Pub Date : 2023-12-01Epub Date: 2023-05-15DOI: 10.1080/13506129.2023.2212394
J C Purrucker, C Röcken, D Reuss
{"title":"Iatrogenic cerebral amyloid angiopathy rather than sporadic CAA in younger adults with lobar intracerebral haemorrhage.","authors":"J C Purrucker, C Röcken, D Reuss","doi":"10.1080/13506129.2023.2212394","DOIUrl":"10.1080/13506129.2023.2212394","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816463","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}
Pub Date : 2023-12-01Epub Date: 2023-06-23DOI: 10.1080/13506129.2023.2226298
Christian Treitz, Neelis Müller-Marienburg, Rolf Rüdiger Meliß, Peter Urban, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Klaus Martens, Hans-Michael Behrens, Eva Gericke, Andreas Tholey, Christoph Röcken
Introduction: Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.
Methods: 205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.
Results: Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.
Conclusion: Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.
{"title":"ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger.","authors":"Christian Treitz, Neelis Müller-Marienburg, Rolf Rüdiger Meliß, Peter Urban, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Klaus Martens, Hans-Michael Behrens, Eva Gericke, Andreas Tholey, Christoph Röcken","doi":"10.1080/13506129.2023.2226298","DOIUrl":"10.1080/13506129.2023.2226298","url":null,"abstract":"<p><strong>Introduction: </strong>Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.</p><p><strong>Methods: </strong>205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.</p><p><strong>Results: </strong>Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.</p><p><strong>Conclusion: </strong>Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678601","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}
Pub Date : 2023-12-01Epub Date: 2023-07-11DOI: 10.1080/13506129.2023.2230516
Francesco Marchi, Chiara Kessler, Daniela Distefano, Lodovico Terzi di Bergamo, Luca Fumagalli, Manuela Averaimo, Emanuele Crupi, Fabio Bergamini, Giorgia Melli, Georg Stussi, Davide Rossi, Claudio Gobbi, Paolo Ripellino, Emanuele Pravatà, Dominique E Kuhlen, Christoph Röcken, Pietro Scarone, Bernhard Gerber, Adalgisa Condoluci
Background: Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS.
Methods: Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC).
Results: Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (p < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, p = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed.
Conclusions: Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.
背景:转甲状腺素(ATTR)淀粉样变通常在发生不可逆心脏损伤的晚期诊断出来。腰椎管狭窄(LSS)可能早于心脏ATTR淀粉样变多年,这为在LSS手术时检测ATTR提供了机会。我们通过组织活检前瞻性地评估了年龄>50岁的LSS手术患者黄韧带ATTR的患病率。方法:术前采用轴向T2磁共振成像(MRI)片评估黄韧带厚度。采用刚果红染色和免疫组化(IHC)对黄韧带组织样本进行集中筛选。结果:94例患者中有74例(78.7%)检出黄韧带淀粉样蛋白。61例(64.9%)IHC显示ATTR, 13例(13.8%)淀粉样蛋白分型不确定。淀粉样蛋白患者黄韧带的平均厚度在所有水平上均显著增高(p p = 0.01)。性别、合并症、既往腕管综合征或LSS手术均无差异。结论:淀粉样蛋白主要为ATTR亚型,在5例LSS患者中发现4例,并与年龄和黄韧带厚度相关。黄韧带的组织病理学检查可能为未来的决策提供信息。
{"title":"Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis.","authors":"Francesco Marchi, Chiara Kessler, Daniela Distefano, Lodovico Terzi di Bergamo, Luca Fumagalli, Manuela Averaimo, Emanuele Crupi, Fabio Bergamini, Giorgia Melli, Georg Stussi, Davide Rossi, Claudio Gobbi, Paolo Ripellino, Emanuele Pravatà, Dominique E Kuhlen, Christoph Röcken, Pietro Scarone, Bernhard Gerber, Adalgisa Condoluci","doi":"10.1080/13506129.2023.2230516","DOIUrl":"10.1080/13506129.2023.2230516","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS.</p><p><strong>Methods: </strong>Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (<i>p</i> < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, <i>p</i> = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed.</p><p><strong>Conclusions: </strong>Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769792","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}
Pub Date : 2023-12-01Epub Date: 2023-07-14DOI: 10.1080/13506129.2023.2226299
Bengt Zöller, Eric Manderstedt, Christina Lind-Halldén, Christer Halldén
{"title":"Rare-variant collapsing and bioinformatic analyses for amyloidosis, dementia and Parkinson's disease in the UK biobank reveal novel susceptibility loci.","authors":"Bengt Zöller, Eric Manderstedt, Christina Lind-Halldén, Christer Halldén","doi":"10.1080/13506129.2023.2226299","DOIUrl":"10.1080/13506129.2023.2226299","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9781141","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}
Pub Date : 2023-12-01Epub Date: 2023-05-22DOI: 10.1080/13506129.2023.2212397
Elena S Klimtchuk, Daniele Peterle, Esther Bullitt, Lawreen H Connors, John R Engen, Olga Gursky
Background: Immunoglobulin light chain (LC) amyloidosis is a life-threatening disease complicated by vast numbers of patient-specific mutations. We explored 14 patient-derived and engineered proteins related to κ1-family germline genes IGKVLD-33*01 and IGKVLD-39*01.
