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News Article | May 22, 2017
Site: www.eurekalert.org

Earlier discovery of cancer and greater precision in the treatment process are the objectives of a new method developed by researchers at Sahlgrenska Academy and Boston University. Investments are now being made to roll out this innovation across healthcare and broaden the scope of the research in this field. "We can screen at-risk patient groups, and we also plan to spot the cancer patients who are relapsing so that we can adapt their treatment," says Anders Ståhlberg, docent in molecular medicine and corresponding author for two articles about the method. The technique was created based on the fact that people with cancer also have DNA from tumor cells circulating in the blood, molecules that can be discovered in a regular blood sample long before the tumor is visible via imaging such as tomography, MRI, X-ray and ultrasound. The researchers have now increased the sensitivity of detecting tumor DNA in blood thousand-fold by eliminating the background noise from the measurements using "DNA barcoding". "One of the benefits of the technique is that it makes use of available instrumentation, which means it can be applied in most labs. We are not first in the world to show that barcoding concept works, but in our case we have developed a fast and flexible method that is simple, flexible and cost-effective to use," says Anders Ståhlberg. In articles in Nature Protocols and Nucleic Acids Research, he and his colleagues talk about how the ultra-sensitive mutation analyses find individual tumor cell molecules among 10,000 healthy molecules. The method is now also being implemented as a generic platform at Sahlgrenska University Hospital by the Wallenberg Center for Molecular and Translational Medicine at University of Gothenburg, in close collaboration with the hospital, and with the backing of Astra Zeneca and Region Västra Götaland. "The method has major potential and should soon be ready for patients. However, first the application need to be tested on patient material in clinical studies, there really is no way around that," says Göran Landberg, professor and director of the Wallenberg Center, who has the task of bringing research and clinical work together. "We work together closely both at the hospital and the university, and with Astra Zeneca. These efforts are completely in line with our ambitions," says Göran Landberg. Screening of at-risk groups for certain types of cancer, leading to earlier diagnosis, is being described as an area with major potential, both with regard to saving lives and saving money within healthcare. No tissue samples are needed for the method, and the tumor does not even need to be located. It can also be used in the calibration of chemotherapy treatments, and help to avoid problematic under- and overdosage. It can also be used to discover whether a patient is becoming resistant to a certain cancer drug, according to Anders Ståhlberg. "There is a great need for something like this in this area. After all, targeted treatments work well for some patients at the moment, but not others. We hope to be able to find out how well a treatment is going, detect relapses at an early stage and improve our options with regard to changing treatments," he says.


News Article | May 22, 2017
Site: phys.org

"We can screen at-risk patient groups, and we also plan to spot the cancer patients who are relapsing so that we can adapt their treatment," says Anders Ståhlberg, docent in molecular medicine and corresponding author for two articles about the method. The technique was created based on the fact that people with cancer also have DNA from tumor cells circulating in the blood, molecules that can be discovered in a regular blood sample long before the tumor is visible via imaging such as tomography, MRI, X-ray and ultrasound. The researchers have now increased the sensitivity of detecting tumor DNA in blood thousand-fold by eliminating the background noise from the measurements using "DNA barcoding". "One of the benefits of the technique is that it makes use of available instrumentation, which means it can be applied in most labs. We are not first in the world to show that barcoding concept works, but in our case we have developed a fast and flexible method that is simple, flexible and cost-effective to use," says Anders Ståhlberg. In articles in Nature Protocols and Nucleic Acids Research, he and his colleagues talk about how the ultra-sensitive mutation analyses find individual tumor cell molecules among 10,000 healthy molecules. The method is now also being implemented as a generic platform at Sahlgrenska University Hospital by the Wallenberg Center for Molecular and Translational Medicine at University of Gothenburg, in close collaboration with the hospital, and with the backing of Astra Zeneca and Region Västra Götaland. "The method has major potential and should soon be ready for patients. However, first the application need to be tested on patient material in clinical studies, there really is no way around that," says Göran Landberg, professor and director of the Wallenberg Center, who has the task of bringing research and clinical work together. "We work together closely both at the hospital and the university, and with Astra Zeneca. These efforts are completely in line with our ambitions," says Göran Landberg. Screening of at-risk groups for certain types of cancer, leading to earlier diagnosis, is being described as an area with major potential, both with regard to saving lives and saving money within healthcare. No tissue samples are needed for the method, and the tumor does not even need to be located. It can also be used in the calibration of chemotherapy treatments, and help to avoid problematic under- and overdosage. It can also be used to discover whether a patient is becoming resistant to a certain cancer drug, according to Anders Ståhlberg. "There is a great need for something like this in this area. After all, targeted treatments work well for some patients at the moment, but not others. We hope to be able to find out how well a treatment is going, detect relapses at an early stage and improve our options with regard to changing treatments," he says. Explore further: Researchers use math to develop personalized chemo treatments


