INTER-ACTION. “We have a broad range of excellence and many prominent figures from around the world”. Research Day 2017 begins with these words from Erik Hanse, Assistant Dean of Sahlgrenska Academy and representative of one of the two organisers.
[Scroll down for more photos from the Research Day]
The second opening speaker was Ann-Marie Wennberg, Director of Sahlgrenska University Hospital. As one of the initiators of this event when it started one year ago, Ann-Marie Wennberg is pleased to note that there is a packed crowd in the Wallenberg Conference Center. It is a mixture of employees, many of whom are involved in both research and clinical work.
“I cannot stress how important researchers are in conferring knowledge on our clinical operations,” says Ann-Marie Wennberg before handing over to the presenters Research & Development Manager Anna Nilsdotter, SU, and professor John-Olov Jansson, Sahlgrenska Academy.
Surgery for obesity and diabetes, in addition to oral diseases, dominate the morning, where we also get to hear presentations of this year’s four holders of clinical research positions.
Surgery is effective against obesity
This year marks 30 years since Lars Sjöström started the SOS study with systematic follow-ups of those who had undergone obesity surgery, gastric bypass, which has proven to be the only really effective method for counteracting obesity. The SOS study, which owing to its size, design and long follow-up is unique in the world, primarily aims to investigate whether obesity surgery reduces mortality and morbidity. Over the years, 25 surgical clinics and 480 health centres have participated, and 2,000 patients have been included in the surgery group with as many in the control group.
“Thanks to the SOS study, the eyes of the world are today focused on Gothenburg when it comes to obesity research,” notes John-Olov Jansson.
One of today’s researchers in the field is associate professor Kajsa Sjöholm. She explains that there is much good news in the SOS study. Gastric bypass, which is currently one of the most common surgical methods, results in an average decrease in weight of 30 per cent at the 15-year follow-up.
“The control group patients weigh between 100 and 200 kilos, despite having undergone various medical treatments. Many have subsequently chosen to have surgery instead,” she says.
Some of the positive effects of obesity surgery:
- 30 per cent reduced risk of mortality in the surgery group compared to the control group. Cardiovascular disease and cancer are the most common causes of death.
- In total, approximately 30 per cent reduced risk of cardiovascular disease and 30 per cent reduced risk of cancer, however the latter being only true for women.
- 72 per cent of those that had type 2 diabetes at the start of the study were free of diabetes following the surgery. However, 15 years later, more than half developed diabetes once more.
- For those that did not have diabetes at the start of the study, there was a significantly reduced risk of developing type 2 diabetes after the surgery. There was more than an 80 per cent higher risk in the control group.
- Reduced risk of secondary diseases from diabetes, such as kidney disease, eye problems and loss of sensation.
Unfortunately there is also bad news in the form of alcohol problems, anemia and bone fractures. This is something that the researchers take seriously.
“Overall, there is so much good news that we should rather focus on prevention and better informing the patients before the operation instead of not operating at all,” concludes Kajsa Sjöholm.
Operations for obese children have now also been introduced within clinical study, explains Jovanna Dahlgren, professor of pediatric endocrinology. In all parts of the world, the same secondary diseases have been observed among children with obesity as among adults, aside from cancer. The cost to society is huge, with consequences into adulthood due to the significant risk that the obesity endures.
Ten years ago, the first operations were performed on children aged 13-18. A total of 81 children have received surgery within the so-called AMOS study. Most of these are girls with a BMI between 35 and 69. There is now ten years of data indicating that children who received surgery experience a lasting and significant weight reduction, while young people in the control group continued to go up in weight. Here, there is also a sharp drop in diabetes, decreased levels of blood lipids, inflammation and blood pressure. Post-surgery, the children’s fatty tissue is drastically reduced while their muscle mass is fortunately only marginally reduced – especially in the boys, notes Jovanna Dahlgren.
“We also see a bone mineral decrease despite vitamin D being administered, but we have not yet observed an increased risk of bone fractures. This is something we must observe over a longer time period.”
For the boys, the levels of testosterone are doubled already one year after the operation and remain at these normal levels. This is encouraging as the majority of boys who are obese have high estrogen levels and low testosterone, which can have metabolic and psychological consequences, notes Jovanna Dahlgren.
“It is important to get in early and break patterns in childhood so as to prevent diabetes. We have seen that through this substantial weight loss, the young people find it easier to access social environments where they integrate with peers and, among other things, form a family.”
