Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Factors associated with financial toxicity in patients with transthyretin amyloidosis: results from Amyloidosis Research Consortium's treatment affordability patient and caregiver survey.","authors":"Sabrina Rebello, Kristen Hsu, Jose Nativi-Nicolau, Chafic Karam, Martha Grogan, Isabelle Lousada, Mathew S Maurer","doi":"10.1080/13506129.2025.2462541","DOIUrl":"https://doi.org/10.1080/13506129.2025.2462541","url":null,"abstract":"<p><strong>Introduction: </strong>Transthyretin (ATTR) amyloidosis is an ultimately fatal disease. While approved therapies slow disease progression, the cost of care can be significant for patients. The objective of this survey was to describe the factors associated with financial toxicity of ATTR amyloidosis and the economic burden of care and treatment.</p><p><strong>Methods: </strong>The Amyloidosis Research Consortium (ARC) conducted an online survey in the United States for patients with ATTR amyloidosis and their caregivers. Financial toxicity was assessed using the COmprehensive Score for Financial Toxicity (COST). Multivariate linear regression was used to identify factors associated with financial toxicity controlling for key sociodemographic and patient characteristics.</p><p><strong>Results: </strong>Of 452 respondents, 249 (55%) reported financial toxicity. Respondents who reported financial toxicity predominantly had ATTRv amyloidosis, were younger, non-white, had a household income <$100,000, had multiple sources of insurance, and were less frequently retired. Respondents reported using several ways to offset the cost of treatment.</p><p><strong>Conclusions: </strong>Patients with ATTR amyloidosis experience significant financial distress that is comparable to patients with cancer, and as a result, many patients delay treatment or pay for treatment using savings and/or borrowing money. African American respondents (vs white) were significantly at risk.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-10"},"PeriodicalIF":5.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global patterns of amyloid typing: results of a survey by the International Society of Amyloidosis (ISA).","authors":"Hironobu Naiki, Mona Johnson, Kaylee Walters, Alexander Carpinteiro, M Teresa Cibeira, Anita D'Souza, Efstathios Kastritis, Mathew S Maurer, Lisa Mendelson, Giampaolo Merlini, Eli Muchtar, Giovanni Palladini, Eloisa Riva, Yoshiki Sekijima, Per Westermark, Shaji Kumar, Stefan Olaf Schönland","doi":"10.1080/13506129.2025.2462992","DOIUrl":"https://doi.org/10.1080/13506129.2025.2462992","url":null,"abstract":"<p><strong>Background: </strong>Accurate tissue typing in amyloidosis is essential to provide appropriate therapy for individual patients.</p><p><strong>Objective: </strong>To get a real-life overview of typing strategies worldwide.</p><p><strong>Methods: </strong>The International Society of Amyloidosis (ISA) performed an online questionnaire survey among ISA members. We prepared questionnaire sheets for referral institutions (Category 1; C1), institutions performing amyloid typing for internal requests only (C2), and institutions outsourcing amyloid typing to referral institutions (C3), respectively.</p><p><strong>Results: </strong>Seventy-six institutions participated in this survey, including C1 (<i>n</i> = 33), C2 (<i>n</i> = 20) and C3 (<i>n</i> = 23) institutions. Multiple typing methods were available across the responding institutions, including immunohistochemistry (85% of C1/C2 institutions), immunofluorescence microscopy (43%), genetic analysis (77%) and mass spectrometric analysis (42%). Commercial antibodies were used worldwide for immunohistochemistry. C1 institutions in Europe and Asia also used various in-house antibodies. Ninety-three percent of institutions performed genetic analysis of <i>TTR gene</i>, followed by <i>APOA1</i> (43%), <i>FGA</i>, <i>GSN</i>, <i>LYZ</i> (33%) and <i>APOA2</i> (31%). Hierarchical referral flows of mass spectrometric analysis, immunohistochemistry and genetic analysis were observed regionally and internationally. Globalization and centralization of referral flows were more prominent for mass spectrometric analysis.</p><p><strong>Conclusion: </strong>These data provide an assessment of the current state, enabling improvement in capabilities of amyloid typing worldwide and enhancing regional/international networks.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-6"},"PeriodicalIF":5.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluation of Mayo 2004 and revised Mayo 2012 staging in patients with AL amyloidosis in the era of new therapies.","authors":"Foteini Theodorakakou, Despina Fotiou, Vasiliki Spiliopoulou, Magdalini Migkou, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, Maria Roussou, Nikolaos Kanellias, Evangelos Eleutherakis-Papaiakovou, Eirini Solia, Asimina Papanikolaou, Charikleia Gakiopoulou, Julie Courraud, Panagiota-Efstathia Nikolaou, Stavroula Giannouli, Maria Gavriatopoulou, Evangelos Terpos, Meletios-Athanasios Dimopoulos, Efstathios Kastritis","doi":"10.1080/13506129.2025.2456790","DOIUrl":"https://doi.org/10.1080/13506129.2025.2456790","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-3"},"PeriodicalIF":5.