| 1. |
- Johansson, Åsa, et al.
(författare)
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Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
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Forskningsöversikt (refereegranskat)abstract
- Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
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| 2. |
- Rantapää-Dahlqvist, Solbritt, 1947-
(författare)
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What happens before the onset of rheumatoid arthritis?
- 2009
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Ingår i: Current Opinion in Rheumatology. - : Lippincott Williams & Wilkins, Inc. - 1040-8711 .- 1531-6963. ; 21:3, s. 272-278
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: To give an overview of publications on presence of autoantibodies, rheumatoid factor and anticitrullinated protein/peptide antibodies (ACPAs) and their relationships to genetic markers and soluble factors as indicators of immune activation and identified predating the onset of symptoms of rheumatoid arthritis (RA). RECENT FINDINGS: The development during recent years concerning autoantibodies with high specificity for RA, ACPAs, has confirmed previous findings of presence of autoantibodies, such as rheumatoid factors and antikeratin antibodies, years before disease onset. Particularly, ACPAs in combination with human leukocyte antigen-shared epitope alleles and PTPN22 1858T carriage increased the relative risks of developing RA compared with not having these factors. Both shared epitope alleles and 1858T variant seemed to contribute to development of ACPAs rather than independently contribute to RA. Soluble factors such as hypersensitive C-reactive protein, cytokines, cytokine receptors and chemokines are upregulated before disease onset, though, not as long antedating time as ACPAs and rheumatoid factors. SUMMARY: Presence of ACPAs and rheumatoid factors are present several years before disease onset suggesting a gradual process leading to the development of RA. Genetic markers such as shared epitope alleles and PTPN22 1858T variant increase the relative risk for disease development. Soluble immunological markers are also increased closer to the onset of symptoms indicating activation of the immune system.
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| 3. |
- Lammi, Mikko, 1961-, et al.
(författare)
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Nivelrikon välittäjäaineet [Mediators of osteoarthritis]
- 2008
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Ingår i: Duodecim. - 0012-7183. ; 124:16, s. 1876-1884
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Forskningsöversikt (refereegranskat)abstract
- Normaalissa rustossa vallitsee tasapainotila kudosta tuottavien ja hajottavien prosessien kesken, mutta nivelrikossa painopiste siirtyy katabolian suuntaan. Nivelrikon etiologiaa ei tunneta, mutta sen syntyyn liittyy joukko tekijöitä, jotka johtavat väliaineen lisääntyneeseen hajoamiseen ja vähentyneeseen väliainetuotantoon, rustosolujen apoptoosiin, muutoksiin rustonalaisessa luussa ja nivelkalvon tulehdukseen. Nivelrikkoa välittävistä liukoisista tekijöistä ovat parhaiten tunnettuja tulehdusta moduloivat sytokiinit ja niiden aktivoimat tekijät, kuten metalloproteinaasit ja aggrekanaasit. Myös typpioksidin ja eikosanoidien yhteys nivelrikkoon on hyvin osoitettu. Viimeaikaiset tutkimukset ovat tuoneet esiin myös monia uusia tekijöitä, joilla todennäköisesti on merkitystä nivelrikon patologiassa. Nämä löydökset antavat pohjaa uudenlaisille hoitostrategioille.
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| 4. |
- Laurell, Louise, 1959, et al.
(författare)
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Imaging in juvenile idiopathic arthritis with a focus on ultrasonography.
- 2013
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Ingår i: Clinical and experimental rheumatology. - 0392-856X .- 1593-098X. ; 31:1, s. 135-48
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Forskningsöversikt (refereegranskat)abstract
- Early therapeutic intervention and use of new highly efficacious treatments have improved the outcome in many patients with juvenile idiopathic arthritis (JIA), but have also led to the need for more precise methods to evaluate disease activity. In adult rheumatology, numerous studies have established the importance of magnetic resonance imaging (MRI) and ultrasonography (US), and MRI is considered the reference standard. Nevertheless, due to differences in disease characteristics and the unique features of the growing skeleton, the findings obtained in adults are not directly applicable to children and adolescents. For paediatric patients, US offers specific advantages over MRI, because it is non-invasive, does not require sedation or general anesthesia (which facilitates repeated examinations for follow-up), is quickly accessible bedside, and is easy to combine with clinical assessment (interactivity). Agitation of the patient is rarely a problem, and hence young children can be seated on a parent's lap or play while being examined, and multiple locations can be assessed during a single session. Furthermore, modern high-frequency US transducers used by experienced US examiners can provide unsurpassed resolution of the superficial musculoskeletal structures in children. US is also the best available technique for imaging guidance of steroid injections. Unfortunately, there are still no validated MRI or US scoring systems for evaluating inflammatory and joint damage abnormalities in JIA, and few US studies have been conducted. Sonographic assessment of disease activity has, however, been proven to be more informative than clinical examination and is also readily available at points of care. This review summarises the literature on imaging in JIA, focusing on US and the important role this technique will play in JIA in the future.
