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Expert Review of Proteomics Sep 2019: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is... (Review)
Review
: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is essential in determining the causative protein and initiating proper treatment. Mass spectrometry-based proteomics is currently the most sensitive and accurate means of typing amyloid. : Amyloidosis can be systemic or localized, acquired or hereditary, and can affect any organ or tissue. Diagnosis requires biopsy, histological analysis, and typing of the causative protein to determine treatment. The kidneys are the most commonly affected organ in systemic disease. Fibrinogen alpha chain amyloidosis (AFib) is the most prevalent form of hereditary renal amyloidosis. Select mutations in the fibrinogen Aα (FGA) gene lead to AFib. : Mass spectrometry is currently the most specific and sensitive method for amyloid typing. Identification of the mutated fibrinogen alpha chain can be difficult in the case of 'private' frameshift mutations, which dramatically change the sequences of the expressed fibrinogen alpha chain. A combination of expert pathologist review, mass spectrometry, and gene sequencing can allow for confident diagnosis and determination of the fibrinogen alpha chain mutated sequence.
Topics: Amyloid; Amyloidosis; Fibrinogen; Humans; Kidney; Mass Spectrometry; Mutation; Proteomics
PubMed: 31443619
DOI: 10.1080/14789450.2019.1659137 -
JACC. Cardiovascular Imaging Nov 2019Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes... (Review)
Review
Interstitial heart disease, whether primarily from myocardial fibrosis or cardiac amyloidosis, indicates excess protein accumulation in the interstitium and constitutes a major source of heart failure with excess cardiac morbidity and mortality. Myocardial fibrosis (defined as excess myocardial collagen concentration that distorts myocardial architecture) is prevalent and causes cardiac symptoms and ultimately adverse cardiac events, such as heart failure, arrhythmia, and death. Conversely, cardiac amyloidosis is far less prevalent than myocardial fibrosis but represents a more extreme form of interstitial heart disease with marked interstitial expansion, profound architectural distortion, and then rapid clinical decline. Myocardial extracellular volume measures fundamentally advance the understanding of myocardium and specifically highlights the role of the interstitium. Rather than conceptualizing myocardium as a homogenous tissue, dichotomizing the myocardium into its interstitial (including the microvasculature) and cardiomyocyte phenotypes promotes additional understanding of heart failure pathophysiology that may spur the development of more effective therapies.
Topics: Amyloidosis; Cardiomyopathies; Disease Progression; Extracellular Space; Fibrosis; Heart Failure; Humans; Myocardium; Prognosis; Ventricular Remodeling
PubMed: 31422140
DOI: 10.1016/j.jcmg.2019.04.025 -
Current Hematologic Malignancy Reports Aug 2021Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many... (Review)
Review
PURPOSE OF REVIEW
Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available.
RECENT FINDINGS
New imaging methods have proven to be considerably valuable in the identification of cardiac amyloid infiltration. For treating clinicians, a diagnostic algorithm for patients with suspected amyloidosis with or without cardiomyopathy is shown to help classify disease and to direct appropriate genetic testing and management. For patients with light chain disease, recently introduced treatments adopted from multiple myeloma therapies have significantly extended progression-free and overall survival as well as organ response. In addition, new medical interventions are now available for those with transthyretin amyloidosis. Although cardiac amyloidosis contributes significantly to the morbidity and mortality associated with systemic disease, new tools are available to assist with diagnosis, prognosis, and management.
Topics: Amyloidosis; Cardiomyopathies; Humans
PubMed: 34106429
DOI: 10.1007/s11899-021-00626-4 -
European Heart Journal Dec 2022To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological...
AIMS
To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors.
METHODS AND RESULTS
In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01).
CONCLUSIONS
Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.
Topics: Humans; Amyloidosis; Magnetic Resonance Imaging; Immunoglobulin Light-chain Amyloidosis; Heart; Prognosis; Magnetic Resonance Spectroscopy; Myocardium; Magnetic Resonance Imaging, Cine; Predictive Value of Tests
PubMed: 36239754
DOI: 10.1093/eurheartj/ehac363 -
Journal of the American College of... Mar 2024Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most... (Review)
Review
Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis. Amyloid histological typing can be performed using different techniques: mass spectrometry, immunohistochemistry, and immunoelectron microscopy. This review describes which patients require histological confirmation of cardiac amyloidosis along with when and how to type amyloid deposits in histologic specimens. Furthermore, it covers the characteristics and limitations of the different typing methods that are available in clinical practice.
Topics: Humans; Plaque, Amyloid; Amyloidosis; Amyloid; Heart Failure; Immunohistochemistry; Amyloidogenic Proteins; Prealbumin; Amyloid Neuropathies, Familial; Cardiomyopathies
PubMed: 38479957
DOI: 10.1016/j.jacc.2024.01.010 -
International Journal of Molecular... Mar 2023Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac... (Review)
Review
Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thought to be underdiagnosed, which delays necessary therapeutic procedures, diminishing quality of life and impairing clinical prognosis. The diagnostic work-up for cardiac amyloidosis begins with the identification of clinical features, electrocardiographic and imaging findings suggestive or compatible with cardiac amyloidosis, and often requires the histological demonstration of amyloid deposition. One approach to overcome the difficulty of an early diagnosis is the use of automated diagnostic algorithms. Machine learning enables the automatic extraction of salient information from "raw data" without the need for pre-processing methods based on the a priori knowledge of the human operator. This review attempts to assess the various diagnostic approaches and artificial intelligence computational techniques in the detection of cardiac amyloidosis.