At the same time, the patient’s mental state must be monitored after the operation. Suicide attempts and alcohol abuse have also been observed in this group. In other words, an operation is not a “quick fix”, but rather the teenagers need a lot of support from the treatment team following surgery.
“What we have observed is that most of the young people have experienced a significantly improved quality of life two years after the surgery. What remains is to study the long-term data and also see how the children born to the girls will be impacted by the mother’s surgery. We will chart the development of the pregnancy, the child’s growth and the subsequent risk of developing diabetes,” concludes Jovanna Dahlgren.
Surgeon Torsten Olbers, associate professor and chief physician, asks how many people know someone who has undergone obesity surgery. All hands go skywards. Around one per cent of Sweden’s population have received surgery for obesity. When the auditorium is asked if they have a positive view on the procedure, some are more hesitant.
Torsten Olbers shows a diagram with a curve indicating dramatic swings upward and downward, but with a clear long-term upward slope. It depicts the usual “dieter’s” path via various diets where the final result is often increased weight.
“What’s going on here? A lack of motivation? No, instead it’s the difficulty in maintaining weight loss. The body has a number of regulating mechanisms to revert to its ‘set point’”.
The explosion of knowledge in recent years concerning mechanisms shows that basically we are equipped with different conditions to maintain a normal weight.
“It involves signals from the adipose tissue, internal organs and the gastrointestinal system which communicate with the brain and control behaviour. ‘I eat just like my friend but I gain weight and he doesn’t’ – sound familiar?” asks Torsten Olbers rhetorically.
The twins test in the 70s was able to show that identical twins, raised in different families, exhibited weight development more similar to each other than to their families. Fraternal twins, who do not have the same genetic conditions, do not show similar weight development more than that observed in siblings in general.
“The research shows quite clearly that it is genetic conditions that largely inform an individual’s propensity for developing obesity.”
Many aspects of health and function improve with the sustained weight loss resulting from obesity surgery, says Torsten Olbers. Added to the aforementioned cardiovascular diseases, type 2 diabetes and high blood pressure are positive effects such as the reduction of asthma, sleep apnea, fatty liver, infertility, joint problems, psoriasis and rheumatism.
The gastrointestinal tract is the new area we need to study, this is what controls our behaviour. With operations we can change the basic mechanisms, asserts Torsten Olbers. But it is not just one mechanism, but several.
“Among post-surgery individuals we can also see altered preferences that often lean toward healthier food. And the intestinal flora changes. At the same time, the energy consumption is unchanged. In conclusion, it is the signals we are changing. It is not just the plumbing that’s important,” he says before adding:
“But there are likely to be late effects that we need to know more about. The healthcare services have perhaps not taken care of this group after the operations as well as we should have.”
Can a surgical procedure also work for type 2 diabetes? It is an interesting area of research, responds Torsten Olbers.
“Without going into details, we now have randomised trials with up to five years of follow-up which indicate a clearly superior effect from the addition of surgery in the case of type 2 diabetes compared with optimised medical treatment alone; even when the BMI is lower than 35 kg/m2. Quality of life is also improved.”
Metabolic surgery is the new concept, suggest Torsten Olbers. The question is whether it is we in the healthcare services who can propose these operations or if the patients actually requires them?
“Many who turn to the healthcare services for weight problems are met with the attitude of ‘you are responsible for your own weight’. I hope that we can reduce the stigmatisation and understand that nobody voluntarily chooses to be obese. There cannot be any contradiction between society implementing prevention initiatives and us needing to treat those who have developed obesity. I hope that we can use obesity and metabolic surgery wisely and that the patient receives clear information and adequate follow-up,” he concludes.
Physicians with higher research positions
Four researchers who have received higher clinical research positions this year presented their field of research. First up was Filip Bergquist, associate professor and specialist in neurology. He began by showing a picture filled with blue dots and one red dot so as to illustrate the basic problem in the treatment of Parkinson’s patients.
“The blue dots represent all hours of the year and the red dot is the one hour when we meet with the Parkinson’s patient.”
Parkinson’s disease is a degenerative disease which nevertheless can be effectively treated with drugs. Symptoms often vary over the course of the day and achieving the optimal result from the treatment requires paying attention to how the effects of the drugs vary throughout the day. This is difficult when you meet with the patient so rarely.
New technology allows us to address this. Filip Bergquist and his research team are working, among other things, with developing and evaluating the results of the Parkinson’s patient wearing sensors that register motion.
“We in Gothenburg were first to use these wearable sensors, so-called accelerometers, that are already available on the commercial market,” he says.
