Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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AGel amyloidosis is a dominantly inherited systemic amyloidosis caused by mutations p. D214N or p. D214Y resulting in gelsolin amyloid (AGel) formation. ⋯ The elastin of elastic fibres in AGel patients was strongly decreased compared to controls. MMP-9 was expressed at lower and TGFβ at higher levels in AGel patients than in controls. The accumulation of amyloid fibrils with severe elastolysis characterises both dermal and vascular derangement in AGel amyloidosis.
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Background: Patients with transthyretin (TTR) cardiac amyloidosis demonstrate cardiac cachexia with progression of their cardiomyopathy, which is characterised by malnutrition and a heightened inflammatory state. How best to measure this condition is less well characterised. We investigated differences in survival among patients with ATTR cardiac amyloidosis by nutritional status as defined by modified BMI (mBMI) and by inflammatory state as defined by serum uric acid. ⋯ Serum uric acid was a univariate predictor of death (HR 1.27 per 1 mg/dL, 95% CI 1.114-1.455, p < .001). In multivariate Cox analysis, this association remained significant (HR 1.31 per 1 mg/dL increase, 95% CI 1.096-1.560, p = .003) as well as in a separate stepwise model controlling for potential confounders including daily diuretic use, uric acid lowering therapy, and renal dysfunction. Conclusions: Both nutritional status as measured by mBMI and inflammation as measured by serum uric acid are associated with survival in patients with TTR cardiac amyloidosis however only serum uric acid is an independent predictor of death.
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The Curated Protein Aggregation Database (CPAD) is a manually curated and open-access database dedicated to providing comprehensive information related to mechanistic, kinetic and structural aspects of protein and peptide aggregation. The database has been updated to CPAD 2.0 by significantly expanding datasets and improving the user-interface. ⋯ This database will help the scientific community (a) by facilitating research leading to improved understanding of protein aggregation, (b) by helping develop, validate and benchmark mechanistic and kinetic models of protein aggregation, and (c) by assisting experimentalists with design of their investigations and dissemination of data generated by their studies. CPAD 2.0 can be accessed at https://web.iitm.ac.in/bioinfo2/cpad2/index.html.
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Background: Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) is a rare life-threatening disease that imposes considerable mortality and morbidity associated with increased costs, high social support and productivity losses. This study aims to estimate the societal costs and burden of ATTRv-PN. Methods: A cost-of-illness (COI) and burden of disease model were specified from a societal perspective, using a prevalence-based approach. ⋯ A total of 2056 DALYs were lost, 26% due to disability and 74% due to death. Conclusions: Annual costs and burden of ATTRv-PN were considerable but within the range of other rare diseases. Policies and public interventions to prevent and reduce the burden of disease should be prioritised, since patients experience excess morbidity, mortality and total costs will likely increase in the future.
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Peripheral nerve involvement in immunoglobulin light chain (AL) amyloidosis is common, characterised by severe progressive mixed neuropathy with autonomic dysfunction but there is limited data on the implications and the characteristics of small nerve fibres dysfunction (SNFD). The aim of our prospective study was to evaluate SNFD and its clinical implications in newly diagnosed AL patients. Twenty-three consecutive patients (10 male, mean age 61.78 years) and 21 age- and gender-matched healthy controls (8 male, mean age 61.28 years) underwent clinical evaluation and standard nerve conduction studies (NCS), baroreflex sensitivity (BRS) test, quantitative sensory testing (QST) and skin biopsy at the lower leg for measuring the density of the nerve fibres innervating the epidermis (IENFD). ⋯ BRS index significantly correlated with the IENFD and the QST results while low IENFD was associated with significantly poorer survival. Our study provides new insights and also an initial evaluation of new tools for assessment of the involvement of autonomic and small nerve fibres in AL amyloidosis. These findings also appear to have prognostic implications.