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  • 1. Aarseth, Espen
    et al.
    Bean, Anthony M.
    Boonen, Huub
    Carras, Michelle Colder
    Coulson, Mark
    Das, Dimitri
    Deleuze, Jory
    Dunkels, Elza
    Umeå University, Faculty of Social Sciences, Department of applied educational science.
    Edman, Johan
    Ferguson, Christopher J.
    Haagsma, Maria C.
    Bergmark, Karin Helmersson
    Hussain, Zaheer
    Jansz, Jeroen
    Kardefelt-Winther, Daniel
    Kutner, Lawrence
    Markey, Patrick
    Nielsen, Rune Kristian Lundedal
    Prause, Nicole
    Przybylski, Andrew
    Quandt, Thorsten
    Schimmenti, Adriano
    Starcevic, Vladan
    Stutman, Gabrielle
    Van Looy, Jan
    Van Rooij, Antonius J.
    Scholars' open debate paper on the World Health Organization ICD-11 Gaming Disorder proposal2017In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, no 3, p. 267-270Article in journal (Other academic)
    Abstract [en]

    Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world.

  • 2.
    Aasa, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Norrlandsklinikens hälsocentral, Umeå, Sweden.
    Berglund, Lars
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Michaelson, Peter
    Luleå Tekniska Universitet, Institutionen för hälsovetenskap, Avdelningen för hälsa och rehabilitering, Fysioterapi.
    Aasa, Ulrika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Individualized low-load motor control exercises and education versus a high-load lifting exercise and education to improve activity, pain intensity, and physical performance in patients with low back pain: a randomized controlled trial2015In: Journal of Orthopaedic and Sports Physical Therapy, ISSN 0190-6011, E-ISSN 1938-1344, Vol. 45, no 2, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Study Design Randomized controlled trial. Background Low back pain is a common disorder. Patients with low back pain frequently have aberrant and pain-provocative movement patterns that often are addressed with motor control exercises. Objective To compare the effects of low-load motor control (LMC) exercise and those of a high-load lifting (HLL) exercise. Methods Seventy participants with recurrent low back pain, who were diagnosed with nociceptive mechanical pain as their dominating pain pattern, were randomized to either LMC or HLL exercise treatments. Participants were offered 12 treatment sessions over an 8-week period. All participants were also provided with education regarding pain mechanisms. Methods Participants were assessed prior to and following treatment. The primary outcome measures were activity (the Patient-Specific Functional Scale) and average pain intensity over the last 7 days (visual analog scale). The secondary outcome measure was a physical performance test battery that included 1 strength, 3 endurance, and 7 movement control tests for the lumbopelvic region. Results Both interventions resulted in significant within-group improvements in pain intensity, strength, and endurance. The LMC group showed significantly greater improvement on the Patient-Specific Functional Scale (4.2 points) compared with the HLL group (2.5 points) (P<.001). There were no significant between-group differences in pain intensity (P = .505), strength, and 1 of the 3 endurance tests. However, the LMC group showed an increase (from 2.9 to 5.9) on the movement control test subscale, whereas the HLL group showed no change (from 3.9 to 3.1) (P<.001). Conclusion An LMC intervention may result in superior outcomes in activity, movement control, and muscle endurance compared to an HLL intervention, but not in pain intensity, strength, or endurance.

  • 3.
    Aasa, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lundell, Sara
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Aasa, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Norrlandskliniken, Umeå, Sweden.
    Westerståhl, Maria
    Institutionen för laboratoriemedicin, Karolinska institutet.
    Physical Activity Might Be of Greater Importance for Good Spinal Control Than If You Have Had Pain or Not: A Longitudinal Study2015In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 40, no 24, p. 1926-1933Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Longitudinal design. A cohort followed in 3 waves of data collection.

    OBJECTIVE: The aim of the study was to describe the relationships between the performance of 2 tests of spinal control at the age of 52 years and low back pain, physical activity level, and fitness earlier in life, as well as to describe the cross-sectional relationships between these measures.

    SUMMARY OF BACKGROUND DATA: Altered spinal control has been linked to pain; however, other stimuli may also lead to inability to control the movements of the spine.

    METHODS: Participants answered questions about physical activity and low back pain, and performed physical fitness tests at the age of 16, 34, and 52 years. The fitness test battery included tests of endurance in the back and abdominal muscles, a submaximal bicycle ergometer test to estimate maximal oxygen uptake, and measurements of hip flexion, thoracic spine flexibility, and anthropometrics. Two tests were aggregated to a physical fitness index. At the age of 52, also 2 tests of spinal control, the standing Waiter's bow (WB) and the supine double leg lower (LL) were performed.

    RESULTS: Logistic regression analyses showed that higher back muscle endurance at the age of 34 years could positively predict WB performance at 52 years and higher physical fitness at the age of 34 could positively predict LL performance at 52 years. Regarding cross-sectional relationships, an inability to perform the WB correctly was associated with lower physical fitness, flexibility and physical activity, and larger waist circumference. An inability to correctly perform the LL was associated with lower physical fitness. One-year prevalence of pain was not significantly associated with WB or LL test performance.

    CONCLUSION: An active life resulting in higher physical fitness is related to better spinal control in middle-aged men and women. This further strengthens the importance of physical activity throughout the life span.

    LEVEL OF EVIDENCE: 3.

  • 4. Aazh, Hashir
    et al.
    Knipper, Marlies
    Danesh, Ali A.
    Cavanna, Andrea E.
    Andersson, Linus
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Paulin, Johan
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Schecklmann, Martin
    Heinonen-Guzejev, Marja
    Moore, Brian C. J.
    Insights from the Third International Conference on Hyperacusis: Causes, Evaluation, Diagnosis, and Treatment2018In: Noise & Health, ISSN 1463-1741, E-ISSN 1998-4030, Vol. 20, no 95, p. 162-170Article in journal (Refereed)
    Abstract [en]

    Background: Hyperacusis is intolerance of certain everyday sounds that causes significant distress and impairment in social, occupational, recreational, and other day-to-day activities. Objective: The aim of this report is to summarize the key findings and conclusions from the Third International Conference on Hyperacusis. Topics covered: The main topics discussed comprise (1) diagnosis of hyperacusis and audiological evaluations, (2) neurobiological aspect of hyperacusis, (3) misophonia, (4) hyperacusis in autism spectrum disorder, (5) noise sensitivity, (6) hyperacusis-related distress and comorbid psychiatric illness, and (7) audiologist-delivered cognitive behavioral therapy for hyperacusis. Conclusions: Implications for research and clinical practice are summarised.

  • 5. Abbara, Aula
    et al.
    Rawson, Timothy M.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    El-Amin, Wael
    Hatcher, James
    Tajaldin, Bachir
    Dar, Osman
    Dewachi, Omar
    Abu Sitta, Ghassan
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sparrow, Annie
    Antimicrobial resistance in the context of the Syrian conflict: Drivers before and after the onset of conflict and key recommendations2018In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 73, p. 1-6Article, review/survey (Refereed)
    Abstract [en]

    Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress. 

