| 11. |
- Gerdle, Björn, 1953-, et al.
(author)
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Plasma protein patterns are strongly correlated with pressure pain thresholds in women with chronic widespread pain and in healthy controls-an exploratory case-control study
- 2020
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In: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 99:22
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Journal article (peer-reviewed)abstract
- Chronic widespread pain (CWP) is a complex pain condition characterized by generalized musculoskeletal pain and often associated with other symptoms. An important clinical feature is widespread increased pain sensitivity such as lowered pain thresholds for mechanical stimuli (pressure pain thresholds [PPT]). There is a growing interest in investigating the activated neurobiological mechanisms in CWP, which includes fibromyalgia. In CWP, strong significant correlations have been found between muscle protein patterns and PPT. This explorative proteomic study investigates the multivariate correlation pattern between plasma proteins and PPT in CWP and in healthy controls (CON). In addition, this study analyses whether the important proteins for PPT differ between the 2 groups. Using 2-dimensional gel electrophoresis, we analyzed the plasma proteome of the CWP (n = 15) and the CON (n = 23) and proteins were identified using mass spectrometry. For both the CWP and the CON, the associations between the identified proteins and PPT were analyzed using orthogonal partial least square in 2 steps. Significant associations between certain plasma proteins and PPT existed both in CWP (R-2 = 0.95;P = .006) and in CON (R-2 = 0.89;P < .001). For both groups of subjects, we found several proteins involved in PPT that reflect different biological processes. The plasma proteins as well as the biological processes involved in PPT differed markedly between the 2 groups of subjects. This study suggests that plasma protein patterns are associated with pain thresholds in CWP. Using the plasma proteome profile of CWP to study potential biomarker candidates could provide a snapshot of ongoing systemic mechanisms in CWP.
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| 12. |
- Gerdle, Björn, et al.
(author)
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Plasma proteins from several components of the immune system differentiate chronic widespread pain patients from healthy controls - an exploratory case-control study combining targeted and non-targeted protein identification
- 2022
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In: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 101:46
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Journal article (peer-reviewed)abstract
- Chronic widespread pain (CWP), including fibromyalgia (FM), is characterized by generalized musculoskeletal pain and hyperalgesia. Plasma proteins from proteomics (non-targeted) and from targeted inflammatory panels (cytokines/chemokines) differentiate CWP/FM from controls. The importance of proteins obtained from these two sources, the protein-protein association network, and the biological processes involved were investigated. Plasma proteins from women with CWP (n = 15) and CON (n = 23) were analyzed using two-dimensional gel electrophoresis analysis and a multiplex proximity extension assay for analysis of cytokines/chemokines. Associations between the proteins and group were multivarietly analyzed. The protein-protein association network and the biological processes according to the Gene Ontology were investigated. Proteins from both sources were important for group differentiation; the majority from the two-dimensional gel electrophoresis analysis. 58 proteins significantly differentiated the two groups (R-2 = 0.83). A significantly enriched network was found; biological processes were acute phase response, complement activation, and innate immune response. As with other studies, this study shows that plasma proteins can differentiate CWP from healthy subjects. Focusing on cytokines/chemokines is not sufficient to grasp the peripheral biological processes that maintain CWP/FM since our results show that other components of the immune and inflammation systems are also highly significant.
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| 13. |
- Gerdle, Björn, et al.
(author)
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Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples
- 2017
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In: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 96:9
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Journal article (peer-reviewed)abstract
- This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain CWP) patients compared to healthy controls CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel 92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects R-2=0.58, Q(2)=0.37, analysis of variance of cross-validated predictive residuals P=0.006). It was not possible to significantly regress pain thresholds within each group CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator.
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| 14. |
- Gordon, Max, et al.
(author)
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Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty: A Nationwide Cohort Study.
- 2016
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In: Medicine. - 1536-5964 .- 0025-7974. ; 95:6
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Journal article (peer-reviewed)abstract
- Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery.A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n=270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow-up time was 10 years (range, 7-21).The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events.During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11).Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls.
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| 15. |
- Gustavsen, Alice, et al.
(author)
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Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome
- 2017
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In: Medicine. - 0025-7974. ; 96:11
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Journal article (peer-reviewed)abstract
- Rationale: Antiphospholipid syndrome (APS) in pregnancy may trigger the life-threatening catastrophic antiphospholipid syndrome (CAPS). Complement activation is implicated in the pathogenesis, and inhibition of complement factor C5 is suggested as an additional treatment option. Patient concerns, diagnosis and interventions: We present a pregnant patient treated with the C5-inhibitor eculizumab due to high risk of developing devastating APS-related complications. The complement inhibitory effects of the treatment were examined both in the patient and the premature infant. Outcomes: Complement activity in the mother recovered considerably faster than anticipated; however, no new thrombosis or CAPS developed during the last week of pregnancy or postpartum. Blood sampling from the umbilical vein and artery, and from the infant after delivery showed low complement activity; however, only 0.3% of the eculizumab concentration detected in the mother, consistent with low placental passage of eculizumab. Lessons: The data underscore the importance of close monitoring of complement inhibition and individualizing dosage regimens in pregnant patients receiving eculizumab. We document how traditional functional complement activity tests cannot assess the effect of eculizumab in premature infants due to the very low levels of complement factors detected in this infant born in gestational week 33. Only trace amounts of eculizumab passed the placenta. In conclusion, complement C5 inhibition might be a safe candidate treatment option for APS during pregnancy and delivery, and additionally, enables prolongation of pregnancy with important weeks.
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| 16. |
- Halvorsen, Marie, et al.
