Integrated Cardiovascular Function contributed with two posters and two discussions during the conference this year. Professor Otto Smiseth discussed the role of pressure-strain loops to assess left ventricular function and the head of the group Helge Skulstad partook in the discussion on guidelines for patients undergoing non-cardiac surgery, in which he also was a member of the task force.

Exposure during the conference is unique on the global stage. It provides a potential audience of 2.4 billion people with coverage ranging from Medscape to New York Times and Forbes. Inclusion in ESC 365 provides 4.1 million online views and the impact factor for the supplement of the European Heart Journal was 29.983 in the year 2020.
The 4500 abstracts that were presented in over 500 sessions under the duration of the conference thus gain worldwide long-term exposure for the group's professional profile, not to mention improvement in patient care and focus on future areas of research and development. 

A miniaturized accelerometer can be incorporated in temporary pacemaker leads which are routinely attached to the epicardium during cardiac surgery and provide continuous monitoring of cardiac motion during and following surgery. We tested if such a sensor could be used to assess volume status, which is essential in hemodynamically unstable patients. This novel method can facilitate continuous monitoring of the volemic status in open-heart surgery patients and help guiding fluid resuscitation. 

Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. 

Measurements of the left ventricular (LV) pressure trace are rarely performed despite high clinical interest. We estimated the LV pressure trace for an individual heart by scaling the isovolumic, ejection and filling phases of a normalized, averaged LV pressure trace to the time-points of opening and closing of the aortic and mitral valves detected in the individual heart. We developed a signal processing algorithm that automatically detected the time-points of these valve events from the motion signal of a miniaturized accelerometer attached to the heart surface. Furthermore, the pressure trace was used in combination with measured displacement from the accelerometer to calculate the pressure-displacement loop area.

It has almost become commonplace to state that islet transplantation has become an established beta-cell replacement therapy since the seminal publication of the Edmonton protocol. The significant improvement of outcomes reported has led to a multiplication of islet transplant centers and transplant procedures. In comparison to the 237 procedures performed during the 1990–1999 decade and reported to the now defunct International Islet Transplant Registry (ITR), 2,150 islet allotransplants have been reported to the Collaborative Islet Transplant Registry in the 1999–2015 period alone. 

Machine learning can reliably identify clinical and echocardiographic features associated with Cardiac Resynchronization Therapy (CRT) response and prognosis. The evaluation of both right ventricular size and functional parameters has pivotal importance for the risk stratification of CRT candidates and should be systematically performed in patients undergoing CRT.

In Januar 2021, Institute PhD fellow Erlend Skaga successfully defended his thesis Drug sensitivity and resistance testing of brain tumor stem cells for individualized functional precision medicine. 

Jan Egil Brattgjerd, a PhD fellow in the Biomechanics Laboratory headed by Lars Nordsletten, successfully defended his thesis Biomechanics of locking plates in femoral neck fixation in January 2021.

He described the biomechanical stability of femoral neck fracture fixation with special regard to the novel principle of interlocked pins in a plate developed to promote multi-directional stability and healing. Further aims were to analyse if patient safety requirements were met by investigating the novel implant´s strengths and weaknesses.

In May 2021 Institute PhD fellow John Moene Aalen successfully defended his thesis Insights into left ventricular dyssynchrony: Consequences for myocardial function and response to cardiac resynchronization therapy.

PhD fellow at the Experimental Cell Transplantation group Simen W. Schive successfully defended his thesis Islet allotransplantation in Norway and the potential of adipose tissue-derived stromal cells to improve islet survival in October 2019. Dr. Schive has worked under the guidance of Senior Researcher Hanne Scholz studying islet allotransplanted patients and the possible future methods for improving patient outcome.

This paper describes an ultrasound system to monitor cardiac motion using miniature transducers attached directly to the epicardial surface. Our aim was to develop both a research tool for detailed studies of cardiac mechanics and a continuous, real time system for peri-operative evaluation of heart function.

Cardiovascular disease is a leading cause of shortened life expectancy globally, with a 50% mortality rate five years after receiving the diagnosis of heart failure. Heart failure is commonly the endpoint of cardiovascular disease and the majority of patients perish from irregular heartbeat or pump failure. In both cases impaired calcium homeostasis and altered cellular electrophysiology are key underlying mechanisms.

The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression.

Despite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.

A new start-up company launched in May 2021 to commercialise innovations from Institute for Surgical Research.