Methods: Hydrogen-deuterium exchange mass spectrometry analysis of conformational dynamics in recombinant LCs and their fragments was integrated with studies of thermal stability, proteolytic susceptibility, amyloid formation and amyloidogenic sequence propensity. The results were mapped on the structures of native and fibrillary proteins.
Results: Proteins from two κ1 subfamilies showed unexpected differences. Compared to their germline counterparts, amyloid LC related to IGKVLD-33*01 was less stable and formed amyloid faster, whereas amyloid LC related to IGKVLD-39*01 had similar stability and formed amyloid slower, suggesting different major factors influencing amyloidogenesis. In 33*01-related amyloid LC, these factors involved destabilization of the native structure and probable stabilization of amyloid. The atypical behavior of 39*01-related amyloid LC stemmed from increased dynamics/exposure of amyloidogenic segments in βC'V and βEV that could initiate aggregation and decreased dynamics/exposure near the Cys23-Cys88 disulfide.
Conclusions: The results suggest distinct amyloidogenic pathways for closely related LCs and point to the complementarity-defining regions CDR1 and CDR3, linked via the conserved internal disulfide, as key factors in amyloid formation.
{"title":"Role of complementarity-determining regions 1 and 3 in pathologic amyloid formation by human immunoglobulin κ1 light chains.","authors":"Elena S Klimtchuk, Daniele Peterle, Esther Bullitt, Lawreen H Connors, John R Engen, Olga Gursky","doi":"10.1080/13506129.2023.2212397","DOIUrl":"10.1080/13506129.2023.2212397","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin light chain (LC) amyloidosis is a life-threatening disease complicated by vast numbers of patient-specific mutations. We explored 14 patient-derived and engineered proteins related to κ1-family germline genes IGKVLD-33*01 and IGKVLD-39*01.</p><p><strong>Methods: </strong>Hydrogen-deuterium exchange mass spectrometry analysis of conformational dynamics in recombinant LCs and their fragments was integrated with studies of thermal stability, proteolytic susceptibility, amyloid formation and amyloidogenic sequence propensity. The results were mapped on the structures of native and fibrillary proteins.</p><p><strong>Results: </strong>Proteins from two κ1 subfamilies showed unexpected differences. Compared to their germline counterparts, amyloid LC related to IGKVLD-33*01 was less stable and formed amyloid faster, whereas amyloid LC related to IGKVLD-39*01 had similar stability and formed amyloid slower, suggesting different major factors influencing amyloidogenesis. In 33*01-related amyloid LC, these factors involved destabilization of the native structure and probable stabilization of amyloid. The atypical behavior of 39*01-related amyloid LC stemmed from increased dynamics/exposure of amyloidogenic segments in βC'V and βEV that could initiate aggregation and decreased dynamics/exposure near the Cys23-Cys88 disulfide.</p><p><strong>Conclusions: </strong>The results suggest distinct amyloidogenic pathways for closely related LCs and point to the complementarity-defining regions CDR1 and CDR3, linked via the conserved internal disulfide, as key factors in amyloid formation.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9552302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-07-17DOI: 10.1080/13506129.2023.2229484
Teresa Coelho, Angela Dispenzieri, Martha Grogan, Isabel Conceição, Márcia Waddington-Cruz, Arnt V Kristen, Jonas Wixner, Igor Diemberger, Juan Gonzalez-Moreno, Mathew S Maurer, Violaine Planté-Bordeneuve, Pablo Garcia-Pavia, Ivailo Tournev, Jose Gonzalez-Costello, Eve Cariou, Alejandra González-Duarte, Oliver Glass, Doug Chapman, Leslie Amass
{"title":"Patients with transthyretin amyloidosis enrolled in THAOS between 2018 and 2021 continue to experience substantial diagnostic delay.","authors":"Teresa Coelho, Angela Dispenzieri, Martha Grogan, Isabel Conceição, Márcia Waddington-Cruz, Arnt V Kristen, Jonas Wixner, Igor Diemberger, Juan Gonzalez-Moreno, Mathew S Maurer, Violaine Planté-Bordeneuve, Pablo Garcia-Pavia, Ivailo Tournev, Jose Gonzalez-Costello, Eve Cariou, Alejandra González-Duarte, Oliver Glass, Doug Chapman, Leslie Amass","doi":"10.1080/13506129.2023.2229484","DOIUrl":"10.1080/13506129.2023.2229484","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882057","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}
Pub Date : 2023-12-01Epub Date: 2023-07-11DOI: 10.1080/13506129.2023.2232516
Bharadwaj Satyavolu, Genise Green, Anthony Jake Demetris, Prem Soman
{"title":"A rare occurrence and near miss! Should a TTR gene test be routinely performed for suspected ATTR-cardiomyopathy?","authors":"Bharadwaj Satyavolu, Genise Green, Anthony Jake Demetris, Prem Soman","doi":"10.1080/13506129.2023.2232516","DOIUrl":"10.1080/13506129.2023.2232516","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9757535","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}
Pub Date : 2023-12-01Epub Date: 2023-07-13DOI: 10.1080/13506129.2023.2224494
Sabrina Ghosh, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Devin Kenney, Carly S Golden, Camille V Edwards, Vaishali Sanchorawala, Lawreen H Connors, Richard M Giadone, George J Murphy
Background: In ATTR amyloidosis, transthyretin (TTR) protein is secreted from the liver and deposited as toxic aggregates at downstream target tissues. Despite recent advancements in treatments for ATTR amyloidosis, the mechanisms underlying misfolded TTR-mediated cellular damage remain elusive.
