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1.
PLoS One ; 19(5): e0297182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768126

RESUMO

BACKGROUND: Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress. METHODS: Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program. RESULTS: 118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need. CONCLUSION: The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.


Assuntos
Amiloidose , Humanos , Feminino , Masculino , Idoso , Alemanha/epidemiologia , Amiloidose/terapia , Amiloidose/psicologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Qualidade de Vida , Cuidadores/psicologia , Diagnóstico Tardio
2.
Brain Nerve ; 76(5): 583-587, 2024 May.
Artigo em Japonês | MEDLINE | ID: mdl-38741500

RESUMO

AL amyloidosis, derived from amyloidogenic immunoglobulin light chains, is a common type of systemic amyloidosis. Peripheral neuropathy has been identified in 10%-40% of patients with systemic AL amyloidosis. Definitive diagnosis requires tissue biopsies, including skin, fat, and gastrointestinal samples, as well as amyloid typing. Disease-modifying therapies have been shown to improve patient survival and prevent progressive organ dysfunction.


Assuntos
Amiloidose , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Cadeias Leves de Imunoglobulina/metabolismo
3.
Hematol Oncol ; 42(3): e3270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590272

RESUMO

Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/terapia , Cadeias Leves de Imunoglobulina , Plasmócitos
5.
Rev Clin Esp (Barc) ; 224(5): 288-299, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614320

RESUMO

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Algoritmos , Cardiopatias/diagnóstico , Cardiopatias/terapia
6.
Curr Cardiol Rev ; 20(2): 72-81, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38682372

RESUMO

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A" (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/cirurgia , Amiloidose/terapia , Amiloidose/diagnóstico , Cardiomiopatias/cirurgia , Cardiomiopatias/terapia , Transplante de Coração
7.
Heart Lung Circ ; 33(4): 420-442, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570258

RESUMO

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.


Assuntos
Amiloidose , Cardiomiopatias , Consenso , Humanos , Nova Zelândia , Amiloidose/terapia , Amiloidose/diagnóstico , Austrália , Cardiomiopatias/terapia , Cardiomiopatias/diagnóstico
9.
Int J Mol Sci ; 25(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338870

RESUMO

Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and ß-amyloid peptide (Aß) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer's disease, respectively. Though crenezumab, an anti-Aß antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both Aß42 oligomers and AL fibrils with high binding affinities. It is capable of reversing Aß42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.


Assuntos
Doença de Alzheimer , Amiloidose , Anticorpos Monoclonais Humanizados , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Amiloide/metabolismo , Peptídeos beta-Amiloides/imunologia , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/uso terapêutico , Amiloidose/terapia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico
10.
Eur J Clin Invest ; 54(6): e14160, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38217112

RESUMO

Cardiac amyloidosis multidisciplinary team (MDT). We propose the creation of a multidisciplinary team (MDT) for cardiac amyloidosis in which internal medicine physicians could take a lead role in coordinating other specialists involved in patient care. Created with BioRender.com.


Assuntos
Amiloidose , Cardiomiopatias , Diagnóstico Precoce , Equipe de Assistência ao Paciente , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Cardiomiopatias/terapia , Cardiomiopatias/diagnóstico , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/terapia
12.
Alzheimers Dement ; 20(2): 1459-1464, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38085800

RESUMO

INTRODUCTION: Amyloid precursor protein (APP) transgenic mice are models of Alzheimer's disease (AD) amyloidosis, not all of AD. Diffuse, compacted, and vascular deposits in APP mice mimic those found in AD cases. METHODS: Most interventional studies in APP mice start treatment early in the process of amyloid deposition, consistent with a prevention treatment regimen. Most clinical trials treat patients with established amyloid deposits in a therapeutic treatment regimen. RESULTS: The first treatment to reduce amyloid and cognitive impairment in mice was immunotherapy. The APP mouse models not only predicted efficacy, but presaged the vascular leakage called ARIA. The recent immunotherapy clinical trials that removed amyloid and slowed cognitive decline confirms the utility of these early APP models when used in therapeutic designs. DISCUSSION: New mouse models of AD pathologies will add to the research armamentarium, but the early models have accurately predicted responses to amyloid therapies in humans.


