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PD Dr. med. Christiane Sokollik was invited to the 39th Annual Meeting of the Society for Paediatric Gastroenterology, Hepatology and Nutrition in Essen to give the lecture "Best of Gastroenterology 2023". She was to present her "Oscars" for studies and scientific achievements in the field of gastrointestinal diseases.

We wanted to know from PD Dr. med. Sokollik which studies she selected and why.

Answer from PD Dr. med. Sokollik:

Thank you very much for these questions. Studies must not only be conducted, but the results must also be communicated to patients and doctors. "Best of Gastroenterology 2023" is a great format for this. The target audience was doctors who treat children and adolescents with gastrointestinal diseases. They don't always have enough time to read scientific studies and papers in their day-to-day work, especially studies that deal with basic research. I have therefore selected three studies that produced both new, directly applicable results and studies that point to the future.

• The first study showed that a new drug can help children and adolescents with severe constipation. I am curious to see whether it will prove itself in everyday clinical practice in the future.
  The study: https://www.sciencedirect.com/science/article/abs/pii/S2468125323003989
   
• In the second study, scientists found out why a drug does not work well in some patients with chronic inflammatory bowel disease. The intestinal bacteria (= microbiome) of these patients were able to produce enzymes that metabolize the drug and thus render it ineffective. This finding has far-reaching consequences - will we soon be able to screen patients' gut bacteria for these enzymes? Can we perhaps even render these enzymes "harmless“ in the future?
  The study: https://www.nature.com/articles/s41591-023-02217-7
   
• The third study deals with the use of artificial intelligence (AI) for the benefit of patients. It showed that AI-generated explanatory texts on gastrointestinal endoscopy are easy to understand and scientifically correct. AI therefore offers great potential to simplify communication between doctors and patients.
  The study: https://www.gastrojournal.org/article/S0016-5085(23)00704-7/fulltext

The intestinal microbiome is associated with health and many diseases. What is less known is that the microbiome as an organ produces various substances that not only have an influence on the intestine and the intestinal bacteria, but also on the entire human organism.
One example of a molecule produced by intestinal bacteria is D-lactate. The special thing about D-lactate is that humans do not have an enzyme to metabolize it. Therefore, we took a closer look and analyzed the role of D-lactate in gastrointestinal diseases. Based on our results, we call for D-lactate to be further investigated in diseases and to have a potential role as a biomarker for gut health in the future.
The study: https://www.mdpi.com/2227-9067/10/6/945

Question from Emanuelle M. (name changed by editor), age 14 with IBD-unclassified, a subtype of inflammatory bowel disease:

«It bothers me that I don't know if I have Crohn's disease or ulcerative colitis. Can't artificial intelligence help give me more certainty?»

We pass Emanuelle's question on to Dr. med. Aurélie Pahud de Mortanges. She is a physician and a specialist in machine learning. We just published a study with her on "Machine Learning in Antibody Diagnostics for Inflammatory Bowel Disease Subtype Classification" in the medical journal Diagnostics.

Answer from Dr. med. Aurélie Pahud de Mortanges: «Dear Emanuelle, in Machine Learning, we teach computers to recognize patterns based on collected data and apply them to new tasks. Machine learning is a subfield of artificial intelligence. In our work, we investigated whether it is possible to further improve diagnostic confidence in inflammatory bowel disease using machine learning. Crohn's disease and ulcerative colitis can already be well distinguished by our algorithms, and now we are working on also being able to predict whether IBD-unclassified has underlying or developing Crohn's disease or ulcerative colitis. Some patience is still needed, but the more data we can collect from affected individuals, the better our algorithm will become. We promise to keep at it so you can be more certain about your diagnosis.»

The intestinal microbiota is an important component of our body, but little is known about the development. However, the first years of life are crucial, which is why we are investigating the maturation of the infant gut flora in the BeBiCo study. Since the first birth in May 2020, a total of about 8,000 samples have already been collected. After 3 years, the first interim results are now available.