Basic research in the laboratory of professor Håvard Attramadal at Institute for Surgical Research has uncovered the mechanisms of action of signaling molecules critically involved in fibrotic diseases. Based on these novel findings and advanced biotechnology research scientist Ole Jørgen Kaasbøll and professor Håvard Attramadal developed a novel drug with pan-antifibrotic actions that potentially may be used to target several fibrotic conditions including diseases affecting the kidney, lung and liver.

Three-dimensional (3D) echocardiography with multiplanar reconstruction (MPR) is used clinically to quantify the mitral annulus. MPR images are, however, presented on a two-dimensional screen, calling into question their accuracy. An alternative to MPR is an autostereoscopic holographic display that enables in-depth visualization of 3D echocardiographic data without the need for special glasses. The aim of this study was to validate an autostereoscopic display using sonomicrometry as a gold standard.

At first glance, left ventricular (LV) function may seem easy to understand, and most physicians are familiar with frequently used parameters such as ejection fraction (EF), stroke volume, and cardiac output. Although well known, these measurements do not necessarily provide a comprehensive measurement of LV function. - Smiseth, Aalen and Skulstad write in Heart failure and systolic function: time to leave diagnostics based on ejection fraction?.

Connective tissue growth factor (CTGF; now often referred to as CCN2) is a secreted protein predominantly expressed during development, in various pathological conditions that involve enhanced fibrogenesis and tissue fibrosis, and in several cancers and is currently an emerging target in several early-phase clinical trials. Tissues containing high CCN2 activities often display smaller degradation products of full-length CCN2 (FL-CCN2).

This report uncovers the novel finding that matricellular CCN2 is synthesized and secreted as a preproprotein that requires proteolytic processing to attain the capacity to elicit cell signaling responses. Furthermore, a homodimer of the active fragment, i.e. the C-terminal fragment comprising domains III and IV of CCN2, was shown to constitute biologically fully active CCN2.

In the most cited article published in European Heart Journal Cardiovascular Imaging these past two years, the authors of this multicentre study conclude that accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function.

The Vilhelm Magnus Laboratory celebrates its 40th birthday by arranging a symposium bringing together some of the most prominent members of the scientific society to discuss current advancements and future pathways for improved patient care.

Place: Runde auditorium, Domus Medica, Sognsvannsveien 9, Oslo
Date: 21st of October 2022

Demonstration of elevated left ventricular (LV) filling pressure is important for the heart failure (HF) diagnosis. In a joint recommendation from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI), it was proposed to use a combination of several echocardiographic parameters to evaluate left ventricular filling pressure.

Human pancreas-on-a-chip (PoC) technology is quickly advancing as a platform for complex in vitro modeling of islet physiology. This review summarizes the current progress and evaluates the possibility of using this technology for clinical islet transplantation.

Clinical trials are fundamental for therapeutic advances in GBM and according to the National Comprehensive Cancer Network, the best management of a cancer patient is in a trial. However, by current trial inclusion and exclusion criteria, only a selected group of patients can be considered eligible for trials. This bias not only restricts patients from receiving the best care, but also makes it difficult to extrapolate trial results to a real-world population. 

Tribune Therapeutics is a preclinical biopharmaceutical company building a promising pipeline of novel medicines to treat patients with a wide range of fibrotic diseases. Tribune Therapeutics was founded by Dr. Kaasbøll, Professor Attramadal and Mr. Vo Beiske together with HealthCap and Novo Seeds in 2020. Tribune Therapeutics has in-licensed an asset from Inven2, one of the largest technology transfer offices in the Nordic region.

In this study, we were able to identify for the first time a mutation-specific phenotype in MODY1 β-like cells facilitated by growing the cells in two different 3D environments and comparing the cellular and proteomic readouts to the 2D background. We were also able to suggest two specific molecular mechanisms whereby the two different 3D culture effects could be mediated. Each of these specific molecular mechanisms showed a dependency on the type of 3D context chosen. The cellular confinement in the alginate context helped to identify a metabolic phenotype with lower levels of glycolytic proteins, potentially affecting glucose sensing. The structural scaffolding in the AggreWell 3D context helped to identify a structural collagen-associated phenotype with irregular clusters, a unique proteome with lower levels of structural ECM proteins (laminins, collagens) as well as a functional readout.

How to determine response to CRT has been debated over the past decades, and it has been argued that similar to drug treatment, one may accept various treatment effects in the population treated. However, left ventricular remodelling with ESV reduction at more than 6 months is a strong determinant for all-cause mortality and cardiovascular mortality after CRT. 