Assuntos
Doença de Alzheimer , Amiloidose , Disfunção Cognitiva , Humanos , Camundongos , Animais , Doença de Alzheimer/terapia , Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Camundongos Transgênicos , Amiloidose/terapia , Amiloidose/metabolismo , Modelos Animais de Doenças , Peptídeos beta-Amiloides/metabolismo , Placa Amiloide/patologia
13.
Am J Hematol ; 99(2): 309-324, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38095141

RESUMO

DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. PROGNOSIS: N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively. THERAPY: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. FUTURE CHALLENGES: Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.


Assuntos
Amiloidose , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose/patologia , Prognóstico , Cadeias Leves de Imunoglobulina
14.
Pacing Clin Electrophysiol ; 47(1): 149-155, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055612

RESUMO

BACKGROUND: Conventional right ventricle (RV) pacemaker stimulation has been associated with worse clinical outcomes in patients with cardiac amyloidosis (CA). Left bundle branch area pacing (LABPP) has been suggested as a promising alternative. We sought to assess the safety, feasibility, and outcomes of LABPP in patients with CA. METHODS: We retrospectively analyzed echocardiography and pacing parameters and clinical outcomes in 23 consecutive patients with CA and LBBAP implanted from June 2020 to October 2022. RESULTS: LBBAP was successfully performed in 22 over 23 patients (19 male, 78.6 ± 11.7 years, 20 ATTR, mean LVEF 45.5 ± 16.2%). After the procedure, 9 patients showed Qr pattern and 11 a qR pattern in V1 on ECG. Average procedure time was 67 ± 28 min. After 7.7 ± 5.2 months follow-up, no procedure-related complications had occurred. Although, a significant reduction in QRS width (p = .001) was achieved, we did not observe significant changes in LVEF and Nt ProBNP at 6 months of follow-up. Pacing parameters were stable during follow-up: LBB capture threshold and R wave amplitude were 1.0 ±  0.5 V and 10.6 ± 6.0 mV versus 0.8 ±  0.1 V, p = .21 and 10.6 ± 5.1 mV (p = .985) at follow up. CONCLUSION: LBBAP is safe and feasible pacing technique for patients with CA. LBBAP is associated with significant narrowing of QRSd without worsening in LVEF and Nt-proBNP.


Assuntos
Amiloidose , Septo Interventricular , Humanos , Masculino , Estudos de Viabilidade , Estudos Retrospectivos , Amiloidose/terapia , Ventrículos do Coração , Eletrocardiografia , Estimulação Cardíaca Artificial , Fascículo Atrioventricular , Resultado do Tratamento
17.
Turk Patoloji Derg ; 40(1): 1-9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38111336

RESUMO

Cardiac amyloidosis is a type of amyloidosis that deserves special attention as organ involvement significantly worsens the prognosis. Cardiac amyloidosis can be grouped under three main headings: immunoglobulin light chain (AL) amyloidosis that is dependent on amyloidogenic monoclonal light chain production; hereditary Transthyretin (TTR) amyloidosis that results from accumulation of mutated TTR; and wild-type (non-hereditary) TTR amyloidosis formerly known as senile amyloidosis. Although all three types cause morbidity and mortality due to severe heart failure when untreated, they contain differences in their pathogenesis, clinical findings, and treatment. In this article, the clinical features, pathogenesis, diagnosis, and treatment methods of cardiac amyloidosis will be explained with an overview, and an awareness will be raised in the diagnosis of this disease.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Amiloidose/diagnóstico , Amiloidose/terapia , Prognóstico , Cadeias Leves de Imunoglobulina
18.
Nephrol Ther ; 19(7): 594-599, 2023 12 20.
Artigo em Francês | MEDLINE | ID: mdl-38073243

RESUMO

Introduction: Solitary plasmacytoma is a rare, localized malignancy. Bone localizations are the most common. Extramedullary plasmacytomas are much rarer. They are most often in the upper respiratory tract and can be complicated by amyloidosis. Here is an original report of a mediastinal extramedullary plasmacytoma revealed by type AA renal amyloidosis. Case presentation: We present the case of a 52-year-old patient with mediastinal extramedullary plasmocytoma diagnosed by renal failure due to type AA renal amyloidosis. Treatment was based on surgery with chemotherapy based on prednisone and melphalan. The patient presented end-stage renal failure that required hemodialysis at discharge. Conclusion: Extramedullary plasmacytoma is a rare tumour that may be associated with amyloidosis, usually type AL. To our knowledge, its association with AA amyloidosis has not been reported in the literature. Treatment is based on surgery combined with radiotherapy or chemotherapy.