Methods: In an effort to define early events of TTR-associated stress, we exposed neuronal (SH-SY5Y) and cardiac (AC16) cells to wild-type and destabilized TTR variants (TTRV122I (p.V142I) and TTRL55P (p.L70P)) and performed transcriptional (RNAseq) and epigenetic (ATACseq) profiling. We subsequently compared TTR-responsive signatures to cells exposed to destabilized antibody light chain protein associated with AL amyloidosis as well as ER stressors (thapsigargin, heat shock).
Results: In doing so, we observed overlapping, yet distinct cell type- and amyloidogenic protein-specific signatures, suggesting unique responses to each amyloidogenic variant. Moreover, we identified chromatin level changes in AC16 cells exposed to mutant TTR that resolved upon pre-incubation with kinetic stabilizer tafamidis.
Conclusions: Collectively, these data provide insight into the mechanisms underlying destabilized protein-mediated cellular damage and provide a robust resource representing cellular responses to aggregation-prone proteins and ER stress.
{"title":"Mapping cellular response to destabilized transthyretin reveals cell- and amyloidogenic protein-specific signatures.","authors":"Sabrina Ghosh, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Devin Kenney, Carly S Golden, Camille V Edwards, Vaishali Sanchorawala, Lawreen H Connors, Richard M Giadone, George J Murphy","doi":"10.1080/13506129.2023.2224494","DOIUrl":"10.1080/13506129.2023.2224494","url":null,"abstract":"<p><strong>Background: </strong>In ATTR amyloidosis, transthyretin (TTR) protein is secreted from the liver and deposited as toxic aggregates at downstream target tissues. Despite recent advancements in treatments for ATTR amyloidosis, the mechanisms underlying misfolded TTR-mediated cellular damage remain elusive.</p><p><strong>Methods: </strong>In an effort to define early events of TTR-associated stress, we exposed neuronal (SH-SY5Y) and cardiac (AC16) cells to wild-type and destabilized TTR variants (TTR<sup>V122I</sup> (p.V142I) and TTR<sup>L55P</sup> (p.L70P)) and performed transcriptional (RNAseq) and epigenetic (ATACseq) profiling. We subsequently compared TTR-responsive signatures to cells exposed to destabilized antibody light chain protein associated with AL amyloidosis as well as ER stressors (thapsigargin, heat shock).</p><p><strong>Results: </strong>In doing so, we observed overlapping, yet distinct cell type- and amyloidogenic protein-specific signatures, suggesting unique responses to each amyloidogenic variant. Moreover, we identified chromatin level changes in AC16 cells exposed to mutant TTR that resolved upon pre-incubation with kinetic stabilizer tafamidis.</p><p><strong>Conclusions: </strong>Collectively, these data provide insight into the mechanisms underlying destabilized protein-mediated cellular damage and provide a robust resource representing cellular responses to aggregation-prone proteins and ER stress.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9985612","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}
Pub Date : 2023-12-01Epub Date: 2023-06-23DOI: 10.1080/13506129.2023.2226295
Catarina Falcão de Campos, Isabel Conceição
{"title":"Neuropathy progression in hereditary transthyretin amyloidosis (ATTRv) patients after liver transplantation.","authors":"Catarina Falcão de Campos, Isabel Conceição","doi":"10.1080/13506129.2023.2226295","DOIUrl":"10.1080/13506129.2023.2226295","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670809","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}
Pub Date : 2023-09-01DOI: 10.1080/13506129.2022.2164488
Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, Morie Gertz, Ashutosh Wechalekar, Giovanni Palladini, Raymond Comenzo, Rafael Fonseca, Arnaud Jaccard, Efstathios Kastritis, Stefan Schönland, Charles la Porte, Huiling Pei, NamPhuong Tran, Giampaolo Merlini
Background: Cytogenetic abnormalities are common in patients with amyloid light-chain (AL) amyloidosis; some are associated with poorer outcomes. This post hoc analysis of ANDROMEDA evaluated the impact of certain cytogenetic abnormalities on outcomes in this patient population.
