“A single lab value buried inside 6 kilograms of data”: Solving rare medical mysteries

He’s the German equivalent of “House M.D.” Every day the most difficult medical cases land on his desk, from patients in a desperate search for diagnosis. In this interview, Prof. Dr. Juergen Schaefer, head of the Center for Undetected and Rare Diseases at the University Hospital of Marburg, explains the detective work involved in complex medical cases.

Foto: Sarah Pflug

What makes a center for undetected and rare diseases different from others?

Prof. Juergen Schaefer: We do nothing different from other doctors throughout Germany and we are not better doctors — and certainly not ‘House M.D.’s. However, the luxury we have here at the University Hospital in Marburg is that we are given the freedom and time necessary to work through difficult cases meticulously. We also have laboratory and IT support, which is very important for us. If we have diseases in front of us that have been described worldwide maybe once or twice, then we need powerful IT support to provide us with data that may have been published, for example, only once somewhere in South America.

Artificial intelligence also plays a role here, as it will greatly support our activities in the foreseeable future. The e-health initiative, which was already launched by Stefan Gruettner as Hessen’s Minister of Social Affairs and is now being consistently pursued, also plays a major role for us here. The fact that we have been able to establish a special professorship for artificial intelligence in medicine in Marburg this year with the world-famous AI pioneer Prof. Dr. Martin Hirsch is also associated with a lot of hope for these rare diseases.

We also have the advantage that we have a clinical research laboratory and low-threshold access to almost all research groups at our university, so that we can use them to solve even quite complex problems. If in this modern world humans can fly to the moon, surely we should also be able to find out what health condition a person suffers from. We also realize just how important our diagnostics are, both for the person concerned and for society as a whole, especially in times of corona. However, whether such facilities like our ZusE (Center for Unknown and Diseases) can survive in the long term stands or falls with their establishment in care plans and fair reimbursement of costs by the funding agencies. Even after 7 years of successful ZusE work, this is still not the case, although we and also the politically responsible persons know how important such facilities are for many people.

"We are probably the only university hospital in the world that has established a center based on a course of lectures."
Prof. Dr. Jürgen Schäfer

How did the center come to be?

Prof. Juergen Schaefer: It all came to us rather by chance. Rare diseases have always interested me. That’s why I worked as a scientist at the National Institutes of Health (NIH) in the USA for four years, and I am glad to be able to continue my research at an excellent university hospital. Here, I have the good fortune that as an endowed professor of the “Dr. Reinfried Pohl Foundation.” I also have the freedom and support to develop and try out innovative teaching concepts. Basically, everything started with a small lecture class entitled “House M.D. revisited – or: Would we have cured the patient in Marburg, too?” In this seminar, I use the TV series “House M.D.,” which is popular with students, as a door opener, so to speak, to get them excited about rare diseases and diagnostic strategies. 

For this teaching format, which we have also scientifically evaluated in the meantime, I was awarded the “Ars Legendi Prize,” the highest teaching award for medical teachers, by the Medical Faculty Association (MFT) and the German Donors’ Association of Founders in 2010. However, this somewhat unusual seminar was not only well received by the students; it also aroused enormous media interest. After I was suddenly named the “German House M.D.” by the German Medical Journal and was awarded the “Pulsus Award” as Doctor of the Year in 2013, I received inquiries from desperate patients from all over the country who were in urgent need of help. Our management at the time, with Prof. J. Werner, H. Thiemann and G. Weiss, supported me in this situation to the best of their ability and then founded the Center for Unrecognized Diseases (ZuK; now known as the ZusE) at Marburg’s University Hospital.  I am still grateful today for the fact that I was not left alone with thousands of inquiries, but that out of necessity a center was founded which is unique in Germany. The fact that a completely new kind of center was founded at a renowned, almost 500-year-old university clinic just because of a class for medical students is probably unique in the world.