Question to Prof. Dr. Stephanie Ganal-Vonarburg, biologist and one of the leaders of BeBiCo: "What are the most exciting discoveries you have made so far?"

Professor Ganal-Vonarburg's answer: "Thanks to the many samples, we have already been able to observe many interesting things. We can show that the intestinal flora changes a lot over the first year of life. We have also found bacteria in the early childhood intestinal flora that are no longer found or almost no longer found in adults (Actinobacteria, Deferribacteres). Now the next step is to analyze the individual stool samples in detail in order to find out more precise information about the composition of the intestinal flora of the individual child. How important is the nutrition of the child and the mother?  When analyzing the mother's milk, we were able to see that a very specific series of immune cells, the so-called T-lymphocytes, are found in unsuspected numbers in the mother's milk. In the next few years, we will focus on finding out how exactly the immune cell composition of breast milk affects the development of the infant gut flora and infant immunity. Our goal is to recruit 250 mother-infant pairs by 2026. Contact us if you are interested in participating."

«Connect 4 children» (c4c) is a big European cooperation network that aims to facilitate the development of new drugs and other therapies for children and adolescents. Experts from all European countries advise research groups and pharmaceutical companies on the planning of multinational, high-quality clinical trials. The c4c project is funded by the European Union.

We actively support c4c by having PD Dr. med. Christiane Sokollik as the Swiss representative for pediatric gastroenterology.

Question to Mrs.PD Dr. med. Sokollik: «Why are you involved in c4c?»
Answer: «Children are not "little adults" and treatment strategies in adults cannot simply be transferred to children and adolescents. Therefore, clinical studies are needed that include the whole complexity of treating children. My motivation is that children and adolescents should also benefit from medical developments and advances at an early stage.»

Contact us​​​​​​​ if you would like to learn more about our commitment to research in pediatrics.

Question from Jan T (name changed by the editors), age 10, suffering from inflammatory bowel disease and autoimmune hepatitis:

"I saw a poster about rare diseases. Do I have a rare disease too?"

Answer from Prof. Jean-Marc Nuoffer, Head of the Rare Diseases Center, Inselspital, University Hospital Bern:
"Dear Jan, a disease is considered rare if only 5 out of 10,000 people have it. To date, about 7000 rare diseases have been described in the world. Often a rare disease is congenital. It is estimated that in Switzerland half a million people suffer from a rare disease, which is about 6% of the population. Whether a disease is rare or not can be looked up in the public database Orphanet (https://www.orpha.net/). Inflammatory bowel disease is not a rare disease, although few people your age have inflammatory bowel disease. In Switzerland, about 1 in 350 people have inflammatory bowel disease, but most are adults. Autoimmune hepatitis is rare, even in adults, and is therefore considered a rare disease."

Response from PD Dr. med. Christiane Sokollik:
"Dear Jan, in order to better help you and other children with a chronic disease in the future, we participate in the Swiss Cohort for Inflammatory Bowel Disease and the Swiss Cohort for Autoimmune Hepatitis. We are also involved in the European Network for Inflammatory Bowel Diseases and the European Network for Rare Liver Diseases (ERN RARE-LIVER; ERN Hepatological Diseases - RARE-LIVER). Thanks to these cohorts and networks, we can share knowledge across Europe to improve treatment for childhood (rare) diseases."

We congratulate Katharina Guilcher, MD, and Leyla Wenk, MD, for their contributions at the annual conference pädiatrie schweiz 2022 .

The lecture by Katharina Guilcher was very well attended and a lively discussion ensued on the topic of "Complementary and alternative medicine: Use in children and adolescents with inflammatory bowel disease". The definition of complementary medicine alone is difficult. We doctors are often not aware of the alternative treatment methods our patients receive. However, knowledge about this would be very important so that we can include it in our treatment and recognize and avoid undesirable interactions in time. Gaining more clarity here is the scientific focus of Ms. Guilcher. 