A viable approach for optimizing the LV lead position could be to target areas where Td shortens the most. Shortening of Td could be used to confirm effective resynchronization when selecting pacing sites based on classical criteria for placement, like interlead distance, Q-LV, late mechanical contraction, and scar location.

Oslo University Hospital scientists are involved in developing a novel "organ-on-a-chip" technology for advanced drug testing, that may lead to improved personalized treatment. This project is broadly presented in a recent feature article in the major newspaper Aftenposten, entitled "Drug testing on mini-organs can reduce the use of laboratory animals", written by Steven RAy Wilsen (UiO), Carl Henrik Gørbitz (UiO), Stefan Krauss (Dept. of Immunology, OUS and UiO) and Hanne Scholz (Dept. of Transplantation Medicine, OUS and UiO).

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The Center for Heart Failure Research (CHFR) was established in 2002 and has since then promoted the integration of high quality research from bench to bedside. Center members have a broad range of expertise, covering state-of-the-art gene technology, protein function, integrative physiology in pathophysiological models and clinical studies. This collective knowledge and active research collaboration has resulted in more than 200 scientific publications each year.

The Annual Symposiums that began in 2003 have constituted an important platform for networking, introduction of up-and-coming academic talents, along with impressive research results, not to mention the presence of important international speakers shedding light on recent advancements in cardiovascular research.

Strengthening national research with the intent to promote scientific excellence has been an important mission for CHFR. Improving PhD programs and fostering young researchers is a way of reaching this goal. As part of this strategy, CHFR members initiated the establishment of the Norwegian PhD School of Heart Research (NORHEART) in 2012, together with key researchers from all major Universities in Norway.

The complete program from this year`s Symposium is available at heartfailure.no , while a report with pictures is provided by norheart.no.

Several researchers presented their latest studies at the annual Congress of European Society for Cardiology, the largest get-together of its kind. Elevating the Congress further this year was its conjunction with the World Congress of Cardiology, putting the spotlight on global cardiovascular health, highlighting differences in prevalence, clinical manifestations, prevention strategies, diagnostic modalities and management of cardiovascular diseases around the world, as stated on the ESC webpage.

Our research collaborator in Japan, assistant professor Katsuji Inoue, MD, PhD, presented two very interesting studies, the first suggesting that left atrial reservoir strain can be used to predict elevated pulmonary capillary wedge pressure, thus allowing discrimination between pre- and post-capillary pulmonary hypertension. The second study “Estimation of pulmonary artery pressure from right atrial strain and tricuspid regurgitation velocity” concluded that right atrial strain provides a semiquantitative measure of right atrial pressure, which can be used in combination with peak tricuspid regurgitation velocity to estimate systolic pulmonary artery pressure. This approach can be used as an alternative when the IVC method (estimation of right atrial pressure by echocardiographic evaluation of inferior vena cava diameter and collapsibility) is not available in cases with poor subcostal window.

Dr. Inoue also co-authored the study «Restricted left atrial motion as a result of atrial stiffening in patients with cardiac amyloidosis” that sought to determine whether left atrial (LA) reservoir strain with speckle tracking echocardiography could be used as a marker of LA stiffness in a derivation cohort. Furthermore, the hypothesis that LA reservoir strain could differentiate cardiac amyloidosis (CA) patients from hypertrophic cardiomyopathy (HCM) in an independent validation cohort was tested. The study concluded that LA reservoir function was fairly limited in patients with CA compared with HCM. Restricted LA motion might be related to atrial amyloid deposits or fibrosis, which potentially provokes atrial chamber stiffening.

The Inven2 idea prize 2019 was during the Cutting Egde Festival on October 24th awarded to a group of scientists from Oslo University Hospital for a new measurement system for assessing diabetic polyneuropathy. The researchers behind the idea are Christian Tronstad, Håvard Kalvøy, Ørjan G. Martinsen, Trond Jenssen, Jonny Hisdal, Inge Petter Kleggetveit and Ole Elvebakk. The award amounts to 250.000 NOK.

News article from inven2 (in Norwegian):
Og, vinneren er: en smartsokk for diabetikere!

Movie presenting the idea (in English):
Winner of idéprisen 2019 - Smart sock for preventing diabetic foot (via YouTube)

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GE Vingmed Ultrasound together with Oslo University Hospital, University of Oslo, KU Leuven, University of Maastrich, Jessa Hospital in Belgium and Medaphor were recently awarded 1.6 million euros for a Marie Curie project that will utilize artificial intelligence to diagnose a number of heart disorders. Several of the international partners in the new project have previously been central to CCI's international research collaboration. Over the years, the network and the exchange of skills have been strengthened through joint workshops, studies presented at both national and international conferences and, not least, the exchange of students and professionals.