Introduction: Le plasmocytome solitaire est une tumeur maligne rare localisée. Les localisations osseuses sont les plus fréquentes. Les plasmocytomes extra­médullaires (PEM) sont beaucoup plus rares, localisés le plus souvent au niveau des voies respiratoires supérieures. Présentation du cas: Nous rapportons une observation de PEM médiastinal révélé par une insuffisance rénale en rapport avec amylose rénale de type AA chez un patient âgé de 52 ans. Le traitement a comporté une tumorectomie de la masse associée à une chimiothérapie. Sur le plan rénal, le patient était au stade d'insuffisance rénale terminale nécessitant le recours à l'hémodialyse chronique. Conclusion: Le PEM est une tumeur rare pouvant se compliquer d'une amylose le plus souvent de type AL. Son association à une amylose AA n'a pas été rapportée auparavant à notre connaissance. Le traitement est basé surtout sur la chirurgie associée à une radiothérapie ou chimiothérapie.


Assuntos
Amiloidose , Plasmocitoma , Insuficiência Renal , Humanos , Pessoa de Meia-Idade , Plasmocitoma/complicações , Plasmocitoma/diagnóstico , Plasmocitoma/terapia , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/terapia , Proteína Amiloide A Sérica , Melfalan
19.
Ther Adv Cardiovasc Dis ; 17: 17539447231216318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099406

RESUMO

Cardiac amyloidosis (CA) is a condition caused by extracellular deposition of amyloid fibrils in the heart. It is an underdiagnosed disease entity which can present with a variety of cardiac and non-cardiac manifestations. Diagnosis usually follows an initial suspicion based on clinical evaluation or imaging findings before confirmation with subsequent imaging (echocardiography, cardiac magnetic resonance imaging, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy) in combination with biochemical screening for monoclonal dyscrasia (serum free light chains and serum and urine electrophoresis) and/or histology (bone marrow trephine, fat or endomyocardial biopsy). More than 95% of CA can be classified as either amyloid light-chain (AL) CA or amyloid transthyretin (ATTR) CA; these two conditions have very different management strategies. AL-CA, which may be associated with multiple myeloma, can be managed with chemotherapy agents, autologous stem cell transplantation, cardiac transplant and supportive therapies. For ATTR-CA, there is increasing importance in making an early diagnosis because of novel treatments in development, which have transformed this once incurable disease to a potentially treatable disease. Timely diagnosis is crucial as there may only be a small window of opportunity where patients can benefit from treatment beyond which therapies may be less effective. Reviewing the existing patient pathway provides a basis to better understand the complexities of real-world activities which may be important to help reduce missed opportunities related to diagnosis and treatment for patients with CA. With healthcare provider interest in improving the care of patients with CA, the development of an optimal care pathway for the condition may help reduce delays in diagnosis and treatment and thus enhance patient outcomes.


Assuntos
Amiloidose , Cardiomiopatias , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Transplante Autólogo , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Ecocardiografia , Amiloide , Diagnóstico Precoce , Proteínas Amiloidogênicas
20.
Glob Heart ; 18(1): 63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028963

RESUMO

Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of heart failure and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CA, which is now possible without recourse to endomyocardial biopsy in around 70% of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CA and more accurate prognostic stratification. Therapies able to slow or halt ATTR-CA progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional heart failure medications. A wide horizon of possibilities is unfolding and awaits discovery.


Assuntos
Amiloidose , Cardiomiopatias , Insuficiência Cardíaca , Humanos , Pré-Albumina/genética , Amiloidose/diagnóstico , Amiloidose/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Prognóstico , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia
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