Leyla Wenk presented an interesting case about the connection between vitamin B12 and pancreatic function from her consultation.

Question from Sebastian M. (name changed by the editors), age 14:

«I read in the newspaper about the hepatitis outbreaks in England and the USA. Why do the doctors not yet know what the cause of the disease is?»

Answer from PD Dr. med. Christiane Sokollik, Head of Research Pediatric Gastroenterology, Hepatology and Nutrition: 
«Exactly, in Europe and also in America, there have been clustered cases of acute hepatitis in young children. To date, no cause has been found. The known viruses that cause acute viral hepatitis (hepatitis A, B, C, D, and E) have not been detected in any of the cases. Therefore, until now we do not know what is the cause of these outbreaks. For this reason, all doctors who treat children with hepatitis have been contacted. We in Bern have also been asked to report any child with similar symptoms. The health authorities and international organizations (such as the WHO) create overviews from these reports (see picture) and can then approach doctors with further questions.

The first step is only to find out how many children are affected. Subsequently, scientific questions are developed to find out what exactly is the reason for the hepatitis outbreak. The close cooperation between the countries will allow the cause to be found more quickly and hopefully provide patients with a good therapy quickly.»
 

Another question from Mirella A. (name has been changed by the editors), 15 years, suffering from autoimmune hepatitis, participant in the AILD-cohort:

«Dear Mrs Terziroli, thank you very much for your answer. I would be very interested to know how you analyse my blood. Do you analyse it in a laboratory?»

Answer from PD Dr. med. Benedetta Terziroli: 
«Dear Mirella, that's right, I'm analysing your blood in our laboratory. In the picture you can see me sitting in front of a clean bench called a 'hood'. The hood prevents your blood from being contaminated by external factors. That's why I also wear gloves, a white lab coat and sit in front of a glass pane. The pipette in my hand is also very important for my work. With it, I can measure tiny amounts of liquid very precisely. With the pipette, I can drop small amounts of your blood onto the coloured culture media. This helps me to analyse your blood in detail and to understand how your immune system has reacted to the vaccination. We also offer work experience placements in the lab. If you are interested in working in the lab, you are very welcome to ask your doctor about it.»

Recently, I had an introduction to simple linear regression in the "Statistics and Epidemiology" course I took. Linear regression is used when there is an interest in the relationship between two variables. Professor Messerli used this method to find a possible relationship between chocolate consumption and Nobel Prize awards. You can see the result of his study in the picture on the right side. 

This plot shows a strong correlation between chocolate consumption (per capita and year) and the number of Nobel Prize awards per inhabitants in different countries.
Switzerland has the highest chocolate consumption AND also the most Nobel Prizes per inhabitants. Therefore, nothing stands in your way to enjoy chocolate at, during and even after Christmas!

(For the exact analysis, also regarding correlation and causation, we refer to the source of this blog entry at the bottom).

We wish you a Merry Christmas and a Happy New Year!
Gia Thu Ly
and the whole Pediatric-Gastroenterology-Research-Team

^{Messerli FH. Chocolate consumption, cognitive function, and Nobel laureates. N Engl J Med. 2012 Oct 18;367(16):1562-4. doi: 10.1056/NEJMon1211064. Epub 2012 Oct 10. PMID: 23050509}

Question from Mirella A. (name has been changed by the editors), 15 years, suffering from autoimmune hepatitis, participant in the AILD-cohort:

«With friends I discussed to get immunized against Covid-19. But I have a liver disease. Will the vaccine effect me?»

Answer from Gia Thu Ly, study assistant:
«Dear Mirella, it is great that you are thinking about to get vaccinated against Covid-19. Since you have a rare condition, it is important to ask about possible effects on your disease. I will pass on the question to PD Dr. med. Benedetta Terziroli. She is the prinicipal investigator of the AILD-cohort where you are a participant. She actually is performing a study to investigate the effect of the vaccine on the liver.»