(author)
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Dimensions Underlying Measures of Disability, Personal Factors, and Health Status in Cervical Radiculopathy A Cross-Sectional Study
- 2015
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In: Medicine. - : LIPPINCOTT WILLIAMS and WILKINS. - 0025-7974 .- 1536-5964. ; 94:24
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Journal article (peer-reviewed)abstract
- This cross-sectional study sought to identify dimensions underlying measures of impairment, disability, personal factors, and health status in patients with cervical radiculopathy. One hundred twenty-four patients with magnetic resonance imaging-verified cervical radiculopathy, attending a neurosurgery clinic in Sweden, participated. Data from clinical tests and questionnaires on disability, personal factors, and health status were used in a principal-component analysis (PCA) with oblique rotation. The PCA supported a 3-component model including 14 variables from clinical tests and questionnaires, accounting for 73% of the cumulative percentage. The first component, pain and disability, explained 56%. The second component, health, fear-avoidance beliefs, kinesiophobia, and self-efficacy, explained 9.2%. The third component including anxiety, depression, and catastrophizing explained 7.6%. The strongest-loading variables of each dimension were "present neck pain intensity," "fear avoidance," and "anxiety." The three underlying dimensions identified and labeled Pain and functioning, Health, beliefs, and kinesiophobia, and Mood state and catastrophizing captured aspects of importance for cervical radiculopathy. Since the variables "present neck pain intensity," "fear avoidance," and "anxiety" had the strongest loading in each of the three dimensions; it may be important to include them in a reduced multidimensional measurement set in cervical radiculopathy.
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| 17. |
- Hellman, Urban, 1966-, et al.
(author)
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Genetic variants in cardiac calcification in Northern Sweden
- 2019
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In: Medicine. - : Wolters Kluwer. - 0025-7974 .- 1536-5964. ; 98:15
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Journal article (peer-reviewed)abstract
- Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.
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| 18. |
- Hogevik, Harriet, et al.
(author)
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Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study.
- 1995
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In: Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0025-7974. ; 74:6, s. 324-39
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Journal article (peer-reviewed)abstract
- A prospective study of the epidemiology of infective endocarditis (IE) in a well-defined urban population of 428,000 inhabitants during a 5-year period was carried out. All patients were treated in the same institution, and history, diagnostic procedures, and treatment were standardized. Of 233 consecutive suspected episodes of IE, 127 fulfilled the modified von Reyn criteria. After patients not living in the defined area were excluded, 99 episodes in 90 patients were analyzed in the epidemiologic part of the study. Of these, 33 episodes were definite endocarditis, verified by surgery or autopsy; 35 probable; and 31 possible endocarditis episodes. Another 34 episodes were found retrospectively and are included in the incidence calculation. The crude incidence was calculated to be 6.2/100,000 inhabitants per year, which is high compared to earlier studies. Adjusted to the population of Sweden, the incidence was 5.9/100,000 inhabitants per year. The annual incidence was higher for women, 6.6/100,000, than for men, 5.8/100,000. In the oldest age-group (80-89 years) the annual incidence was 22/100,000 in the prospective study and 30/100,000 if retrospective cases were included. Contrary to almost all other studies, we did not find a male predominance among our cases. Only 7% of patients were intravenous drug abusers, and 15% had a prosthetic valve. The most common bacteria were methicillin-susceptible Staphylococcus aureus (31%) and alpha-streptococci (28%); 12% of episodes were culture negative. The mortality from IE in the population was 1.4/100,000 inhabitants per year. A higher-than-expected incidence of IE was found, especially among older patients and women.
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| 19. |
- Jensen, Elisabeth Kjær, et al.
(author)
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A national center for persistent severe pain after groin hernia repair : Five-year prospective data
- 2019
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In: Medicine. - 0025-7974. ; 98:33
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Journal article (peer-reviewed)abstract
- Severe persistent pain after groin hernia repair impairs quality-of-life. Prospective, consecutive cohort study including patients with pain-related impairment of physical and social life. Relevant surgical records were obtained, and examinations were by standardized clinical and neurophysiological tests. Patients demonstrating pain sensitivity to pressure algometry in the operated groin underwent re-surgery, while patients with neuropathic pain received pharmacotherapy. Questionnaires at baseline (Q0) and at the 5-year time point (Q5Y) were used in outcome analyses of pain intensity (numeric rating scale [NRS] 0-10) and pain-related effect on the activity-of-daily-living (Activities Assessment Scale [AAS]). Data are mean (95% CI).Analyses were made in 172/204 (84%) eligible patients. In 54/172 (31%) patients re-surgery (meshectomy/selective neurectomy) was performed, while the remaining 118/172 (69%) patients received pharmacotherapy. In the re-surgery group, activity-related, and average NRS-scores at Q0 were 6.6 (5.6-7.9) and 5.9 (5.6-5.9), respectively. Correspondingly, NRS-scores at Q5Y was 4.1 (3.3-5.1) and 3.1 (2.3-4.0; Q0 vs. Q5Y: P < .0005), respectively. Although both groups experienced a significant improvement in AAS-scores comparing Q0 vs. Q5Y (re-surgery group: 28% (4-43%; P < .0001); pharmacotherapy group: 5% (0-11%; P = .005)) the improvement was significantly larger in the re-surgery group (P = .02).This 5-year cohort study in patients with severe persistent pain after groin hernia repair signals that selection to re-surgery or pharmacotherapy, based on examination of pain sensitivity, is associated with significant improvement in outcome. Analyzing composite endpoints, combining pain and physical function, are novel in exploring interventional effects.ClinicalTrials.gov Identifier NCT03713047.
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| 20. |
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