  • 6. Abbas, S
    et al.
    Linseisen, J
    Rohrmann, S
    Beulens, JWJ
    Buijsse, B
    Amiano, P
    Ardanaz, E
    Balkau, B
    Boeing, H
    Clavel-Chapelon, F
    Fagherazzi, G
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gavrila, D
    Grioni, S
    Kaaks, R
    Key, TJ
    Khaw, KT
    Kuehn, T
    Mattiello, A
    Molina-Montes, E
    Nilsson, PM
    Overvad, K
    Quiros, JR
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, C
    Saieva, C
    Slimani, N
    Sluijs, I
    Spijkerman, AMW
    Tjonneland, A
    Tumino, R
    van der A, DL
    Zamora-Ros, R
    Sharp, SJ
    Langenberg, C
    Forouhi, NG
    Riboli, E
    Wareham, NJ
    Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study2014In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, no 2, p. 196-202Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.

    SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires.

    RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D.

    CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

  • 7. Abbas, Sascha
    et al.
    Linseisen, Jakob
    Rohrmann, Sabine
    Chang-Claude, Jenny
    Peeters, Petra H
    Engel, Pierre
    Brustad, Magritt
    Lund, Eiliv
    Skeie, Guri
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Kaaks, Rudolf
    Boeing, Heiner
    Buijsse, Brian
    Adarakis, George
    Ouranos, Vassilis
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Buckland, Genevieve
    Suárez, Marcial Vicente Argüelles
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Amiano, Pilar
    Manjer, Jonas
    Wirfält, Elisabet
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bueno-de-Mesquita, H B
    van Duijnhoven, Fränzel J B
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Fedirko, Veronika
    Romieu, Isabelle
    Gallo, Valentina
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Dietary intake of vitamin D and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition2013In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 65, no 2, p. 178-187Article in journal (Refereed)
    Abstract [en]

    Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.

  • 8.
    Abedpour Dehkordi, Adel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nayeri, H.
    Naderi, G. A.
    Dinani, N. Jafari
    Boshtam, M.
    Interleukin-6 reduces paraoxonase-1 activity in a dose-dependent manner: evidence for a potential novel lipoprotein-based modulatory mechanism2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 252, p. E113-E114Article in journal (Other academic)
    Abstract [en]

    Objectives: The anti-oxidant/anti-inflammatory nature of HDL is mainly associated with paraoxonase-1 (PON1). Previous studies have revealed an inverse correlation between Interleukin-6 (IL-6) and PON1 expression. The current study investigates the effect of IL-6 on serum PON1 activity in vitro, given the potential structural capability of PON1 to host multiple ligands. Methods: PON1 activity was measured spectrophotometrically (234 nm) using paraoxon substrate in the presence of concentrations of IL-6 than control samples. A sequence alignment using the FASTA sequence was manually conducted to identify possible homologies between PON1 and the IL-6-binding protein. Statistical analysis was conducted using GraphPad Prism v5.0. Results: PON1 enzyme activity decreased by 15%, 26% (P<0.05) and 55% (P<0.001) in the presence of 4, 10 and 20 pg/ml of IL-6, respectively. in comparison with the controls. Student t. test was used as statistical method (p<0.05: statistically significant). There are potential homologies between PON1 active sites and know IL-6-binding residues. Conclusions: This study shows that IL-6 directly reduce the PON1 activity in a dose-dependent manner. This observation supports some studies indicating inverse correlation between PON1 and IL-6. However, as opposed to the gene-mediated approach, this study suggest that IL-6 may act directly through specific binding to PON1 (biochemical modulation). X ray crystallography can further scrutinize the present finding.

  • 9. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e64899-Article in journal (Refereed)
    Abstract [en]

    Background: Genetic studies are challenging in many complex diseases, particularly those with limited diagnostic certainty, low prevalence or of old age. The result is that genes may be reported as disease-causing with varying levels of evidence, and in some cases, the data may be so limited as to be indistinguishable from chance findings. When there are large numbers of such genes, an objective method for ranking the evidence is useful. Using the neurodegenerative and complex disease amyotrophic lateral sclerosis (ALS) as a model, and the disease-specific database ALSoD, the objective is to develop a method using publicly available data to generate a credibility score for putative disease-causing genes.

    Methods: Genes with at least one publication suggesting involvement in adult onset familial ALS were collated following an exhaustive literature search. SQL was used to generate a score by extracting information from the publications and combined with a pathogenicity analysis using bioinformatics tools. The resulting score allowed us to rank genes in order of credibility. To validate the method, we compared the objective ranking with a rank generated by ALS genetics experts. Spearman's Rho was used to compare rankings generated by the different methods.

    Results: The automated method ranked ALS genes in the following order: SOD1, TARDBP, FUS, ANG, SPG11, NEFH, OPTN, ALS2, SETX, FIG4, VAPB, DCTN1, TAF15, VCP, DAO. This compared very well to the ranking of ALS genetics experts, with Spearman's Rho of 0.69 (P = 0.009).

    Conclusion: We have presented an automated method for scoring the level of evidence for a gene being disease-causing. In developing the method we have used the model disease ALS, but it could equally be applied to any disease in which there is genotypic uncertainty.

  • 10. Abosch, Aviva
    et al.
    Timmermann, Lars
    Bartley, Sylvia
    Rietkerk, Hans Guido
    Whiting, Donald
    Connolly, Patrick J.
    Lanctin, David
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An International Survey of Deep Brain Stimulation Procedural Steps2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, p. 1-11Article, review/survey (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders.

    Objective: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed.

    Methods: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters.

    Results: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers.

    Conclusions: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

  • 11. Abrahamsson, Niclas
    et al.
    Borjesson, Joey Lau
    Sundbom, Magnus
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, F. Anders
    Eriksson, Jan W.
    Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 12.
    Abrahamsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Methodological aspects on microdialysis sampling and measurements2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background:     The microdialysis (MD) technique is widely spread and used both experi­mentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser.  Data evaluating the performance of the CMA 600 analysis system and associated sample han­dling are sparse. The aim of this work was to identify sources of variability related to han­dling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the micro­dialysis probes both within an organ and on the surface of an organ.

     Material and Methods:  Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to exam­ine the true concen­tration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in associa­tion with induced liver ischemia. All animal studies were approved by the Animal Experi­mental Ethics Committee at Umeå University Sweden.

    Results:  In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The sur­face probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver paren­chyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interven­tions.

    Conclusion:  The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentra­tions sampled from the myocardium and liver parenchyma, respectively.

  • 13.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Outcome of microdialysis sampling on liver surface and parenchyma2016In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 200, no 2, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.

    Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.

    Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.

    Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.

  • 14.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    An assessment of calibration and performance of the microdialysis system2005In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 39, no 3-4, p. 730-734Article in journal (Refereed)
    Abstract [en]

    To improve the reliability of microdialysis measurements of tissue concentrations of metabolic substances, this study was designed to test both the performance and the internal validity of the microdialysis methods in the hands of our research group. The stability of the CMA 600 analyser was tested with a known glucose solution in 72 standard microvials and in 48 plastic vials. To evaluate if variation in sampling time makes any difference in sample concentration (recovery), sampling times of 10, 20 and 30 min were compared in vitro with a constant flow rate of 1 microl/min. For testing of sampling times at different flow rates, an in vitro study was performed in which a constant sample volume of 10 microl was obtained. With the no net flux method, the actual concentration of glucose and urea in subcutaneous tissue was measured. The CMA 600 glucose analysis function was accurate and stable with a coefficient of variability (CV) of 0.2-0.55%. There was no difference in recovery for the CMA 60 catheter for glucose when sampling times were varied. Higher flow rates resulted in decreased recovery. Subcutaneous tissue concentrations of glucose and urea were 4.4 mmol/l and 4.1 mmol/l, respectively. To conclude, this work describes an internal validation of our use of the microdialysis system by calibration of vials and catheters. Internal validation is necessary in order to be certain of adequate sampling times, flow rates and sampling volumes. With this in mind, the microdialysis technique is useful and appropriate for in vivo studies on tissue metabolism.

