Articles: amyloidosis.
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Review Guideline
Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group.
This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis. ⋯ The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients' fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed.
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Amyloidosis is a pathologic and clinical condition resulting from the accumulation of insoluble aggregates of misfolded proteins in tissues. Extracellular deposition of amyloid fibrils in the myocardium leads to cardiac amyloidosis, which is often overlooked as a cause of diastolic heart failure. Although cardiac amyloidosis was previously believed to have a poor prognosis, recent advances in diagnosis and treatment have emphasized the importance of early recognition and changed management of this condition. This article provides an overview of cardiac amyloidosis and summarizes current screening, diagnosis, evaluation, and treatment options.
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Cardiac amyloidosis is caused by abnormal extracellular deposition of insoluble fibrils in cardiac tissue. It can be fatal when untreated and is often underdiagnosed. Understanding the ethnic/racial differences in risk factors is critical for early diagnosis and treatment to improve clinical outcomes. ⋯ Our findings highlight significant ethnic/racial differences in risk factors and outcomes among amyloidosis-related US hospitalizations that can possibly be used for early detection, treatment, and better clinical outcomes.
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Observational Study
Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study.
Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. ⋯ These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.
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Systemic AL amyloidosis arises from the misfolding of patient-specific immunoglobulin light chains (LCs). Potential drivers of LC amyloid formation are mutational changes and post-translational modifications (PTMs). However, little information is available on the exact primary structure of the AL proteins and their precursor LCs. ⋯ Our data imply that mutational changes influence the surface charge properties of the VL and that common proteolytic processes are involved in the generation of the cleavage sites of AL proteins.