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Previous surgery for lumbar spinal stenosis and association with amyloidosis and heart failure - A Danish nationwide study.","authors":"Navid Noory, Eva Havers-Borgersen, Adelina Yafasova, Oscar Westin, Mathew S Maurer, Lars Køber, Finn Gustafsson, Emil Fosbøl","doi":"10.1080/13506129.2025.2456802","DOIUrl":"https://doi.org/10.1080/13506129.2025.2456802","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac Amyloidosis (CA) is characterised by amyloid fibril deposits causing heart failure (HF). Lumbar spinal stenosis (LSS) is recognised as a potential red flag for CA, but the association remains underexplored in large-scale studies.</p><p><strong>Methods: </strong>This nationwide registry-based cohort study in Denmark included subjects ≥60 years with a history of LSS surgery. LSS patients were matched 1:1 with controls by age, sex, ischaemic heart disease, chronic obstructive lung disease, chronic kidney disease, diabetes, and atrial fibrillation.</p><p><strong>Results: </strong>A total of 44,548 LSS surgery patients and matched controls were included (median age 71.5 years, 56.2% women). The cumulative incidence of amyloidosis after 10 years was higher in the LSS group (0.16% vs. 0.08%, HR 2.29 [95% CI 1.46-3.60]) after adjustment for malignancy, hypertension, and liver disease. The cumulative incidence of HF after 10 years was 10.1% in LSS patients compared with 7.5% in controls (HR 1.28 [95% CI 1.22-1.35], <i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>In this nationwide cohort study, LSS surgery was associated with a significantly higher risk of amyloidosis and HF. Prospective studies are warranted to explore the association further.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-7"},"PeriodicalIF":5.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of the Columbia score for predicting outcomes in patients with transthyretin amyloid cardiomyopathy. Analysis of the Galician registry of cardiac amyloidosis.","authors":"Fausto De Andrés-Cardelle, Gonzalo Barge-Caballero, Manuel López-Pérez, Andrea López-López, Eva González-Babarro, Mario Gutiérrez-Feijoo, Raquel Bilbao-Quesada, Inés Gómez-Otero, Alfonso Varela-Román, Alberto Bouzas-Mosquera, María G Crespo-Leiro, Eduardo Barge-Caballero","doi":"10.1080/13506129.2025.2453231","DOIUrl":"https://doi.org/10.1080/13506129.2025.2453231","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the predictive value of the Columbia score in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).</p><p><strong>Methods: </strong>Observational study based in a prospective, multi-centre registry of patients with ATTR-CM recruited between January-2018 and December-2023 in 7 Spanish hospitals. The Baseline Columbia score was correlated by means of multivariable Cox's regression with study endpoints all-cause death and all-cause death or heart failure (HF) hospitalisation. Discriminative capacity was evaluated by means of Harrell's <i>C</i> statistics and area under 2-year time-dependent receiver-operator curves.</p><p><strong>Results: </strong>We studied 374 patients with ATTR-CM. Columbia score was independently associated with increased risk of all-cause death (adjusted HR per 1 point = 1.30, 95% CI 1.17-1.45) and all-cause death or HF hospitalisation (adjusted HR per 1 point = 1.38, 95% 1.26-1.50). The score showed moderate discriminative capacity for all-cause death (Harrell's <i>C</i> = 0.653) and all-cause death or HF hospitalisation (Harrell's <i>C</i> = 0.697). The area under the 2-year time-dependent receiver-operator curve was 0.594 for all-cause death and 0.669 for all-cause death or HF hospitalisation. Columbia's score was adequately calibrated for both outcomes.</p><p><strong>Conclusions: </strong>We studied the prognostic performance of the Columbia score in a Spanish prospective cohort of patients with ATTR-CM. The score showed adequate calibration and moderate discriminative capacity for predicting death and HF hospitalisations.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-9"},"PeriodicalIF":5.2,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/13506129.2024.2442810","DOIUrl":"10.1080/13506129.2024.2442810","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1"},"PeriodicalIF":5.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated AL-base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis.","authors":"Gareth J Morgan, Allison N Nau, Sherry Wong, Brian H Spencer, Yun Shen, Axin Hua, Matthew J Bullard, Vaishali Sanchorawala, Tatiana Prokaeva","doi":"10.1080/13506129.2024.2434899","DOIUrl":"10.1080/13506129.2024.2434899","url":null,"abstract":"<p><strong>Background: </strong>Each monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences drive amyloid deposition could facilitate faster diagnosis and lead to new treatments.</p><p><strong>Methods: </strong>Light chain sequences are collected in the AL-Base repository. Monoclonal sequences from AL amyloidosis, multiple myeloma and the healthy polyclonal immune repertoire were compared to identify differences in precursor gene use, mutation frequency and physicochemical properties.