Topics: Humans; Artificial Intelligence; Quality of Life; Amyloidosis; Amyloid; Machine Learning; Cardiomyopathies
PubMed: 36982754
DOI: 10.3390/ijms24065680 -
Respiratory Care Jan 2020Diffuse cystic lung diseases (DCLDs) are a group of diverse pulmonary disorders with varying pathophysiology that are characterized by the presence of thin-walled,... (Review)
Review
Diffuse cystic lung diseases (DCLDs) are a group of diverse pulmonary disorders with varying pathophysiology that are characterized by the presence of thin-walled, air-filled spaces within lung parenchyma. High-resolution computed tomography plays a crucial role in the evaluation of DCLDs, and cyst characteristics such as morphology, distribution, and the presence of other associated radiologic findings can help distinguish between different DCLDs. DCLDs can be classified according to their underlying pathophysiology as neoplastic, genetic, lymphoproliferative, infectious, associated with other forms of interstitial lung disease, or related to smoking. In this review we will provide a clinical overview on the most common DCLDs that are encountered in clinical practice: lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, and lymphoid interstitial pneumonia/follicular bronchiolitis, with a focus on practical aspects that can help clinicians in the optimal diagnosis and management of patients with DCLDs.
Topics: Amyloidosis; Birt-Hogg-Dube Syndrome; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Lung; Lung Diseases; Lung Diseases, Interstitial; Lymphangioleiomyomatosis; Smoking; Tomography, X-Ray Computed
PubMed: 31615921
DOI: 10.4187/respcare.07117 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2023Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common...
BACKGROUND
Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors.
MATERIAL AND METHODS
Electronic searches were undertaken in five databases supplemented by manual scrutiny.
RESULTS
A total of 111 studies were included with 158 individuals.
CONCLUSIONS
The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.
Topics: Humans; Female; Amyloidosis; Macroglossia; Multiple Myeloma; Tongue Diseases; Tongue
PubMed: 37330968
DOI: 10.4317/medoral.25761 -
American Journal of Primatology Nov 2021While humans exhibit a significant degree of neuropathological changes associated with deficits in cognitive and memory functions during aging, non-human primates (NHP)... (Review)
Review
While humans exhibit a significant degree of neuropathological changes associated with deficits in cognitive and memory functions during aging, non-human primates (NHP) present with more variable expressions of pathological alterations among individuals and species. As such, NHP with long life expectancy in captivity offer an opportunity to study brain senescence in the absence of the typical cellular pathology caused by age-related neurodegenerative illnesses commonly seen in humans. Age-related changes at neuronal population, single cell, and synaptic levels have been well documented in macaques and marmosets, while age-related and Alzheimer's disease-like neuropathology has been characterized in additional species including lemurs as well as great apes. We present a comparative overview of existing neuropathologic observations across the primate order, including classic age-related changes such as cell loss, amyloid deposition, amyloid angiopathy, and tau accumulation. We also review existing cellular and ultrastructural data on neuronal changes, such as dendritic attrition and spine alterations, synaptic loss and pathology, and axonal and myelin pathology, and discuss their repercussions on cellular and systems function and cognition.
Topics: Aging; Alzheimer Disease; Animals; Brain; Cerebral Amyloid Angiopathy; Primates
PubMed: 34255875
DOI: 10.1002/ajp.23299 -
Haematologica Dec 2023Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils...
Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils in organs. The lack of suitable models has hindered the investigation of the disease mechanisms. Our aim was to establish AL LC-producing plasma cell lines and use them to investigate the biology of the amyloidogenic clone. We used lentiviral vectors to generate cell lines expressing LC from patients suffering from AL amyloidosis. The AL LC-producing cell lines showed a significant decrease in proliferation, cell cycle arrest, and an increase in apoptosis and autophagy as compared with the multiple myeloma LC-producing cells. According to the results of RNA sequencing the AL LC-producing lines showed higher mitochondrial oxidative stress, and decreased activity of the Myc and cholesterol pathways. The neoplastic behavior of plasma cells is altered by the constitutive expression of amyloidogenic LC causing intracellular toxicity. This observation may explain the disparity in the malignant behavior of the amyloid clone compared to the myeloma clone. These findings should enable future in vitro studies and help delineate the unique cellular pathways of AL, thus expediting the development of specific treatments for patients with this disorder.
Topics: Humans; Plasma Cells; Cell Survival; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Amyloid; Immunoglobulin Light Chains; Multiple Myeloma
PubMed: 37381778
DOI: 10.3324/haematol.2022.282484