Answer from PD Dr. med. Benedetta Terziroli:
«Dear Mirella, thank you for your question! I often get this question by my adult patients as well. The vaccine provokes a strong response by your immune system. When you get in contact with the virus after the vaccination, very precise weapons are ready to fight against the virus and prevent that you become very sick. 
Your liver disease is special as your immune system attacks your liver for reasons we do not know. It seems that it thinks that your liver cells, called hepatocytes, are enemys and fights against them. When you get vaccinated we will collect some blood from you and I will investigate the response of your immune system to the vaccine. Up to now there is no certain knowledge that people with your disease have an increased risk from the vaccine. Nevertheless, if you get infected, the virus itself elicits a very strong immune response, which may be harmful for the liver. In summary, I recommend that you get vaccinated, since the virus is much more dangerous compared to the vaccine.»

We are pleased to announce that the programm for the 20th Heiner-Brunner Seminar has been finalized. There will be hands-on workshops, lectures, seminars and opportunities to exchange ideas with the other participants and speakers. We would like to thank already all speakers and the organization team from eventlab.

Question from Noah P. (name has been changed by the editors), 14 years, came after his first meeting with a master student to me and asked:

«What exactly is a master’s thesis?»

Answer from Gia Thu Ly, study assistant:
«Dear Noah, we supervise several medical students here in the pediatric gastroenterology clinic for their master's thesis. I'll pass the question on to Joachim, one of our master students.»

Answer from Joachim Schaad, Master student of the celiac disease study:
«Dear Noah, in medical school we have exams about diseases, but we also work on a scientific project/study, this is our master's thesis. I was allowed to choose a topic and I chose celiac disease in children. First, I read about the disease. Then I searched the hospital database for information about children and adolescents with celiac disease. The data are anonymous. I want to know, how diagnosis and treatment of these children and adolescents can be further improved. In this way, I am contributing to medical research and help patients already as a medical student. And the good thing about the master's thesis is that I'm accompanied by doctors throughout the whole time and they help me with any uncertainties, like coaches in the floorball club or teachers in piano lessons.»

We would like to congratulate Emilie Kaufmann on the publication of her doctoral thesis in the Swiss Medical Forum. In this article we would like to briefly introduce you to her case study.

A six-week-old girl presented to the hospital with vomiting and diarrhea. Initially, the most common cause was thought to be "stomach flu". But when diarrhea persisted, the girl had to go to the university hospital to look for the cause. A gastroscopy was performed (a camera was used to look into the stomach and intestines and tissue samples were taken). This revealed changes that pointed to an infection with the cytomegalovirus (called 'CMV' for short). Thus, the diagnosis of a CMV infection in the stomach and intestines was made. Until the infection was cured, the girl had to stay in hospital for another 6 weeks, but recovered well and was able to go home healthy.

In her doctoral thesis, Emilie showed doctors how such patients must be clarified and which therapies are available.

Question from Jasmin L. (name has been changed by the editors), 11 years old, suffering from Ulcerative Colitis, participant in the IBD cohort:

"What are you looking for in my blood? My intestines are sick, after all."

Answer from Gia Thu Ly, Study Assistant:
"Dear Jasmin, when a blood sample is taken at the regular annual check-up in the consultation, some additional blood is drawn for the IBD cohort study. In your blood we were looking for PR3-ANCA. I will pass your question on to Mr. Horn, since he did the PR3-ANCA determination."

Answer from Dr. phil. nat. Michael Horn, Head of Immunserology:
"Dear Jasmin, you have surely been vaccinated? With a vaccination your immune system learns to fight off foreign bacteria or viruses. That is the main task of your defense system: to protect you from all "evil". Unfortunately, there are also diseases in which the defense system is directed against your own body or against certain cells in the body. And this is exactly what happens in Ulcerative Colitis. 