  • 15.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Kirurgi, Skåne Universitets sjukhus, Lund.
    Comparison between outcome of  surface and intraparenchymatous sampling using microdialysis in an experimental liver ischemia modelManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction. We recently have shown that samples from MD probes placed on the surface of the heart reflect metabolic events in the myocardium. This new interesting observation challenges us to consider whether surface application of MD applies to other parenchymatous organs and their surfaces.

    Material and methods.  In thirteen anesthetized pigs transient liver ischemia was achieved by occlusion of arterial and venous inflow to the liver. Two probes on liver surface, and two in parenchyma were perfused with a flow rate of 1 µL/min (n=13). An identical set up was used for probes with a flow rate of 2 µL/min (n=9). Samples were collected for every 15 minute period during 60 minutes of baseline, 45 minutes of ischemia and 60 minutes of reperfusion. Lactate, glucose, pyruvate and glycerol were analysed in MD samples. We focused on relative changes in the present paper.

    Results. There was a strong agreement in relative lactate and glucose levels between probes placed on liver surface and parenchyma. No significant differences in relative changes of lactate and glucose levels were seen between samples from surface probes and probes in liver parenchyma during equilibration, baseline, ischemia or reperfusion with a flow rate of 1 µL/min.

    Conclusion. MD sampling applied on the liver surface is a new application area for the MD technique, and may be used to monitor liver metabolism both during physiological and pathophysiological conditions.

  • 16.
    Abrahamsson, Pernilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Åberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Blind, Per-Jonas
    Surface microdialysis sampling: a new approach described in a liver ischaemia model2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 2, p. 99-105Article in journal (Refereed)
    Abstract [en]

    We recently have shown that samples from microdialysis (MD) probes placed on the surface of the heart reflect metabolic events in the myocardium. This new interesting observation challenges us to consider whether surface application of MD applies to other parenchymatous organs and their surfaces. In 13 anesthetized pigs, transient liver ischaemia was achieved by occlusion of arterial and venous inflow to the liver. Two probes on liver surface and two in parenchyma were perfused with a flow rate of 1 mu l per min (n = 13). An identical set-up was used for probes with a flow rate of 2 mu l per min (n = 9). Samples were collected for every 15-min period during 60 min of baseline, 45 min of ischaemia and 60 min of reperfusion. Lactate, glucose, pyruvate and glycerol were analysed in MD samples. We focused on relative changes in the present study. There was a strong agreement in relative lactate and glucose levels between probes placed on liver surface and those on parenchyma. No significant differences in relative changes in lactate and glucose levels were seen between samples from surface probes and probes in liver parenchyma during equilibration, baseline, ischaemia or reperfusion with a flow rate of 1 mu l per min. MD sampling applied on the liver surface is a new application area for the MD technique and may be used to monitor liver metabolism during both physiological and pathophysiological conditions.

  • 17.
    Abramsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Adherence to Bisphosphonates among People Admitted to an Orthopaedic and Geriatric Ward at a University Hospital in Sweden2018In: Pharmacy, ISSN 2226-4787, E-ISSN 1913-4711, Vol. 6, no 1, article id 20Article in journal (Refereed)
    Abstract [en]

    Oral bisphosphonates are the first choice of therapy to reduce the risk of osteoporotic fractures. These medications have generally poor oral bioavailability, which may further be reduced by concomitant intake of certain foods and drugs; therefore, it is vital to follow specific instructions. The aim with this study was to assess general adherence to oral bisphosphonates and adherence to specific administration instructions among people admitted to two wards at Umeå University hospital in Sweden. This interview study focuses on elderly patients living at home and prescribed oral bisphosphonates. Invited were 27 patients admitted to an orthopaedic ward and a geriatric ward during the period 28 March 2017 and 5 December 2017. In total, 21 patients were interviewed regarding their adherence to oral bisphosphonates. Out of 21 patients, 13 (62%) were considered non-adherent. The most common reason was calcium intake less than 2 h after oral administration of bisphosphonate (54%). The number of regularly prescribed drugs was significantly higher among patients rated non-adherent to bisphosphonates compared to those rated adherent (p = 0.004). Adherence to bisphosphonates administration instruction among elderly people living at home was limited. More research is needed to confirm these results and to investigate the reasons for non-adherence and how adherence to bisphosphonates can be improved.

  • 18. Abul-Kasim, Kasim
    et al.
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Björkman, Anders
    Dahlin, Lars B
    Advanced radiological work-up as an adjunct to decision in early reconstructive surgery in brachial plexus injuries2010In: Journal of Brachial Plexus and Peripheral Nerve Injury, ISSN 1749-7221, E-ISSN 1749-7221, Vol. 5, p. 14-Article in journal (Refereed)
    Abstract [en]

    Background

    As neurophysiologic tests may not reveal the extent of brachial plexus injury at the early stage, the role of early radiological work-up has become increasingly important. The aim of the study was to evaluate the concordance between the radiological and clinical findings with the intraoperative findings in adult patients with brachial plexus injuries.

    Methods

    Seven consecutive male patients (median age 33; range 15-61) with brachial plexus injuries, caused by motor cycle accidents in 5/7 patients, who underwent extensive radiological work-up with magnetic resonance imaging (MRI), computed tomography myelography (CT-M) or both were included in this retrospective study. A total of 34 spinal nerve roots were evaluated by neuroradiologists at two different occasions. The degree of agreement between the radiological findings of every individual nerve root and the intraoperative findings was estimated by calculation of kappa coefficient (К-value). Using the operative findings as a gold standard, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the clinical findings and the radiological findings were estimated.

    Results

    The diagnostic accuracy of radiological findings was 88% compared with 65% for the clinical findings. The concordance between the radiological findings and the intraoperative findings was substantial (К = 0.76) compared with only fair (К = 0.34) for the clinical findings. There were two false positive and two false negative radiological findings (sensitivity and PPV of 0.90; specificity and NPV of 0.87).

    Conclusions

    The advanced optimized radiological work-up used showed high reliability and substantial agreement with the intraoperative findings in adult patients with brachial plexus injury.