News Article | May 8, 2017
Site: www.eurekalert.org

A stringently designed web form with questions about foot ulcers, deformities and neuropathy will soon be brought into use to better protect the feet of people with diabetes. The tool is a result of research conducted at Sahlgrenska Academy. "One of the reasons why patients in the risk zone are not detected in time is that there is no standardised procedure of foot examination which means risk assessment is subjective," says Doctor of Philosophy Ulla Hellstrand Tang, a certified prosthetist and orthotist with long experience in the care of diabetes patients with feet problems. "Foot ulcers are a common cause of amputation for people with diabetes. The National Board of Health and Welfare recommends diabetics to have their feet checked but routines are inadequate and there are large regional differences," says Ulla Hellstrand Tang. In her research, Hellstrand Tang has now developed a simple, standardised e-health tool for the risk assessment of feet. Clear descriptions and pictures guide the person through the 22 self-examination steps so there can be no uncertainty about the patient's status. The patient is asked questions about, for example, mobility, foot ulcers, numbness and degree of perspiration. Reduced foot perspiration may indicate a nerve injury. Likewise, the presence of a bunion (hallux valgus), hammer toe or other deformity is examined, and so on. All the question variables have been scientifically tested so that a certain condition is always given the same classification and treatment recommendation. In the autumn, Sahlgrenska University Hospital in Gothenburg will start to use the D-Foot tool and it is hoped that other clinics will do the same. "I am very pleased that the tool is being taken into use so soon and can thereby help patients," says Ulla Hellstrand Tang. She has also investigated which aids best protect patients' feet from unnecessarily high pressure. In a two-year study, about a hundred patients tested both prefabricated and individually designed insoles. Pressure was measured regularly at seven different measuring points under the feet. The heels were subjected to the strongest pressure. "It was shown that a personally designed insole gives a closer fit around the heel cushion, provides support to a larger area, and reduces pressure significantly more than a traditional, prefabricated insole does," says Ulla Hellstrand Tang. "However, we could also see that combinations of good shoes and prefabricated insoles created good support and acceptable pressure for some people. A patient whose feet are in relatively good shape can begin by using a cheaper and simpler insole. The advantage of this is that the patient's treatment is completed after just one visit and no return appointment after two-three weeks is necessary," she says.


Ben-Menachem E.,Sahlgrenska University Hospital
Epilepsia | Year: 2014

The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review. © 2014 International League Against Epilepsy.


Tremaroli V.,Sahlgrenska University Hospital | Tremaroli V.,Gothenburg University | Backhed F.,Sahlgrenska University Hospital | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS
Nature | Year: 2012

The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease. © 2012 Macmillan Publishers Limited. All rights reserved.


Andersson J.,Sahlgrenska University Hospital
The British journal of surgery | Year: 2013

Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12 months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial. The setting was a multicentre randomized trial (COLOR II) comparing laparoscopic and open surgery for rectal cancer. Involvement in the HRQL study of COLOR II was optional. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and EuroQol - 5D (EQ-5D™) before surgery, and 4 weeks, 6, 12 and 24 months after operation. Analysis was done according to the manual for each instrument. Of 617 patients in hospitals participating in the HRQL study of COLOR II, 385 were included. The HRQL deteriorated to moderate/severe degrees after surgery, gradually returning to preoperative values over time. Changes in EORTC QLQ-C30 and QLQ-CR38, and EQ-5D™ were not significantly different between the groups regarding global health score or any of the dimensions or symptoms at 4 weeks, 6 or 12 months after surgery. In contrast to previous studies in patients with colonic cancer, HRQL after rectal cancer surgery was not affected by surgical approach. Registration number: NCT0029779 (http://www.clinicaltrials.gov). © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.


The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911.