Thanks to this study, in which you are also participating, we have been able to determine that patients with Ulcerative Colitis form antibodies much more frequently against a protein called PR3-ANCA, which is found in certain immune cells. We were able to show that the determination of these antibodies can simplify the diagnosis of Ulcerative Colitis. In addition, we can look under the microscope to see where these antibodies bind in the immune cells. They show a very specific pattern because the protein PR3-ANCA attaches around the nucleus of the cell. In the picture, you see a green ring, inside the ring is the cell nucleus. If your pediatrician gets this result, she knows you have Ulcerative Colitis."  

We would like to congratulate Medea Salzmann on her lecture at the GPGE. In her MD thesis, Medea deals with adverse events in drug therapies in chronic inflammatory bowel diseases. 

Her work entitled "No difference in adverse drug events in pediatric Crohn's disease versus ulcerative colitis patients" was exceptionally selected for a 15-minute presentation at the 36th Annual Meeting of the GPGE (see picture). This is a great appreciation and shows how important this topic is for patients and the treating physicians.

Question from Peter Z. (name has been changed by the editors), 12 years, suffering from Crohn's disease, participant in our Campylobacter Concisus Study:

"What happens to my stool which I collected for the study?"

Answer from Gia Thu Ly, Study Assistant:
"In the Campylobacter concisus study, we are examining the stool of children with inflammatory bowel disease. We want to find out whether a Campylobacter concisus infection can lead to a flare-up of the disease in children and adolescents with inflammatory bowel disease. The stool samples are analyzed at the Institute for Infectious Diseases (IFIK), so I will pass the question on to our co-investigator Dr. Carlo Casanova."

Answer from Dr. Carlo Casanova, Deputy Head of Department Bacteriology/Mycobacteriology:
"Dear Peter, your stool sample is spread on a special Campylobacter culture medium in a plate. This plate is artificially heated in a cabinet so that the bacteria in the stool sample multiply. If there are Campylobacter bacteria in the stool, they will grow in small circles, so-called colonies, on this nutrient plate (see picture). There are various bacteria that belong to the Campylobacter family. However, we are only interested in Campylobacter concisus. Therefore, the grown colonies have to be examined with a special method, mass spectrometry. With this method we can find the Campylobacter concisus bacterial colonies. Campylobacter concisus cannot be detected in all stool samples. If cultivation of the bacteria is successful, they can then be examined in more detail."

To bridge the time until we can resume our workshops «Helden des Darms» (see news blog June 2020), we will launch a new series: questions and answers (Q&A). Here we will answer questions about our research in the pediatric gastroenterology.

Questions from our patients and study participants will be collected and answered. Please feel free to send us your questions.

We are happy to announce that PD Dr. med. Christiane Sokollik was elected as president of the 20th Heiner- Brunner- Seminar. She will be supported by Dr. med. Franziska Righini-Grunder from the Children’s Hospital Luzern. The Heiner- Brunner- Seminar is the biggest educational event for German speaking pediatric gastroenterologists and an integral part of the academy of the Society for pediatric gastroenterology and nutrition (GPGE). It welcomes 200 participants from Germany, Austria and Switzerland every year.

The importance of our gut bacteria (microbiome) for our health is becoming increasingly apparent. At birth, a newborn suddenly comes into contact with a whole host of bacteria and other microorganisms in the environment. This is the beginning of the maturation of the microbiome, which is consolidated in the first years of life and is difficult to influence later. Over time, each person develops his or her own personal microbial fingerprint.

In Bern, we investigate the changes in the intestinal bacteria during the first years of life. We are asking which factors influence the development of our intestinal bacteria or whether certain diseases can be identified from the composition of the intestinal bacteria. In order to answer these or other questions. The intestinal bacteria present in the stool are determined at regular intervals. In this context, Stephanie Ganal, professor at the University of Bern, is investigating the influence of breast milk on the microbiome. She presents her work in the SRF Einstein documentary «Besser leben dank gesundem Darm». Our research group is also working on the study as co-investigators.

If you would like to learn more about this work, please feel free to contact us.