  • 19. Achouiti, A.
    et al.
    Vogl, T.
    Urban, Constantin
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Hommes, T. J.
    van Zoelen, M. A.
    Florquin, S.
    Roth, J.
    van 't Veer, C.
    de Vos, A. F.
    van der Poll, T.
    Myeloid related protein (mrp) 8/14 contributes to an antibacterial host response against klebsiella (k.) pneumoniae2012In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, no S1, p. 56-56Article in journal (Other academic)
  • 20. Acosta, Stefan
    et al.
    Block, Tomas
    Björnsson, Steinarr
    Resch, Timothy
    Björck, Martin
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Diagnostic pitfalls at admission in patients with acute superior mesenteric artery occlusion2012In: Journal of Emergency Medicine, ISSN 0736-4679, E-ISSN 1090-1280, Vol. 42, no 6, p. 635-641Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acute superior mesenteric artery (SMA) occlusion leads to acute intestinal ischemia and is associated with high mortality. Early diagnosis is often missed, and confounding factors leading to diagnostic delays need to be highlighted. OBJECTIVES: To identify potential diagnostic laboratory pitfalls at admission in patients with acute SMA occlusion. METHODS: Fifty-five patients with acute SMA occlusion were identified from the in-hospital register during a 4-year period, 2005-2009. RESULTS: The median age was 76 years; 78% were women. The occlusion was embolic in 53% and thrombotic in 47% of patients. At admission, troponin I was above the clinical decision level (> 0.06 μg/L) for acute ischemic myocardial injury in 9/19 (47%) patients with embolic occlusion. Elevated pancreas amylase and normal plasma lactate were found in 12/45 and 13/27, respectively. A troponin I (TnI) above the clinical decision level was associated with a high frequency of referrals from the general surgeon to a specialist in internal medicine (p = 0.011) or a cardiologist (p = 0.024). The diagnosis was established after computed tomography angiography in 98% of the patients. The overall in-hospital mortality rate was 33%. Attempting intestinal revascularization (n = 43; p < 0.001), with a 95% frequency rate of completion control of the vascular procedure, was associated with a higher survival rate, whereas referral to the cardiologist was associated with a higher mortality rate (p = 0.018). CONCLUSION: Elevated TnI was common in acute SMA occlusion, and referral to the cardiologist was found to be associated with adverse outcome. Elevated pancreas amylase and normal plasma lactate values are also potential pitfalls at admission in patients with acute SMA occlusion.

  • 21. Acosta, Stefan
    et al.
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Current status on plasma biomarkers for acute mesenteric ischemia2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 4, p. 355-361Article in journal (Refereed)
    Abstract [en]

    Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: -dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen.

  • 22.
    Adamo, Hanibal
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahl Scherdin, Tove
    Egevad, Lars
    Granfors, Torvald
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.

    In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome. 

  • 23.
    Adamo, Hanibal Hani
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    TINT Tumor Indicating Normal Tissue: new field of diagnostic biomarkers for prostate cancer2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Prostate cancer is the most common cancer in Sweden. Due its highly variable behavior, multifocal nature, and insufficient diagnostic methods, prostate cancer is difficult to diagnose and prognosticate. Some patients have an aggressive lethal disease, but the majority of prostate cancer patients have slow-growing, non-lethal disease with long expected survival without treatment. Current diagnostic methods―serum levels of prostate-specific antigen (PSA) and histological grading of biopsied prostate tissue―often do not give the information required to be able to safely differentiate indolent tumors from potentially lethal ones. Many prostate cancers are difficult to detect by imaging, so tissue biopsy cannot be safely guided towards the tumor, and particularly not towards the most aggressive forms. To overcome this problem, multiple needle biopsies are taken from the organ, but biopsies are small and they sample less than 1% of the whole prostate. In this thesis, we explore the non-malignant prostate tissue adjacent to tumors, which is always sampled in biopsies, and we study adaptive changes in this tissue, which may provide new diagnostic and prognostic markers for prostate cancer. We have therefore proposed that this type of tissue should be termed TINT (Tumor Instructed/indicating Normal Tissue).

     Methods: In our studies, we used orthotopic rat prostate cancer models with tumors of different aggressiveness. We also used clinical materials from patients diagnosed with prostate cancer at transurethral resection (1975‒1990); the majority of these men were followed with watchful waiting. Analyses were performed with whole-genome expression array, quantitative real-time PCR, immunohistochemistry, and western blotting.

     Results: Using the animal model, we found that the presence of a tumor induces changes in gene expression in the surrounding tumor-bearing organ (TINT). The gene signature of TINT was linked to processes such as extracellular matrix organization, immune responses, and inflammation. We also showed that some of these adaptive TINT changes appear to be related to the aggressiveness and metastatic potential of the growing tumor, such as increases in macrophages, in mast cells, in vascular densities, and in vascular cell-proliferation. Some of these findings were confirmed by our observations in patient samples. We found that high staining of the extracellular matrix component hyaluronan in the stroma of the non-malignant prostate tissue was prognostic for short cancer-specific survival. We also found that an elevated proportion of C/EBP-beta positive epithelial cells in non-malignant (TINT) prostate tissue was associated with a good prognosis.

     Conclusions: Using animal experiments and patient samples, we showed that the presence of prostate cancer induces changes in the tumor-bearing organ, alterations associated with tumor aggressiveness, and that grading of these changes in TINT can be used to predict outcome in prostate cancer patients. 

  • 24.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergström, Sofia Halin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0130076Article in journal (Refereed)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.

  • 25.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Strömvall, Kerstin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0141601Article in journal (Refereed)
    Abstract [en]

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.

  • 26.
    Adamo, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sandblom, Gabriel
    Brännström, Fredrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Prevalence and recurrence rate of perianal abscess -a population-based study, Sweden 1997-20092016In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 31, no 3, p. 669-673Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The aim of this study was to assess the impact of diabetes mellitus, Crohn's disease, HIV/aids, and obesity on the prevalence and readmission rate of perianal abscess.

    METHODS: The study cohort was based on the Swedish National Patient Register and included all patients treated for perianal abscess in Sweden 1997-2009. The prevalence and risk for readmission were assessed in association with four comorbidity diagnoses: diabetes mellitus, Crohn's disease, HIV, and/or AIDS and obesity.

    RESULTS: A total of 18,877 patients were admitted during the study period including 11,138 men and 4557 women (2.4:1). Crohn's disease, diabetes, and obesity were associated with a significantly higher prevalence of perianal abscess than an age- and gender-matched background population (p < 0.05). In univariate analysis, neither age nor gender had any significant impact on the risk for readmission. In a multivariate Cox proportional hazard analysis, Crohns disease was the only significant risk factor for readmission of perianal abscess.

    CONCLUSION: Crohn's disease, diabetes, and obesity increase the risk for perianal abscess. Of these, Crohn's and HIV has an impact on readmission. The pathogenesis and the influence of diabetes and obesity need further research if we are to understand why these diseases increase the risk for perianal abscess but not its recurrence.