</p><p><strong>Results: </strong>AL-Base now contains 2,200 monoclonal light chain sequences from AL amyloidosis and other plasma cell dyscrasias. Sixteen germline precursor genes were enriched in AL amyloidosis, relative to multiple myeloma and the polyclonal repertoire. Two genes, <i>IGKV1-16</i> and <i>IGLV1-36</i>, were infrequently observed but highly enriched in AL amyloidosis. The number of mutations varied widely between light chains. AL-associated κ light chains harboured significantly more mutations compared to multiple myeloma and polyclonal sequences, whereas AL-associated λ light chains had fewer mutations. Machine learning tools designed to predict amyloid propensity were less accurate for new sequences than their original training data.</p><p><strong>Conclusions: </strong>Rarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-10"},"PeriodicalIF":5.2,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis, manifestations, diagnosis, and management of CNS complications in hereditary ATTR amyloidosis.","authors":"Yoshiki Sekijima, Luísa Sousa","doi":"10.1080/13506129.2024.2435573","DOIUrl":"10.1080/13506129.2024.2435573","url":null,"abstract":"<p><p>The clinical efficacy of transthyretin (TTR) tetramer stabilisers and <i>TTR</i> gene silencers in addition to liver transplantation has been established for hereditary ATTR (ATTRv) amyloidosis. Accordingly, non-central nervous system (CNS) systemic amyloidosis manifestations, such as peripheral neuropathy and cardiomyopathy, are now being overcome. However, emerging disease-modifying therapeutics have limited effects on CNS amyloidosis since they target the blood-circulating TTR produced in the liver, and not the cerebral spinal fluid (CSF) TTR synthesised in the choroid plexus. CNS involvement is therefore becoming the most common and severe complication in patients with ATTRv amyloidosis, including transient focal neurologic episodes, haemorrhagic and ischaemic stroke, cognitive decline, and cranial nerve dysfunction. Pathologically, extensive amyloid depositions are observable in the leptomeninges and leptomeningeal vessels, which are in direct contact with the CSF. Amyloid positron emission tomography is a useful biomarker for the early detection and treatment evaluation of early-onset ATTRv amyloidosis with the V30M (p.V50M) variant. Treatment-wise, blood-brain barrier-permeable stabilisers, intrathecal injection of silencers, and monoclonal antibodies against misfolded TTR and/or ATTR amyloid may potentially ameliorate CNS ATTR amyloidosis. The development of novel imaging/CSF biomarkers and disease-modifying therapies are the greatest unmet medical need in ATTRv amyloidosis and require further clinical trials.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-12"},"PeriodicalIF":5.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.","authors":"Tsai-Jou Su, Chien-Ho Janice Lin, Yen-Lin Liu, Hsueh-Wen Hsueh, Sung-Tsang Hsieh, Chi-Chao Chao, Ming-Chang Chiang","doi":"10.1080/13506129.2024.2383450","DOIUrl":"10.1080/13506129.2024.2383450","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN.</p><p><strong>Methods: </strong>Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed.</p><p><strong>Results: </strong>Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability.</p><p><strong>Conclusions: </strong>Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"257-265"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and predictors of sudden death in patients with cardiac amyloidosis.","authors":"Fernando de Frutos, Giulia Saturi, Esther Gonzalez-Lopez, Maurizio Sguazzotti, Fernando Dominguez, Alberto Ponziani, Eva Cabrera-Romero, Angelo Giuseppe Caponetti, Sara Lozano, Paolo Massa, Belen Peiro-Aventin, Antonella Accietto, Nerea Mora-Ayestarán, Alessandro Giovannetti, Victor Castro-Urda, Christian Gagliardi, Marta Cobo-Marcos, Rafael Rios-Tamayo, Elena Biagini, Manuel Gomez-Bueno, Nazzareno Galiè, Javier Segovia-Cubero, Simone Longhi, Pablo Garcia-Pavia","doi":"10.1080/13506129.2024.2414295","DOIUrl":"10.1080/13506129.2024.2414295","url":null,"abstract":"<p><strong>Introduction: </strong>Although sudden death (SD) is a recognized complication of cardiac amyloidosis, there is scarce data about its incidence, mechanisms, and predictors. The aim of this study was to describe incidence of SD and to analyze possible risk factors.</p><p><strong>Methods: </strong>Consecutive patients with ATTR or AL cardiac amyloidosis evaluated at two European centers were identified. SD was defined as unexpected death in clinically stable patients. Cox proportional hazard regression was performed to assess risk factors in univariate analysis. Those statistically significant were then assessed through age-adjusted multivariate analysis.</p><p><strong>Results: </strong>Analysis included 784 patients, 569 with ATTR amyloidosis (mean age 74.1 ± 12.1 years) and 215 with AL amyloidosis (mean age 64.5 ± 10.8 years). After a median follow-up of 1.9 years, SD rate at 2 years was 1.8% in ATTR. Previous pacemaker implantation (PPM) was associated with increased risk after age-adjusted analysis (HR 4.97; 95%CI: 1.39-17.7; <i>p</i> = 0.01). SD rate in AL amyloidosis patients at 2 years was 8.0% after a median follow-up of 1.2 years. Betablockers and NYHA III-IV were independently associated with an increased risk after age-adjusted multivariate analysis (HR 7.06 95%CI (2.31-21.5) <i>p</i> = 0.001) and (HR 4.56 95%CI (1.51-13.8) <i>p</i> = 0.007) respectively.</p><p><strong>Conclusions: </strong>SD is more frequent in AL than in ATTR cardiac amyloidosis. SD is associated with different risk factors in both entities.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"334-338"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}