During the ACC 19th Scientific Sessions Meeting in New Orleans in March, our visiting researcher Associate Professor Katsuji Inoue from Japan, presented two abstracts titled “Left Atrial Strain as a Surrogate Marker of Atrial Chamber Stiffness” and “Reduced Left Atrial Reservoir Strain at Rest Predicts Elevated Left Ventricular Filling Pressure During Exercise”, where the latter was selected as a moderated poster under the non-invasive imaging session in addition to being introduced in the Echocardiography Highlights Session at the ACC 2019. 

Center for Heart Failure Research (CHFR) invites to a workshop on Diastolic Function in Heart Failure on Wednesday 7th of November at Ullevål Hospital, starting at 12'00 o'clock.
Holding the key note lecture will be Professor Frank A. Flachskampf, MD, PhD from University of Uppsala, Sweden.
Professor Flachskampf is part of a world-renowned clinical research team in ischaemic heart disease and his talk will address how imaging reflects pathophysiology in diastolic function assessment.
The final talk of the day will be by Associate professor Stig Urheim, MD, PhD from Haukeland University Hospital. His talk is titled "Exercise intolerance in heart failure patients with preserved EF (HFpEF) - not only diastolic impairment".

Sign up for the workshop     

Read the program

The Research Council of Norway reports that Norway exceeds two per cent share of Horizon 2020 contribution for the first time.  Figures from the EU show a steady increase in the number of Norwegian projects with successful proposals. “It would appear that Norwegian applicants have cracked the code and that we’re now surging ahead,” states John-Arne Røttingen, Chief Executive of the Research Council.
Of the more than 10 mill Euro going to Norwegian health authorities Oslo University Hospital receive 7.9 mill Euro and Helse Bergen 1.6 mill Euro.

Welcome to the next Oslo University Hospital (OUH) research seminar entitled
Tissue engineering and regenerative medicine

Time: Monday, March 5th, 2018, 14:30 – 16:00
Place: Red Auditorium, Rikshospitalet, Sognsvannsveien 20, Oslo

Speakers: Joel Glover, Kamal Babikeir Eln Mustafa, Shadab Abadpour, Rick Siller

Six research groups were awarded for their excellent papers published during the first half-year of 2017 during a ceremony on December 16th. Each group received NOK 50.000 for use in further research. The prize winners gave short presentations of the main findings in their respective articles.

The six selected articles are of especially high quality, and they present important finding on both-short and long-term scales. The works reflect the good quality and the interdisciplinarity that characterises several research environments at Oslo University Hospital. The research is a fundamental condition for the institution to maintain and strenghten the quality in the patient treatment.

In order to stimulate excellent research and draw attention to the hospital's extensive research activity, Oslo University Hospital reward outstanding publications regularly.

Every half-year, six of the very best papers authored by scientists working on the hospital (first or last author must be affiliated to OUS) are selected. The nomination takes place through the research panel of each division. The final selection process is performed by an external committee.

The award winners are ranked equally.

Welcome to the next Oslo University Hospital (OUH) research seminar entitled "Medical imaging in cardiac research".

Time: Monday, October 10th, 2016, at 14:30 – 16:00.
Place: Green Auditorium, Rikshospitalet, Sognsvannsveien 20, Oslo.

Speakers: Ivar Sjaastad, Emil Espe, Einar Hopp, Thor Edvardsen and Espen Remme.

The Institute for Surgical Research celebrates it's 50 years anniversary on Thursday 13 October 2016. The seminar takes place at Oslo University Hospital, Rikshospitalet, in Store Auditorium, starting at 10.15.

Lecturers are Håvard Attramadal, Hanne Scholz, Gunnar Tufveson, Pål Dag Line, Lester Lau, Otto Smiseth, Thor Edvardsen, Iver A. Langmoen, Krishna Bhat, and Lars Nordsletten.

See the program

A project initiated by post doc Einar Vik-Mo and professor Iver Langmoen from the Department of Neurosurgery at OUS has drawn interest from Norwegian media. The major newspaper Aftenposten has recently presented his project in a feature article entitled "Norwegian physicians tailor make chemotherapy to each tumor".

Prospective isolation of tumour initiating cells is possible using tumour specific antigens. Vik-Mo, Langmoen and collaborators are currently working on the isolation and characterization of such tumour initiating cells using primary cell cultures, both as floating neurosphere assays and adherent cultures, and combining this with FACS and MACS to prospectively isolate the putative tumour initiating cells.

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