  • 27. Adams, D.
    et al.
    Coelho, T.
    Conceicao, E.
    Waddington-Cruz, M.
    Schmidt, H.
    Buades, J.
    Campistol, J. M.
    Pouget, J.
    Berk, J. L.
    Polydefkis, M.
    Ziyadeh, N.
    Partisano, A. M.
    Chen, J.
    Gollob, J.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    PHASE 2 OPEN-LABEL EXTENSION (OLE) STUDY OF PATISIRAN, AN INVESTIGATIONAL RNA INTERFERENCE (RNAI) THERAPEUTIC FOR THE TREATMENT OF HEREDITARY ATTR AMYLOIDOSIS WITH POLYNEUROPATHY2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 5, p. A211-A212Article in journal (Other academic)
  • 28. Adams, D.
    et al.
    Coelho, T.
    Conceicao, I.
    Cruz, M. Waddington
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Ziyadeh, N.
    Partisano, A.
    Chen, J.
    Sweetser, M.
    Gollob, J.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Phase 2 open-label extension (OLE) study of patisiran with or without a TTR stabilizer for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 31-32Article in journal (Other academic)
  • 29. Adams, D.
    et al.
    Coelho, T.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Waddington-Cruz, M.
    Schmidt, H.
    Campistol, J.
    Pouget, J.
    Buades, J.
    Falzone, R.
    Harrop, J.
    De Frutos, R.
    Butler, J.
    Cehelsky, J.
    Nochur, S.
    Vaishnaw, A.
    Gollob, J.
    Interim results from phase ii trial of aln-ttr02, a novel RNAi therapeutic for the treatment of familial amyloidotic polyneuropathy2013In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 18, no Supplement 2, p. 1-2Article in journal (Other academic)
  • 30. Adams, D.
    et al.
    Gonzalez-Duarte, A.
    O'Riordan, W. D.
    Yang, C. -C
    Ueda, M.
    Kristen, A. V.
    Tournev, I.
    Schmidt, H. H.
    Coelho, T.
    Berk, J. L.
    Lin, K. -P
    Vita, G.
    Attarian, S.
    Plante-Bordeneuve, V.
    Mezei, M. M.
    Campistol, J. M.
    Buades, J.
    Brannagan, T. H. , I I I
    Kim, B. J.
    Oh, J.
    Parman, Y.
    Sekijima, Y.
    Hawkins, P. N.
    Solomon, S. D.
    Polydefkis, M.
    Dyck, P. J.
    Gandhi, P. J.
    Goyal, S.
    Chen, J.
    Strahs, A. L.
    Nochur, S. V.
    Sweetser, M. T.
    Garg, P. P.
    Vaishnaw, A. K.
    Gollob, J. A.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 1, p. 11-21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

    METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).

    RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.

    CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.

  • 31. Adams, David
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hund, Ernst
    Obici, Laura
    Tournev, Ivailo
    Campistol, Josep M.
    Slama, Michel S.
    Hazenberg, Bouke P.
    Coelho, Teresa
    First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy2016In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 29, p. S14-S26Article in journal (Refereed)
    Abstract [en]

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.