Methods: Patients with newly diagnosed AL amyloidosis were randomised 1:1 to daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) or VCd. Outcomes were evaluated in the intent-to-treat (ITT) population and in patients with t(11;14), amp1q21, del13q14, and del17p13.
Results: Overall, 321 patients had cytogenetic testing (D-VCd, n = 155; VCd, n = 166); most common abnormalities were t(11;14) and amp1q21. At a median follow-up of 20.3 months, haematologic complete response rates were higher with D-VCd vs VCd across all cytogenetic subgroups and organ response rates were numerically higher with D-VCd vs VCd across most subgroups. Point estimates for hazard ratio of major organ deterioration-PFS and -EFS favoured D-VCd over VCd for all cytogenetic subgroups. Deep haematologic responses (involved minus uninvolved free light chains [FLC] <10 mg/L or involved FLC ≤20 mg/L) were seen in more patients with D-VCd than VCd in all ITT and t(11;14) cohorts.
Conclusions: These results support the use of D-VCd as standard of care in patients with newly diagnosed AL amyloidosis regardless of cytogenetic abnormalities.
背景:细胞遗传学异常在淀粉样蛋白轻链(AL)淀粉样变性患者中很常见;有些与较差的结果有关。这个事后分析的ANDROMEDA评估了某些细胞遗传学异常对该患者群体结果的影响。方法:新诊断的AL淀粉样变性患者按1:1随机分配至达拉单抗、硼替佐米、环磷酰胺和地塞米松组(D-VCd)或VCd组。在意向治疗(ITT)人群和t(11;14)、amp1q21、del13q14和del17p13患者中评估结果。结果:321例患者进行了细胞遗传学检测(D-VCd, n = 155;VCd, n = 166);最常见的异常是t(11;14)和amp1q21。在20.3个月的中位随访中,在所有细胞遗传学亚组中,D-VCd与VCd的血液学完全缓解率更高,在大多数亚组中,D-VCd与VCd的器官反应率在数值上更高。主要器官恶化的风险比- pfs和-EFS的点估计在所有细胞遗传学亚组中都倾向于D-VCd而不是VCd。结论:这些结果支持将D-VCd作为新诊断的AL淀粉样变性患者的标准治疗,无论细胞遗传学异常如何。
{"title":"Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study.","authors":"Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, Morie Gertz, Ashutosh Wechalekar, Giovanni Palladini, Raymond Comenzo, Rafael Fonseca, Arnaud Jaccard, Efstathios Kastritis, Stefan Schönland, Charles la Porte, Huiling Pei, NamPhuong Tran, Giampaolo Merlini","doi":"10.1080/13506129.2022.2164488","DOIUrl":"https://doi.org/10.1080/13506129.2022.2164488","url":null,"abstract":"<p><strong>Background: </strong>Cytogenetic abnormalities are common in patients with amyloid light-chain (AL) amyloidosis; some are associated with poorer outcomes. This post hoc analysis of ANDROMEDA evaluated the impact of certain cytogenetic abnormalities on outcomes in this patient population.</p><p><strong>Methods: </strong>Patients with newly diagnosed AL amyloidosis were randomised 1:1 to daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) or VCd. Outcomes were evaluated in the intent-to-treat (ITT) population and in patients with t(11;14), amp1q21, del13q14, and del17p13.</p><p><strong>Results: </strong>Overall, 321 patients had cytogenetic testing (D-VCd, <i>n</i> = 155; VCd, <i>n</i> = 166); most common abnormalities were t(11;14) and amp1q21. At a median follow-up of 20.3 months, haematologic complete response rates were higher with D-VCd vs VCd across all cytogenetic subgroups and organ response rates were numerically higher with D-VCd vs VCd across most subgroups. Point estimates for hazard ratio of major organ deterioration-PFS and -EFS favoured D-VCd over VCd for all cytogenetic subgroups. Deep haematologic responses (involved minus uninvolved free light chains [FLC] <10 mg/L or involved FLC ≤20 mg/L) were seen in more patients with D-VCd than VCd in all ITT and t(11;14) cohorts.</p><p><strong>Conclusions: </strong>These results support the use of D-VCd as standard of care in patients with newly diagnosed AL amyloidosis regardless of cytogenetic abnormalities.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10100063","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}