The aim is to adjust the medication accordingly and develop objective treatment goals. The research involves several projects, including one where several typesof sensors are sewn in to clothing, and another is examining a new form of preparation for levodopa.
Blood poisoning is more common in premature newborns
“We have previously talked about patients in the 200-kilo category, whereas my patients weigh 500-600 grams,” opens Anders Elfvin, chief physician and associate professor in neonatology.
Among the 20,000 children born in Västra Götaland each year, around 60-65 children are born before week 28 of the pregnancy.
Developments have taken great leaps and today it is possible to save the life of a child born in week 22-23. Survival rates among the most extreme premature cases are however still low; only 30 per cent. After week 25, there is a 90 per cent survival rate.
What Anders Elfvin and his research team have focused on is necrotising enterocolitis, NEC, and severe sepsis in premature infants. The research aims to identify patterns in the early bacteria flora that contribute to the onset.
“In the case of NEC, it’s not a large group; in 2016 we had six patients in Gothenburg. It is a severe disease that often presents between week 24 and 29 with necrosis and inflammation of the small and large intestine and with high mortality and disease among the survivors.”
Neonatal sepsis is markedly more common in newborns. 1-4 cases per 1,000 newborns viewed as an entire group, but much more common among premature infants.
Anders Elfvin mentions three projects he is involved in together with other researchers. They concern early factors for onset sepsis, where you look at the connection with early colonisation in the lungs, the skin, the oral cavity, the stomach and the intestine.
“It’s fashionable to look at the intestinal flora, but what is exciting is that the oral cavity’s early colonisation may have great significance,” he says.
One project is looking at the monitoring of children who have had NEC, specifically their osteoporosis, and another study is an epidemiological sepsis study.
Should pregnant women be given iodine supplements?
The thyroid gland is the focus of Helena Filipsson Nyström, who is a university hospital chief physician and associate professor of endocrinology. She presents two areas of research. The first one is Graves’ disease, which is an autoimmune disease that causes overactivity in the thyroid gland and leads to increased production of thyroid hormones, hypertension.
“Hyperthyroidism makes us angrier, more tired, you lose concentration and become less tolerant to stress,” explains Helena Filipsson Nyström.
The thyroid gland is dependent on iodine as an important building block. Thyroid dysfunction, including iodine deficiency, which leads to lower metabolism, can hopefully be measured in different ways, both through flows and volumes in the brain. This can then be linked to the neuropsychiatric outcome and to hormone levels.
In the case of Graves’ disease, patients with elevated thyroid hormone levels are treated medically so that the levels decrease and the patient feels well again. But some people do not feel entirely restored, despite the elevated levels being normalised.
“These people feel that they can no longer keep ten balls in the air. But who are they and how can we find them early on to give them treatment and support?”
The second research area is pregnant women and their intake of iodine. Generally speaking, today we eat less iodine than before since much of the salt we choose is not iodine enriched. But pregnant women need more iodine.
“Our hypothesis is that if a mother has an iodine deficiency during pregnancy, this affects the child growing up and in adulthood. Studies have shown that IQ drops by three points, which for an entire population is significant. So the question is whether we in Sweden should give pregnant women iodine supplements.”
Iodine levels in pregnant women are currently being measured. The initial data shows that the mothers have a slightly lower iodine level, but not so low that it would affect thyroid function.
A study has just begun where children in one group with mothers who have been given iodine are studied and compared to a group with mothers not receiving iodine supplements. These children will now be monitored at different ages.
“But clinical trials take time. The Graves’ study ends in 2018 and the study of pregnant women has just been expanded from 200 to 1,275 expectant mothers,” says Helena Filipsson Nyström.
Studying epilepsy in registers
Did you know that you are standing in Sweden’s epilepsy centre? This question is posed by the fourth researcher of those receiving higher clinical research positions – Johan Zelano. He goes on to say that Sahlgrenska University Hospital is one of Sweden’s largest centres for epilepsy care and the only Swedish hospital in a newly-formed European reference network for care providers with advanced epilepsy care.
Epilepsy can be congenital or arise from a brain injury, with stroke being the most common cause. The risk of developing epilepsy after a stroke is greater than previously thought, where a major stroke with bleeding in the brain cortex entails a greater risk than with minor injuries.
How is it for those who develop epilepsy after a stroke? Johan Zelano has studied the process of the disease using various registers. He took all individuals who had a stroke between 2005 and 2010 and monitored them with the help of the Patient Register. Approximately seven per cent developed epilepsy after a cerebral infarction and double as many following a hemorrhage. Using the Cause of Death Register it was possible to study survival rates, and the Stroke Register facilitated an attempt to adjust for the stroke’s degree of severity. Survival rates seemed to be worse for the stroke patient who developed epilepsy.