  • 32. Adams, David
    et al.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Schmidt, Hartmut
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Berk, John
    Coelho, Teresa
    Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 11Article in journal (Other academic)
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    Jennings, Vicky
    Ngayu, Nyawira
    Moore, Rachel
    Kong, Victor
    Sampson, Colleen
    Panieri, Eugenio
    Tun, Myint
    Mphatsoe, Albert Mohale
    Carreira, Jo-Anne
    Teasdale, Ella
    Wagener, Mark
    Botes, Stefan
    Du Plessis, Danelo
    Pagnozzi, Janet
    Quezada, Jimy Harold Jara
    Rodicio, Jose Luis
    Minguez, German
    Rodriguez-Uria, Raquel
    Ugalde, Paul
    Lopez-Arevalo, Camilo
    Barneo, Luis
    Gonzales Stuva, Jessica Patricia
    Aguilar-Jimenez, Jose
    Andres Garcia-Marin, Jose
    Ortega-Vazquez, Irene
    Rodriguez, Lorena
    Herrera, Norberto
    Arachchi, Prasad Pitigala
    Jan, Wanigasekara Senanayake Mudiyanselage Kithsiri
    Arachchige, Lalith Asanka Jayasooriya Jayasooriya
    Sivaganesh, Sivasuriya
    Samaraweera, Dulan Irusha
    Thanusan, Vimalakanthan
    Musa, Ahmed Elgaili Khalid
    Balila, Reem Mohammed Hassan
    Mohamed, Mohamed Awad Elkarim Hamad
    Ali, Hussein
    Elabdin, Hagir Zain
    Hassan, Alaa
    Mahdi, Sefeldin
    Ahmed, Hala
    Idris, Sahar Abdoun Ishag
    Elsayed, Makki
    Elsayed, Mohammed
    Mahmoud, Mohamed
    Thorarinsdottir, Hildur
    Utter, Maria
    Sundstrom, Sami Martin
    Wredberg, Cecilia
    Kjellin, Ann
    Nyberg, Johanna
    Frisk, Bjorn
    Ahlqvist, Sandra
    Bjorklund, Ida
    Hjertberg, Maria
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Andersson, Linda
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Royson, Hanna
    Weber, Per
    Schmid, Roger
    Schivo, Debora
    Despotidis, Vasileios
    Breitenstein, Stefan
    Staerkle, Ralph F.
    Schadde, Erik
    Deichsel, Fabian
    Gerosa, Alexandra
    Nocito, Antonio
    Raptis, Dimitri Aristotle
    Mijuskovic, Barbara
    Zuber, Markus
    Eisner, Lukas
    Kruspi, Swantje
    Reinisch, Katharina Beate
    Schoewe, Christin
    Novak, Allan
    Palma, Adrian F.
    Teufelberger, Gerfried
    Balkan, Ali Zeynel Abidin
    Gumar, Mehmet
    Yavuz, Mehmet Ali
    Karabacak, Ufuk
    Lap, Gokhan
    Ozkan, Bahar Busra
    Adams, Ryan
    Morton, Robert
    Henderson, Liam
    Gratton, Ruth
    Clement, Keiran David
    Chang, Kate Yu-Ching
    McNish, David
    McIntosh, Ryan
    Milligan, William
    Skelly, Brendan
    Anderson-Knight, Hannah
    Lawther, Roger
    Onimowo, Jemina
    Shatkar, Veereanna
    Tharmalingam, Shivanee
    Woin, Evelina
    Fautz, Tessa
    Ziff, Oliver
    Dindyal, Shiva
    Arman, Sam
    Talukder, Shagorika
    Gadhvi, Vijay
    Chew, Luen Shaun
    Heath, Jonathan
    Mannu, Gurdeep Singh
    Zachariades, Dimitris-Christos
    Snaith, Ailsa Claire
    Hettiarachchi, Thusitha Sampath
    Nesaratnam, Arjun
    Wheeler, James
    Sykes, Mark
    Behar, Nebil
    Jordan, Harriet
    Arulampalam, Tan
    Shah, Apar
    Brown, Damien
    Blower, Emma
    Sutton, Paul
    Gasteratos, Konstantinos
    Vimalachandran, Dale
    Magee, Cathy
    Mcguigan, Andrew
    Mcaleer, Stephen
    Morgan, Clare
    Braungart, Sarah
    Lafferty, Kirsten
    Labib, Peter
    Tanase, Andrei
    Mangan, Clodagh
    Reza, Lillian
    Woodward, Helen
    Gouldthorpe, Craig
    Turner, Megan
    Wild, Jonathan R. L.
    Malik, Tom Am
    Proctor, Victoria K.
    Hewage, Kalon
    Davies, James
    Dubois, Andre
    Sarwary, Sayed
    Zardab, Ali
    Grant, Alan
    Mcintyre, Robert
    Tewari, Shirish
    Humm, Gemma
    Farinella, Eriberto
    Parthiban, Sunil
    Hall, Nigel J.
    Wright, Naomi J.
    Major, Christina P.
    Xerri, Thelma
    De Bono, Phoebe
    Amin, Jasim
    Farhad, Mustafa
    Camilleri-Brennan, John F.
    Robertson, Andrew G. N.
    Swann, Joanna
    Richards, James
    Jabbar, Aijaz
    Attard, Myranda
    Burns, Hannah
    Macdonald, Euan
    Baldacchino, Matthew
    Skehan, Jennifer
    Camilleri-Brennan, Julian
    Hall, Tom Falconer
    Gimzewska, Madelaine
    Mclachlan, Greta
    Shah, Jamie
    Giles, James
    Hassan, Maleeha
    Beasley, William
    Vlachogiorgos, Apostolos
    Dias, Stephen
    Maharaj, Geta
    McDonald, Rosie
    Cross, Kate
    Rees, Clare M.
    Van Duren, Bernard
    Upchurch, Emma
    Karandikar, Sharad
    Bowley, Doug
    Karim, Ahmed
    Chachulski, Witold
    Richardson, Liam
    Dawnay, Giles
    Thompson, Ben
    Mistry, Ajayesh
    Ghetia, Millika
    Roy, Sudipta
    Al-Obaedi, Ossama
    Das, Kaustuv
    Prabhudesai, Ash
    Cocker, D. M.
    Tan, Jessica Juliana
    Vivekanantham, Sayinthen
    Gillespie, Michael
    Gudlaugsdottir, Katrin
    Pezas, Theodore
    Currow, Chelise
    Kim, Matthew Young-Han
    Salama, Yahya
    Shah, Rohi
    Ibrahem, Ahmad Aboelkassem
    Ebdewi, Hamdi
    Gravante, Gianpiero
    El-Rabaa, Saleem
    Chan, Zoe
    Hassan, Zaffar
    Makinde, Misty
    Hemingway, David
    Dean, Ramzana
    Boddy, Alexander
    Aber, Ahmed
    Patel, Vijay
    Kotecha, Deevia
    Ubhi, Harmony Kaur
    Hosein, Simon-Peter
    Ward, Simon
    Malik, Kamran
    Jennings, Leifa
    Newton, Tom
    Alkhouri, Mirna
    Kang, Min Kyu
    Houlden, Christopher
    Barry, Jonathan
    Wilson, Michael S. J.
    Neo, Yan Ning
    Ibrahim, Ibrahim
    Chan, Emily
    Peck, Fraser S.
    Lim, Pei J.
    North, Alexander S.
    Blundell, Rebecca
    Williamson, Adam
    Fouad, Dina
    Minocha, Ashish
    Mccarthy, Kathryn
    Court, Emma
    Chambers, Alice
    Yee, Jenna
    Tham, Ji Chung
    Beaton, Ceri
    Walsh, Una
    Lockey, Joseph
    Bokhari, Salman
    Howells, Lara
    Griffiths, Megan
    Yallop, Laura
    Singh, Shailinder
    Nasher, Omar
    Jackson, Paul
    Ramzi, Saed
    Zeidan, Shady
    Doughty, Jennifer
    Sinha, Sidhartha
    Davenport, Ross
    Lewis, Jason
    Duffy, Leo
    Mcaleer, Elizabeth
    Williams, Eleanor
    Obute, Rhalumi Daniel
    Glover, Thomas E.
    Clark, David J.
    Boshnaq, Mohamed
    Akhtar, Mansoor
    Capleton, Pascale
    Doughan, Samer
    Rabie, Mohamed
    Mohamed, Ismail
    Samuel, Duncan
    Dickson, Lauren
    Kennedy, Matthew
    Dempster, Eleanor
    Brown, Emma
    Maple, Natalie
    Monaghan, Eimear
    Wolf, Bernhard
    Garland, Alicia
    Lund, Jonathan
    Boereboom, Catherine
    Murphy, Jennifer
    Tierney, Gillian
    Tou, Samson
    Zimmermann, Eleanor Franziska
    Smart, Neil James
    Warwick, Andrea Marie
    Stasinou, Theodora
    Daniels, Ian
    Findlay-Cooper, Kim
    Mitrasinovic, Stefan
    Ray, Swayamjyoti
    Varcada, Massimo
    D'souza, Rovan
    Omara, Sharif
    Boyce, Tamsin
    Whewell, Harriet
    Jones, Elin
    Ma, Jennifer
    Abington, Emily
    Ramcharn, Meera
    Williams, Gethin
    Winstanley, Joseph
    Kennedy, Ewan D.
    Yeung, Emily N. W.
    Fergusson, Stuart J.
    Jones, Catrin
    O'neill, Stephen
    Lim, Shujing Jane
    Liew, Ignatius
    Nair, Hari
    Fairfield, Cameron
    Oh, Julia
    Koh, Samantha
    Wilson, Andrew
    Fairfield, Catherine
    Th'ng, Francesca
    Robertson, Nichola
    Anandkumar, Delran
    Kirupagaran, Ashok
    Jones, Timothy F.
    Torrance, Hew D.
    Fowler, Alexander J.
    Chandrakumar, Charmilie
    Patel, Priyank
    Ashraf, Syed Faaz
    Lakhani, Sonam M.
    Mclean, Aaron Lawson
    Basson, Sonia
    Batt, Jeremy
    Bowman, Catriona
    Stoddart, Michael
    Benons, Natasha
    Barker, Tom
    Summerour, Virginia
    Harper, Edward
    Smith, Caroline
    Hampton, Matthew
    Mckechnie, Doug
    Farah, Ayaan
    Chun, Anita
    Pereira, Bernadette
    Nemeth, Kristof
    Decker, Emily
    Giuliani, Stefano
    Shalaby, Aly
    Szczap, Aleksandra
    Chidambaram, Swathikan
    Chen, Chee Yang
    Kulasabanathan, Kavian
    Chhabra, Srishti
    Kostov, Elisabeth
    Harbord, Philippe
    Barnacle, James
    Palliyil, Madan Mohan
    Zikry, Mina
    Porter, Johnathan
    Raslan, Charef
    Hafiz, Shazia
    Soltani, Niksa
    Baillie, Katie
    Mirza, Ahmad
    Saeed, Haroon
    Galloway, Simon
    Elena, Gia
    Afzal, Mohammad
    Zakir, Mohamed
    Sodde, Peter
    Hand, Charles
    Sriram, Aiesha
    Clark, Tamsyn
    Holton, Patrick
    Livesey, Amy
    Sinha, Yashashwi
    Iqbal, Fahad Mujtaba
    Bharj, Indervir Singh
    Rotundo, Adriana
    Jenvey, Cara
    Slade, Robert
    Golding, David
    Haines, Samuel
    Abdullah, Ali Adel Ne'ma
    Tilston, Thomas W.
    Loughran, Dafydd
    Donoghue, Danielle
    Giacci, Lorenzo
    Sherif, Mohamed Ashur
    Harrison, Peter
    Tang, Alethea
    Elshaer, Mohamed
    Urbonas, Tomas
    Riaz, Amjid
    Chapman, Annie
    Acharya, Parisha
    Shalhoub, Joseph
    Grossart, Cathleen
    McMorran, David
    Mlotshwa, Makhosini
    Hawkins, William
    Loizides, Sofronis
    Thomson, Peter
    Khan, Shahab
    Taylor, Fiona
    Shukla, Jalak
    Howie, Emma Elizabeth
    Macdonald, Linda
    Komolafe, Olusegun
    Mcintyre, Neil
    Cragg, James
    Parker, Jody
    Stewart, Duncan
    Lintin, Luke
    Tracy, Julia
    Farooq, Tahir
    Sion, Melanie
    Weinstein, Michael S.
    Punja, Viren
    Bugaev, Nikolay
    Goodstein, Monica
    Razmdjou, Shadi
    Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries2016In: BMJ Global Health, ISSN 2059-7908, Vol. 1, no 4, article id e000091Article in journal (Refereed)
    Abstract [en]

    Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.

    Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.

    Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.

    Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.

  • 34.
    Adjeiwaah, Mary
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Quality assurance for magnetic resonance imaging (MRI) in radiotherapy2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) utilizes the magnetic properties of tissues to generate image-forming signals. MRI has exquisite soft-tissue contrast and since tumors are mainly soft-tissues, it offers improved delineation of the target volume and nearby organs at risk. The proposed Magnetic Resonance-only Radiotherapy (MR-only RT) work flow allows for the use of MRI as the sole imaging modality in the radiotherapy (RT) treatment planning of cancer. There are, however, issues with geometric distortions inherent with MR image acquisition processes. These distortions result from imperfections in the main magnetic field, nonlinear gradients, as well as field disturbances introduced by the imaged object. In this thesis, we quantified the effect of system related and patient-induced susceptibility geometric distortions on dose distributions for prostate as well as head and neck cancers. Methods to mitigate these distortions were also studied.

    In Study I, mean worst system related residual distortions of 3.19, 2.52 and 2.08 mm at bandwidths (BW) of 122, 244 and 488 Hz/pixel up to a radial distance of 25 cm from a 3T PET/MR scanner was measured with a large field of view (FoV) phantom. Subsequently, we estimated maximum shifts of 5.8, 2.9 and 1.5 mm due to patient-induced susceptibility distortions. VMAT-optimized treatment plans initially performed on distorted CT (dCT) images and recalculated on real CT datasets resulted in a dose difference of less than 0.5%.

     The magnetic susceptibility differences at tissue-metallic,-air and -bone interfaces result in local B0 magnetic field inhomogeneities. The distortion shifts caused by these field inhomogeneities can be reduced by shimming.  Study II aimed to investigate the use of shimming to improve the homogeneity of local  B0 magnetic field which will be beneficial for radiotherapy applications. A shimming simulation based on spherical harmonics modeling was developed. The spinal cord, an organ at risk is surrounded by bone and in close proximity to the lungs may have high susceptibility differences. In this region, mean pixel shifts caused by local B0 field inhomogeneities were reduced from 3.47±1.22 mm to 1.35±0.44 mm and 0.99±0.30 mm using first and second order shimming respectively. This was for a bandwidth of 122 Hz/pixel and an in-plane voxel size of 1×1 mm2.  Also examined in Study II as in Study I was the dosimetric effect of geometric distortions on 21 Head and Neck cancer treatment plans. The dose difference in D50 at the PTV between distorted CT and real CT plans was less than 1.0%.

    In conclusion, the effect of MR geometric distortions on dose plans was small. Generally, we found patient-induced susceptibility distortions were larger compared with residual system distortions at all delineated structures except the external contour. This information will be relevant when setting margins for treatment volumes and organs at risk.  

    The current practice of characterizing MR geometric distortions utilizing spatial accuracy phantoms alone may not be enough for an MR-only radiotherapy workflow. Therefore, measures to mitigate patient-induced susceptibility effects in clinical practice such as patient-specific correction algorithms are needed to complement existing distortion reduction methods such as high acquisition bandwidth and shimming.

  • 35.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Medical Radiation Physics, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Quantifying the effect of 3T MRI residual system and patient-induced susceptibility distortions on radiotherapy treatment planning for prostate cancer2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 100, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of magnetic resonance system- and patient-induced susceptibility distortions from a 3T scanner on dose distributions for prostate cancers.

    Methods and Materials: Combined displacement fields from the residual system and patient-induced susceptibility distortions were used to distort 17 prostate patient CT images. VMAT dose plans were initially optimized on distorted CT images and the plan parameters transferred to the original patient CT images to calculate a new dose distribution.

    Results: Maximum residual mean distortions of 3.19 mm at a radial distance of 25 cm and maximum mean patient-induced susceptibility shifts of 5.8 mm were found using the lowest bandwidth of 122 Hz per pixel. There was a dose difference of <0.5% between distorted and undistorted treatment plans. The 90% confidence intervals of the mean difference between the dCT and CT treatment plans were all within an equivalence interval of (−0.5, 0.5) for all investigated plan quality measures.

    Conclusions: Patient-induced susceptibility distortions at high field strengths in closed bore magnetic resonance scanners are larger than residual system distortions after using vendor-supplied 3-dimensional correction for the delineated regions studied. However, errors in dose due to disturbed patient outline and shifts caused by patient-induced susceptibility effects are below 0.5%.

  • 36. Adler, Sara
    et al.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lindh, Johan
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Symptoms and risk factors of Cryptosporidium hominis infection in children: data from a large waterborne outbreak in Sweden2017In: Parasitology Research, ISSN 0932-0113, E-ISSN 1432-1955, Vol. 116, no 10, p. 2613-2618Article in journal (Refereed)
    Abstract [en]

    Cryptosporidium is a major cause of diarrheal disease worldwide. In developing countries, this infection is endemic and in children, associated with growth faltering and cognitive function deficits, with the most severe impact on those aged <2 years. Little has been reported about symptoms and risk factors for children in industrialized countries, although the disease incidence is increasing in such regions. In November 2010, a large waterborne outbreak of C. hominis occurred in the city of Östersund in Sweden. Approximately 27,000 of the 60,000 inhabitants were symptomatic. We aimed to describe duration of symptoms and the risk factors for infection with C. hominis in children aged <15 years in a Western setting. Within 2 months after a boil water advisory, a questionnaire was sent to randomly selected inhabitants of all ages, including 753 children aged <15 years. Those with ≥3 loose stools/day were defined as cases of diarrhoea. The response rate was 70.3%, and 211 children (39.9%) fulfilled the case definition. Mean duration of diarrhoea was 7.5 days (median 6, range 1-80 days). Recurrence, defined as a new episode of diarrhoea after ≥2 days of normal stools, occurred in 52.5% of the cases. Significant risk factors for infection, besides living within the distribution area of the contaminated water plant, included a high level of water consumption, male sex, and a previous history of loose stools. The outbreak was characterized by high attack and recurrence rates, emphasizing the necessity of water surveillance to prevent future outbreaks.

  • 37.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Clinical studies and chemical pathology in normal aging and dementia of Alzheimer type1980Doctoral thesis, comprehensive summary (Other academic)
  • 38. Affognon, H.
    et al.
    Mburu, P.
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, S.
    Ahlm, C.
    Sang, R.
    Evander, M.
    Sociocultural differences affect Rift Valley fever exposureManuscript (preprint) (Other academic)
  • 39. Affognon, Hippolyte
    et al.
    Mburu, Peter
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, Sarah
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sang, Rosemary
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, article id e0005405Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

  • 40. Afif, Haitham
    et al.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Hospital.
    Sjödén, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Hospital.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Hospital.
    Do bisphosphonate-related atypical femoral fractures and osteonecrosis of the jaw affect the same group of patients?: a pilot study2014In: Orthopedic Reviews, ISSN 2035-8237, E-ISSN 2035-8164, Vol. 6, article id 5067Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates (BPs) are commonly used drugs in clinical practice. In this pilot study, we investigated whether bisphosphonate-related atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) occurred simultaneously in the same group of patients. Six ONJ patients were examined by an orthopedic surgeon and 5 AFF patients were examined by a dentist to look for manifestations of simultaneous occurrence of AFF in ONJ patients and vice versa. The required radiological investigations and previous medical and dental records were available. No simultaneous occurrence of AFF and ONJ was found in the examined patients. In this pilot study with limited sample size, no manifestations of simultaneous occurrence of AFF and ONJ were found. This could be an indication that these complications have different pathophysiologies and affect different subgroups of patients on long-term BP treatment.