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| 5. |
- Heyde, Christoph-E, et al.
(författare)
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Pitfalls and complications in the treatment of cervical spine fractures in patients with ankylosing spondylitis.
- 2008
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Ingår i: Patient safety in surgery. - : Springer Science and Business Media LLC. - 1754-9493. ; 2
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Forskningsöversikt (refereegranskat)abstract
- Patients with ankylosing spondylitis are at significant risk for sustaining cervical spine injuries following trauma predisposed by kyphosis, stiffness and osteoporotic bone quality of the spine. The risk of sustaining neurological deficits in this patient population is higher than average. The present review article provides an outline on the specific injury patterns in the cervical spine, diagnostic algorithms and specific treatment modalities dictated by the underlying disease in patients with ankylosing spondylitis. An emphasis is placed on the risks and complication patterns in the treatment of these rare, but challenging injuries.
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| 6. |
- Yates, M., et al.
(författare)
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EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 75:9, s. 1583-1594
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Forskningsöversikt (refereegranskat)abstract
- In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.
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| 7. |
- Granath, Annika, 1979-, et al.
(författare)
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How is the patient perspective captured in ANCA-associated vasculitis research? An integrative review
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 2514-1775. ; 7:3
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: The aim was to describe how the patient perspective is captured in clinical research on ANCA-associated vasculitis (AAV).METHODS: This integrative review included 2149 publications found in four different databases and manual searches. After screening, 156 articles remained. All articles were sorted and categorized, and 77 original articles were analysed further.RESULTS: The patient perspective was captured with patient-reported outcome measures (PROMs), single-item questionnaires, project-specific questionnaires and interviews. The most common aspects measured were health-related quality of life, anxiety and depression, and fatigue, and the least common were lifestyle habits, relationships and self-management.CONCLUSION: The patient perspective was captured predominantly with generic PROMs and occasionally with a qualitative approach. AVV is a lifelong disease, and the results from this review show that not all aspects of importance to patients are covered with the PROMs used in research. Future studies should include the areas that are the most important for patients.
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| 8. |
- Hemminki, Kari, et al.
(författare)
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Autoimmune diseases and hematological malignancies : exploring the underlying mechanisms from epidemiological evidence
- 2020
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 64, s. 114-121
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Forskningsöversikt (refereegranskat)abstract
- Autoimmune diseases are characterized by the irregular functioning of the immune system that leads to the loss of tolerance to self-antigens. The underlying nature of autoimmune diseases has led to speculation that the risk of malignancy might be higher or lower in patients with such diseases. However, the rarity and heterogeneity of both autoimmune diseases and malignancies is the main challenge for systematic exploration of associations between autoimmune diseases and cancer. The nationwide usages of electronic health records in Sweden and other countries has created longitudinal clinical datasets of large populations, which are ideal for quantifying the associations as well as possible guidance concerning the underlying mechanisms. In this report, we firstly summarize the population-based epidemiological association studies between autoimmune diseases and subsequent hematological malignancies using data derived mainly from Swedish nationwide data. These include over one million cancer cases and approximately 500,000 patients with medically diagnosed autoimmune disease. We further discuss the underlying mechanisms that contribute to the observed association between autoimmune diseases and hematological malignancies, including shared genetics, environmental factors, medical treatments of autoimmune diseases as well as dysregulated immune function.
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| 9. |
- Lasselin, Julie, et al.
(författare)
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Sex differences in how inflammation affects behavior : What we can learn from experimental inflammatory models in humans
- 2018
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Ingår i: Frontiers in neuroendocrinology (Print). - : Elsevier BV. - 0091-3022 .- 1095-6808. ; 50, s. 91-106
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Forskningsöversikt (refereegranskat)abstract
- Human models demonstrate that experimental activation of the innate immune system has profound effects on brain activation and behavior, inducing fatigue, worsened mood and pain sensitivity. It has been proposed that inflammation is a mechanism involved in the etiology and maintenance of depression, chronic pain and long-term fatigue. These diseases show a strong female overrepresentation, suggesting that a better understanding of sex differences in how inflammation drives behavior could help the development of individualized treatment interventions. For this purpose, we here review sex differences in studies using experimental inflammatory models to investigate changes in brain activity and behavior. We suggest a model in which inflammation accentuates sex differences in brain networks and pre-existing vulnerability factors. This effect could render women more vulnerable to the detrimental effects of immune-to-brain communication over time. We call for systematic and large scale investigations of vulnerability factors for women in the behavioral response to inflammation.
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| 10. |
- Daugaard, C. L., et al.
(författare)
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The effects of weight loss on imaging outcomes in osteoarthritis of the hip or knee in people who are overweight or obese : a systematic review
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:1, s. 10-21
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Forskningsöversikt (refereegranskat)abstract
- Objective: To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied. Design: Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese. Results: From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip. Conclusion: We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.
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