while the patient experienced blood clotting and kidney failure. Her oesophagus had to be removed du to fistula formation; her airways had to be constantly cleaned out. The plastic trachea was removed as well, to save the patient’s life. All this was none of Macchiarini’s concern though: he was not interested in his patient anymore. In May 2016, Yeşim received a multiple organ transplant in the US. These transplants were “normal”, living human donor organs, not miraculously regenerated dead tissues or plastic Macchiarini has been peddling. Of all the patients Macchiarini transplanted with plastic trachea, Yeşim is apparently the only one who so far survived the intervention, no thanks to him though.

If no one minds, why not trying?

Thanks to Asplund-led investigation, we now know why Macchiarini decided to use plastic for his trachea transplants in the first palce, despite the fact that these were too rigid, could hardly be sutured in, collapsed quickly or simply came loose, suffocating the patient and releasing into the patients’ chests a toxic flow of bacteria and fungi which grew inside them. Macchiarini problem was time: the decellurisation process for cadaveric tracheas took too long a time for this impatient adventurer. When Macchiarini was first tested his plastic tracheas on rats, all of them died: half of them within two days. Like with his deceased human plastic trachea recipients, these results were not published. Instead Macchiarini simply repeated the animal experiment, which suddenly proved a 100% success: all eight rats were doing great. At least this is what his three papers claim (Jungebluth et al,  Biomaterials, 2013; Ajalloueian et al, Biomaterials, 2014; Jungebluth et al, Nature Protocols, 2014).

Aside of the three patients in Stockholm, Macchiarini transplanted five more with plastic tracheas outside of Sweden, primarily in the Russian Kuban State University Hospital in Krasnodar. He did so even after he was barred from operating in Stockholm. But Karolinska did not seem at all to mind for him to continue his human experimenting in Russia. As the Asplund report notes:

“When the hospital identified Macchiarini as risk individual, he was excluded from the operating business. No notification was made to the National Board [the permit –granting agency Socialstyrelsen, -LS] -on the contrary, the hospital sought that his authorization to act as a doctor in Sweden is to be extended. The National Board granted the application”.

The poor hospital

The Karolinska hospital can hardly afford to pay damage compensations to the patients’ families at this time, as a source has indicated to me.  Some years ago a decision was made to build the “New Karolinska Solna”, an entirely new building complex for the Karolinska Hospital in the place of the old one. The money was supposed to come through the so-called Public-Private Participation scheme (see executive summary of the full scandal here). The leadership of the hospital dealt with the issue less than professionally (“on several occasions during the procurement process, the responsible healthcare authority proved to lack in competency and experience”), while the private partners were pocketing the public money. The main goal was to build Europe´s most impressive hospital: “form was prioritised at the expense of function”, the focus on most advanced therapies subordinated pedestrian aspects like general patient care.

The costs of New Karolinska Solna increased several times, the construction was delayed. As the consequence, the budget for the running activities of the hospital was severely downsized, new personnel is either not being recruited or recruited with poor work contracts, unpaid overtime work is standard.  At the same time, the hospital directorate made clear to their employees that the economic situation is not going to improve in the next few years, because of the huge burden in bank loans (allegedly tens of millions of Euro).

How will the costs of the Macchiarini scandal impact on the financially stricken Karolinska Hospital? Will the junior doctors and patients pay for the hubris, incompetence and greed of the hospital directors and senior clinicians?

The Google-translated full investigative report by Karolinska University Hospital is available here, with great thanks, also for highlighting, to Elizabeth Woeckner.

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Update 5.09.2016: please find my coverage of Karolinska Institutet investigation here.