Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis.","authors":"Maria Ungericht, Valeria Groaz, Moritz Messner, Thomas Schuetz, Luca Brunelli, Marc-Michael Zaruba, Daniela Lener, Eva Stocker, Axel Bauer, Alexander Stephan Kroiss, Agnes Mayr, Christoph Röcken, Gerhard Poelzl","doi":"10.1080/13506129.2023.2239986","DOIUrl":"10.1080/13506129.2023.2239986","url":null,"abstract":"<p><strong>Background: </strong>The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB).</p><p><strong>Methods: </strong>Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods.</p><p><strong>Results: </strong>Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score (<i>r</i> = 0.69, <i>p</i> < .001) as well as with cardiac 99mTc-DPD uptake (planar: <i>r</i> = 0.64, <i>p</i> < .001; H/WB: <i>r</i> = 0.50, <i>p</i> = .014; SPECT/CT: <i>r</i> = 0.53, <i>p</i> = .008; H/CL: <i>r</i> = 0.43, <i>p</i> = .037) (results are shown for correlations with Congo Red-staining).</p><p><strong>Conclusion: </strong>In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"22-31"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9917681","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":"Heterogeneous worldwide access and pricing of Tafamidis.","authors":"Abdirahman Wardhere, Dimitrios Bampatsias, Nowell Fine, Pablo Garcia-Pavia, Martha Grogan, Arnt V Kristen, Thibaud Damy, Yoshiki Sekijima, Mathew S Maurer","doi":"10.1080/13506129.2023.2263620","DOIUrl":"10.1080/13506129.2023.2263620","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"73-75"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167104","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":"Diagnostic and prognostic contribution of DPD scintigraphy in transthyretin V30M cardiac amyloidosis.","authors":"Maria C Azevedo Coutinho, Nuno Cortez-Dias, Guilhermina Cantinho, Susana Gonçalves, Nelson Cunha, Tiago Rodrigues, Laura Santos, Isabel Conceição, João Agostinho, Fausto J Pinto","doi":"10.1080/13506129.2023.2239987","DOIUrl":"10.1080/13506129.2023.2239987","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis and prognostic stratification of cardiac transthyretin amyloidosis are crucial. Although ^99mTc 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy is the preferred method for the non-invasive diagnosis, its accuracy appears to be limited in transthyretin amyloidosis protein (ATTR) V30M mutation. Furthermore, its prognostic value in this mutation is unknown. This study investigated the diagnostic value of DPD scintigraphy to detect ATTR cardiomyopathy in V30M mutation and explored its prognostic value regarding mortality.</p><p><strong>Methods: </strong>A total of 288 ATTR V30M mutation carriers (median age: 46 years; 49% males) without myocardial thickening (defined as septal thickness ≥13mm) attributable to other causes and who underwent DPD scintigraphy were enrolled. ATTR cardiomyopathy was defined by septal thickness ≥13mm and at least one of the criteria: late heart-to-mediastinum (H/M) ¹²³I-metaiodobenzylguanidine (MIBG) uptake ratio <1.60; electrical heart disease or biopsy-documented amyloidosis.</p><p><strong>Results: </strong>ATTR cardiomyopathy was identified in 41 (14.2%) patients and cardiac DPD uptake in 34 (11.8%). During a mean follow-up of 33.6 ± 1.2 months, 16 patients died (5.6%). Mortality was 14 times higher in patients with ATTR cardiomyopathy, 13 times higher in those with DPD uptake and 10 times higher in those with late H/M MIBG <1.60. The combined assessment of septal thickness and cardiac DPD uptake improved risk stratification: patients without septal thickening and without DPD retention had an excellent prognosis while those who presented either or both of them had a significantly worse prognosis, with 5-year mortality rates ranging from 39.9 to 53.3%.</p><p><strong>Conclusions: </strong>DPD scintigraphy is useful for prognostic stratification of ATTR V30M mutation carriers. Patients without septal thickening and no DPD uptake present the best prognosis compared to those with any signs of cardiac involvement.