"Hessen is an extremely strong region for research."
Prof. Dr. Jürgen Schäfer

How many patient enquiries do you receive?

Prof. Juergen Schaefer: We receive about 1,000 patient inquiries per year. In total, we have received almost 9,000 patient inquiries. Some of these inquiries are easy to solve, but other inquiries take us days to get through. We spend a lot of time reviewing findings. Because of the large number of inquiries, we must insist that the inquiries are sent to us by the treating physicians with a description of the exact problems. A detailed anamnesis, i.e. an exact collection of the patient’s history, is an essential part of our work. The ZusE team meetings, during which we discuss the most complicated cases within a group of experienced colleagues, have a very important function for us. The team then includes almost all the main areas of expertise – from general medicine, laboratory medicine, cardiology, endocrinology, nephrology, neurology, etc. to psychosomatics, which plays a very important role in our work. Sometimes external doctors send us several files packed full of medical letters and findings. Then we sometimes need days alone for processing because we have to look at every single laboratory value; sometimes it is really only  single laboratory value in six kilograms of paper which provides the solution for the disease, and this must not be overlooked. But because of this meticulous work process, the waiting times are also unbearably long, and this is a great burden both for the patients and for us. We also ask patients to first contact the university hospitals close to their home or nearby centers for rare diseases that can be found in the SE Atlas. Especially for our work, an electronic patient file, which allows a quick overview of all findings collected so far, would be a great help.

Prof. Dr. Jürgen Schäfer, Foto: transQUER

Which patient cases have left a particularly strong impression on you? 

Prof. Juergen Schaefer: Cases that really bother me are patient fates that could actually have been prevented if the correct diagnosis had been made early enough. One patient has remained in vivid and painful memory. He came to us almost blind and deaf, with extreme heart failure, and he was actually terminally ill. At the end of the examination it turned out that the cause of his illness was poisoning from a broken femoral head prosthesis. He had received a metal femoral head prosthesis as a replacement for a broken ceramic prosthesis. The remaining ceramic splinters destroyed the metal head and thus a severe metal poisoning occurred, from which our patient (and subsequently many others) almost died. After the defective femoral head prosthesis was replaced, the patient fortunately recovered to some extent and survived this life-threatening situation. Such fates, which endanger the lives of patients and which fundamentally should never have happened in the first place, touch even veteran hospital doctors, who have actually seen almost everything. 

Why is such a center so successful in central Hessen in particular?

Prof. Juergen Schaefer: There are also such centers in other federal states that are no less successful. However, I would like to point out – also in my capacity as ‘Ambassador of Central Hessen’ – that Hessen, and especially Central Hessen, is an extremely strong research region in the field of medicine. Central Hessen is not only located in the heart of Germany, but it also has the highest density of students in Germany with over 71,000 students at three universities – Justus Liebig University, Philipps University Marburg and the Technical University of Middle Hessen. We have unbelievably great focal points in our region, such as an ‘Excellence Cluster Cardio-Pulmonary System’ in Giessen, a high-security laboratorylevel S4 – for highly pathogenic viruses in Marburg, several Max Planck Institutes, collaborative research centers and a strong research-based pharmaceutical and optical industry. In addition, the University Hospital Giessen and Marburg (UKGM) is one of the largest university hospitals in Germany. There are many well-known doctors and renowned researchers working in the region, and since university medicine also fulfils the care mandate of a municipal hospital, patients have always been the focus of attention here and are treated at the highest level.

We also have a great network with the Technical University of Middle Hessen, which means that we have a local network of structures that you have to look for a long time elsewhere in Germany. Our advantage of this is that – unlike in many mega-cities, which of course also have such structures – we have a close network in Central Hessen, open doors and a great willingness to help everywhere. In addition, we have traditionally had very close links with many companies, such as CSL Behring, in the fields of research and therapy. The fact that more cooperation, rather than competition, between universities is also being promoted politically is particularly beneficial to our region – it is up to us to make the best of it.

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