“A surprising finding as epilepsy after a stroke is considered to be easily treated,” says Johan Zelano.
A PhD project will attempt to identify the cause, whether it is a case of drug interaction or that the healthcare services are not sufficiently ambitious in ensuring that the patients are seizure-free.
The question of why brain injury sometimes causes epilepsy is still unanswered. It can involve both the nature of the injury and the circumstances when the injury occurs. There is also the possibility of a genetic vulnerability.
“But it is important to identify high-risk patients, and this is the goal of a study that uses biomarkers. Another study will use functional magnetic resonance imaging to look at whether nerve cell networks’ signaling is disrupted,” says Johan Zelano and concludes:
“Acquired epilepsy is becoming increasingly important. More and more patients are surviving advanced brain diseases, that often result in epilepsy.”
The mouth as a model for the body
Odontological research in Gothenburg has a prominent position globally, for example when it comes to oral implants and periodontal disease (periodontitis). The oral cavity is a well-defined and accessible environment as a research model for studies within infection, inflammation and tissue reactions. Johan Bylund, newly appointed professor at the Institute of Odontology, is one of the institute’s researchers who is not a dentist but rather a microbiologist and cell biologist. He gives an accessible description of the research conducted on a type of white blood cell, neutrophil, in the case of periodontal diseases. Johan Bylund describes the two ways that the neutrophils can destroy bacteria and shows a video where such a cell is seen chasing a bacterium with great precision.
When inflammation in the periodontal pockets becomes destructive, periodontitis arises, an inflammatory process that breaks down the tooth bracket and supporting bone. If the process continues for a long time, the tooth may be lost. Periodontitis is one of the most common diseases in humans.
Physician Per-Ingvar Brånemark discovered the principle of osseintegration during the 1950s and developed this discovery into an effective treatment with dental implants in Gothenburg in the 1960s and 1970s. Brånemark’s legacy can still be seen in the research on dental implants still being carried out here.
Professor Tord Berglundh notes that a dental implant is often a successful treatment, but that this can also give rise to complications, for example, an inflammatory process by the implant know as peri-implantitis. Peri-implantitis shares many similarities with periodontitis, but causes a more aggressive inflammation and a faster process. A new dissertation at the institute revealed that almost 8 per cent of patients with dental implants ten years after the treatment have lost at least one implant, and that almost 15 per cent of the patients had peri-implantitis. Patients with periodontitis run a greater risk of both implant loss and peri-implantitis.
Elective sessions
The afternoon offers a total of eight parallel seminars on the following topics; the cell’s power plant mitochondria, cardiovascular diseases, children with neurodevelopmental problems, obstetric care, new treatment methods introduced at SU, physical activity and cancer, infectious diseases, and how young people with a chronic illness are best transferred from pediatric care to adult care.
Heightened expectations regarding uterine transplantation
The final seminar of the day addresses Sahlgrenska’s leading role within research and clinical work in the field of uterine transplantation. Professor Mats Brännström describes how they have been very careful within the project not to take up healthcare resources. For example, the operations carried out have been performed during weekends and other times when the operating theaters are not needed for other activities, and with staff paid entirely with the research project’s funding.
Psychologist Stina Järvholm is also participating in the project and in her speech emphasised that there are actually four different people affected in the uterine transplant process: aside from the donor, there is also the recipient’s partner and the child that may result from the donation.
“We psychologists are normally brought in when there is a crisis. In this project we have been involved from the beginning,” says Stina Järvholm.
She also explained how those women who have had a transplanted uterus felt relief in returning to normal again after the organ was removed, something which goes against the idea that a woman without a uterus would not feel like a whole woman.
In total, six healthy children have been born as a result of the research on uterine transplantation at Sahlgrenska, and more are on the way. One of the women who participated in the study has even become a mother of two in the interim.
“Every child every born from a donated uterus has been born here in Sweden, within this research project. The project is ongoing, and we can see that expectations about the potential success of the method are rising,” notes Mats Brännström.
TEXT: COMMUNICATIONS OFFICERS KATARINA HALLINGBERG/ SAHLGRENSKA UNIVERSITY HOSPITAL AND ELIN LINDSTRÖM CLAESSEN/SAHLGRENSKA ACADEMY
PHOTO: FRANCIS LÖFVENHOLM
