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- Benson, Merrill D., et al.
(författare)
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Tissue biopsy for the diagnosis of amyloidosis : experience from some centres
- 2022
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 29:1, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.
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| 4. |
- Rosengren, Sara, 1978-
(författare)
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AL amyloidosis : Study of epidemiology, diagnosis and treatment with emphasis on heart involvement
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AL (immunoglobulin light chain) amyloidosis is often associated with delayed diagnosis and thereby high early mortality that is not overcome by contemporary treatment. There is a need for diagnostic methods promoting earlier diagnosis, especially in patients with cardiac involvement. Progress has been made in the treatment of AL amyloidosis and prolonged survival has been reported from specialized referral centers. However, population-based reports are scarce regarding epidemiology as well as treatment outcomes. Aims of this thesis were to increase the knowledge of the epidemiology of AL amyloidosis, investigate new imaging methods for early diagnosis and prognostication in cardiac amyloidosis (CA), and evaluate treatment options with focus on patients with cardiac involvement. In paper I we presented real-world long-term results of treatment with high dose chemotherapy for AL amyloidosis in Sweden. We could conclude that long overall survival (median 8.2 years, 95% CI 5.1-11.2) was reached with high dose chemotherapy, but with inferior outcomes in patients with cardiac involvement. Treatment related mortality was comparable to that reported from larger centers during this period and was decreasing from 23.8% to 7.8% during the studied time period.In paper II we studied the accuracy of PET with the amyloid binding tracer 11C-PIB for the diagnosis of CA. 11C-PIB PET showed high accuracy in detecting CA, and affinity was higher for AL compared to transthyretin amyloidosis. We concluded that 11C-PIB PET can be a useful method to rule in or out amyloidosis in patients with unexplained diastolic heart failure. Our results also indicated that 11C-PIB PET can detect CA at an earlier stage than echocardiography and might be a useful tool for early diagnosis.In paper III we studied the prognostic value of cardiac function parameters from 11C-acetate PET in CA. We found that reduced myocardial external efficiency was associated with inferior survival in CA patients. However, the strongest prognostic parameter was lowered ratio of forward stroke volume and left ventricular mass, which was the only independently prognostic parameter in multivariable analysis. Paper IV was a population-based epidemiological study in which we could determine the standardized incidence of systemic AL amyloidosis to 12.0 (95% CI 9.3-14.7) per million person-years for Uppsala County, without significant change during the period 2000-2020. The 5-year limited duration prevalence increased numerically, but without statistical significance. Prolonged overall survival was observed over time, and there was also a decrease in early mortality, indicating earlier diagnosis of especially patients with cardiac involvement.
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| 5. |
- Saunders, Charlie N., et al.
(författare)
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Search for AL amyloidosis risk factors using Mendelian randomization
- 2021
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:13, s. 2725-2731
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Tidskriftsartikel (refereegranskat)abstract
- In amyloid light chain (AL) amyloidosis, amyloid fibrils derived from immunoglobulin light chain are deposited in many organs, interfering with their function. The etiology of AL amyloidosis is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited by Mendelian randomization (MR) methodology to search for factors influencingALamyloidosis risk.Weperformed a 2-sample MR analyzing 72 phenotypes, proxied by 3461 genetic variants, and summary genetic data from a GWAS of 1129 AL amyloidosis cases and 7589 controls. Associations with a Bonferroni-defined significance level were observed for genetically predicted increased monocyte counts (P = 3.8 × 10-4) and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 × 10-5). Two other associations with the TNFRSF (members 6 and 19L) reached a nominal significance level. The association between genetically predicted decreased fibrinogen levels may be related to roles of fibrinogen other than blood clotting. be related to its nonhemostatic role. It is plausible that a causal relationship with monocyte concentration could be explained by selection of a light chain-producing clone during progression of monoclonal gammopathy of unknown significance toward AL amyloidosis. Because TNFRSF proteins have key functions in lymphocyte biology, it is entirely plausible that they offer a potential link to AL amyloidosis pathophysiology. Our study provides insight into AL amyloidosis etiology, suggesting high circulating levels of monocytes and TNFRSF proteins as risk factors.
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