Hagman A.,Sahlgrenska University Hospital
Human reproduction (Oxford, England) | Year: 2013

Do women with Turner karyotype have increased mortality and morbidity in the years after childbirth? No mortality occurred during pregnancy and follow-up in women with Turner karyotype, but a higher rate of circulatory and endocrine diseases and a high risk of aortic aneurysm were confirmed. Pregnancies in women with Turner karyotype are high-risk pregnancies with an increased risk of maternal mortality from aortic dissection and morbidity from hypertensive disorders. A retrospective Swedish population-based registry study of 124 women with Turner karyotype born between 1957 and 1987 and who gave birth between 1973 and 2010. Women with Turner karyotype without childbirth (n = 378) were selected as controls. A second control group consisted of women from the Swedish Medical Birth Register (MBR) (n = 1230) matched for maternal age, number of children and year of birth of the first child. Women with Turner karyotype were identified in the Swedish Genetic Turner Register. Data were obtained by using the unique personal identification number with cross linkage to the Swedish MBR, the Cause of Death Register, the National Patient Register and the Swedish Cancer Register. Hazard ratio (HR) with 95% confidence interval (CI) was used in the analysis of morbidity. No mortality occurred in women with Turner karyotype and childbirth. Diseases of the circulatory system occurred more often in women with Turner syndrome under the age of 40 years compared with the MBR control group (HR 4.59; 95% CI 2.75-7.66) but was similar at or above the age of 40 years. Morbidity from circulatory diseases was increased before pregnancy (HR 3.83; 95% CI 1.02-14.43) and during pregnancy or within 1 year after (HR 5.78; 95% CI 1.94-17.24), but was similar after 1 or more years after delivery (HR 1.91; 95% CI 0.74-4.96). Aortic aneurysm occurred in 11/502 (2.2%) women with Turner karyotype and in three women (2.4%) during pregnancy. The long-term follow-up showed that aortic dissection was a common cause of death in young women with Turner karyotype without childbirth. A thorough cardiac evaluation before pregnancy in women with Turner karyotype is of utmost importance. Although this was a population-based registry study performed over a period of more than 20 years, a much longer follow-up and larger series are needed to assess rare events. The study also lacks information on phenotype and mode of conception in women with Turner karyotype. Women who gave birth probably represent a selection of healthier women with Turner karyotype. The high risk of aortic aneurysm in young women with Turner karyotype is in agreement with the literature.


Sondergaard S.,Sahlgrenska University Hospital
Critical Care | Year: 2013

Hemodynamic management of critically ill patients in the ICU or high-risk patients in the operating room has paradoxically shown progress in terms of outcome after the systematic application of volume responsiveness/flow optimization based on pulse pressure variation and/or stroke volume variation during controlled, positive-pressure ventilation in patients without spontaneous respiratory efforts. This assessment of circulatory optimization should ideally be based on an exhaustive, predictive and coherent physiological understanding of the cardiovascular system model. This paper sketches the extremely complex physiological background of the concept of volume responsiveness, concluding that it is not a reliable means of guiding hemodynamic optimization because it is based on a nonexhaustive, nonpredictive and incoherent physiological model. © 2013 BioMed Central Ltd.


Wallinder A.,Sahlgrenska University Hospital
The Journal of thoracic and cardiovascular surgery | Year: 2012

Ex vivo lung perfusion has the potential to increase the number of patients treated with lung transplantation. Our initial clinical experience with ex vivo lung perfusion is reviewed as well as early clinical outcome in patients transplanted with reconditioned lungs. Six pairs of donor lungs deemed unsuitable for transplantation underwent ex vivo lung perfusion with Steen solution mixed with red blood cells to a hematocrit of 10% to 15%. After reconditioning, lung function was evaluated and acceptable lungs were transplanted. Technical experience with ex vivo lung perfusion as well as clinical outcome for patients transplanted with ex vivo lung perfusion-treated lungs were evaluated. Donor lungs initially rejected either as a result of an inferior partial pressure of arterial oxygen/ fraction of inspired oxygen (n = 5; mean, 20.5 kPa; range, 9.1-29.9 kPa) or infiltrate on chest radiograph (n = 1) improved their oxygenation capacity to a mean partial pressure of arterial oxygen/fraction of inspired oxygen of 57 ± 10 kPa during the ex vivo lung perfusion (mean improvement, 33.6 kPa; range, 21-51 kPa; P < .01). During evaluation, hemodynamic (flow, vascular resistance, pressure) and respiratory (peak airway pressure, compliance) parameters were stable. Two single lungs were not used for lung transplantation because of subpleural hematoma or edema. Six recipients from the regular waiting list underwent single (n = 2) or double (n = 4) lung transplantation. One patient had primary graft dysfunction grade 2 at 72 hours. Median time to extubation was 7 hours. All patients survived 30 days and were discharged in good condition from the hospital. The use of ex vivo lung perfusion seems safe and indicates that some lungs otherwise refused for lung transplantation can be recovered and transplanted with acceptable short-term results. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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