  • 41. Afset, J. E.
    et al.
    Larssen, K. W.
    Bergh, K.
    Larkeryd, A.
    Sjodin, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, M.
    Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 20112015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 19, p. 9-14, article id 21125Article in journal (Refereed)
    Abstract [en]

    In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.

  • 42. Agca, R.
    et al.
    Heslinga, S. C.
    Rollefstad, S.
    Heslinga, M.
    McInnes, B.
    Peters, M. J. L.
    Kvien, T. K.
    Dougados, M.
    Radner, H.
    Atzeni, F.
    Primdahl, J.
    Södergren, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Wållberg Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    van Rompay, J.
    Zabalan, C.
    Pedersen, T. R.
    Jacobsson, L.
    de Vlam, K.
    Gonzalez-Gay, M. A.
    Semb, A. G.
    Kitas, G. D.
    Smulders, Y. M.
    Szekanecz, Z.
    Sattar, N.
    Symmons, D. P. M.
    Nurmohamed, M. T.
    EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 1, p. 17-28Article, review/survey (Refereed)
    Abstract [en]

    Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

  • 43. Agewall, Stefan
    et al.
    Rydén, Lars
    Perk, Joep
    Rosengren, Annika
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Skellefteå Research Unit.
    Hellénius, Mai-Lis
    Ros, Inger
    Efterlyses: politik mot hjärtinfarkt2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 13-14, p. 664-Article in journal (Refereed)
  • 44. Agmon-Levin, Nancy
    et al.
    Damoiseaux, Jan
    Kallenberg, Cees
    Sack, Ulrich
    Witte, Torsten
    Herold, Manfred
    Bossuyt, Xavier
    Musset, Lucille
    Cervera, Ricard
    Plaza-Lopez, Aresio
    Dias, Carlos
    Sousa, Maria Jose
    Radice, Antonella
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Hultgren, Olof
    Viander, Markku
    Khamashta, Munther
    Regenass, Stephan
    Coelho Andrade, Luis Eduardo
    Wiik, Allan
    Tincani, Angela
    Ronnelid, Johan
    Bloch, Donald B.
    Fritzler, Marvin J.
    Chan, Edward K. L.
    Garcia-De la Torre, I.
    Konstantinov, Konstantin N.
    Lahita, Robert
    Wilson, Merlin
    Vainio, Olli
    Fabien, Nicole
    Sinico, Renato Alberto
    Meroni, Pierluigi
    Shoenfeld, Yehuda
    International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies2014In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.

  • 45.
    Agnvall, Ahlbin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Chronic exertional compartment syndrome in patients with diabetes mellitus type 1 - Outcome after surgery in 78 patients2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 46. Agostoni, C
    et al.
    Buonocore, G
    Carnielli, VP
    De Curtis, M
    Darmaun, D
    Decsi, T
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, ND
    Fusch, C
    Genzel-Boroviczeny, O
    Goulet, O
    Kalhan, SC
    Kolacek, S
    Koletzko, B
    Lapillonne, A
    Mihatsch, W
    Moreno, L
    Neu, J
    Poindexter, B
    Puntis, J
    Putet, G
    Rigo, J
    Riskin, A
    Salle, B
    Sauer, P
    Shamir, R
    Szajewska, H
    Thureen, P
    Turck, D
    van Goudoever, JB
    Ziegler, EE
    Enteral nutrient supply for preterm infants: commentary from the European society of paediatric gastroenterology, hepatology and nutrition committee on nutrition2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

  • 47. Agren, Per-Henrik
    et al.
    Tullberg, Tycho
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Wretenberg, Per
    Sayed-Noor, Arkan S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Post-traumatic in situ fusion after calcaneal fractures: A retrospective study with 7-28 years follow-up2015In: Foot and Ankle Surgery, ISSN 1268-7731, E-ISSN 1460-9584, Vol. 21, no 1, p. 56-59Article in journal (Refereed)
    Abstract [en]

    Background: In situ fusion as salvage operation after calcaneal fractures has been used. In this retrospective investigation, a group of in situ fused patients is analyzed with long-term follow-up.

    Methods: Twenty-nine patients with in situ single or multiple fusions performed between 1970 and 1990 were included. In 1998 these patients were examined with plain radiographs and computerized tomography (CT) scan of the affected foot. Also, a visual analogue score (VAS) for calcaneal fractures, short form health survey (SF-36), Olerud Molander score and American Orthopaedic Foot and Ankle society (AOFAS) hindfoot score were evaluated.

    Results: The plain radiographs and CT scan showed severe remaining deformities in these patients. The outcome parameters were generally poor and correlated to the degree of remaining deformity.

    Conclusions: Simple in situ fusion, without consideration of the deformity at hand, after a calcaneal fracture is not an adequate treatment and generally associated with poor outcome. (C) 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  • 48. Agreus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, no 5, p. 686-696Article in journal (Refereed)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 49. Agudo, Antonio
    et al.
    Bonet, Catalina
    Sala, Núria
    Muñoz, Xavier
    Aranda, Núria
    Fonseca-Nunes, Ana
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie Christine
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Grioni, Sara
    Quirós, J Ramón
    Molina, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Chamosa, Saioa
    Allen, Naomi E
    Khaw, Kay-Tee
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Numans, Mattijs E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Kaaks, Rudof
    Canzian, Federico
    Boeing, Heiner
    Meidtner, Karina
    Johansson, Mattias
    Umeå University, Faculty of Medicine. WHO, IARC, Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Manjer, Jonas
    Overvad, Kim
    Tjonneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Jenab, Mazda
    Fedirko, Veronika
    Offerhaus, G Johan A
    Riboli, Elio
    González, Carlos A
    Jakszyn, Paula
    Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2013In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, no 6, p. 1244-1250Article in journal (Refereed)
    Abstract [en]

    Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

  • 50. Agudo, Antonio
    et al.
    Cayssials, Valerie
    Bonet, Catalina
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Affret, Aurélie
    Fagherazzi, Guy
    Katzke, Verena
    Schübel, Ruth
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Peeters, Petra H.
    Weiderpass, Elisabete
    Skeie, Guri
    Nøst, Theresa H.
    Lasheras, Cristina
    Rodríguez-Barranco, Miguel
    Amiano, Pilar
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Ohlsson, Bodil
    Dias, Joana A.
    Nilsson, Lena M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Myte, Robin
    Khaw, Kay-Tee
    Perez-Cornago, Aurora
    Gunter, Marc
    Huybrechts, Inge
    Cross, Amanda J.
    Tsilidis, Kostas
    Riboli, Elio
    Jakszyn, Paula
    Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2018In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 107, no 4, p. 607-616Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

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