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"32-41"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868164","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":"Inappropriate use of technetium-99m pyrophosphate scanning for the evaluation of transthyretin amyloidosis.","authors":"Crystal Lihong Yan, Nina Thakkar Rivera, James Hoffman","doi":"10.1080/13506129.2023.2267162","DOIUrl":"10.1080/13506129.2023.2267162","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"76-78"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163161","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":"AA amyloidosis in a father and daughter as complication of <i>PSTPIP1</i>-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.","authors":"Anne F Brunger, Hans L A Nienhuis, Johan Bijzet, Evelien Zonneveld-Huijssoon, Jan S F Sanders, Geertje E Legger, Reinold O B Gans, Bouke P C Hazenberg","doi":"10.1080/13506129.2023.2272556","DOIUrl":"10.1080/13506129.2023.2272556","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"82-84"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693691","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":"The way to a man's heart: prostate samples for the early detection of transthyretin cardiomyopathy.","authors":"Lawrence Zeldin, Karan Wats, Kathleen M O'Toole, Fabrizio Remotti, Mathew S Maurer","doi":"10.1080/13506129.2023.2268812","DOIUrl":"10.1080/13506129.2023.2268812","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"79-81"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219511","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":"Treatment response and neurofilament light chain levels with long-term patisiran in hereditary transthyretin-mediated amyloidosis with polyneuropathy: 24-month results of an open-label extension study.","authors":"Simina Ticau, Emre Aldinc, Michael Polydefkis, David Adams, Teresa Coelho, Mitsuharu Ueda, Cecilia Hale, John Vest, Paul Nioi","doi":"10.1080/13506129.2023.2232520","DOIUrl":"10.1080/13506129.2023.2232520","url":null,"abstract":"<p><strong>Background: </strong>Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy.</p><p><strong>Methods: </strong>All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.</p><p><strong>Results: </strong>Patients receiving patisiran in the parent study (APOLLO-patisiran, <i>n</i> = 137; phase II OLE-patisiran, <i>n</i> = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran -4.8 (-8.9, -0.6); phase II OLE-patisiran -5.8 (-10.5, -1.2)) and Norfolk QOL-DN (APOLLO-patisiran -2.4 (-7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (<i>n</i> = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.</p><p><strong>Conclusions: </strong>Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"1-11"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962009","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":"Patient-reported outcome measures for transthyretin cardiac amyloidosis: the ITALY study.","authors":"Alberto Aimo, Lucio Teresi, Vincenzo Castiglione, Anna Lisa Picerni, Martina Niccolai, Silvia Severino, Assunta Agazio, Anna Carnevale Baraglia, Laura Obici, Giovanni Palladini, Lucia Ponti, Alessia Argirò, Francesco Cappelli, Federico Perfetto, Matteo Serenelli, Giancarlo Trimarchi, Roberto Licordari, Gianluca Di Bella, Olena Chubuchna, Filippo Quattrone, Sabina Nuti, Sabina De Rosis, Claudio Passino, Claudio Rapezzi, Giampaolo Merlini, Michele Emdin, Giuseppe Vergaro","doi":"10.1080/13506129.2023.2254451","DOIUrl":"10.1080/13506129.2023.2254451","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin cardiac amyloidosis (ATTR-CA) has a deep impact on the quality of life (QoL), yet no specific patient-reported outcome measures (PROMs) for ATTR-CA exist.</p><p><strong>Methods: </strong>The ITALY study involved 5 Italian referral centres (Pisa, Pavia, Ferrara, Florence, Messina) enrolling consecutive outpatients with ATTR-CA.</p><p><strong>Results: </strong>Two 30-item questionnaires were created for wild-type (wt) and variant (v) ATTR-CA. Scores ranged from 100 (best condition) to 0 (worst condition). Out of 140 patients enrolled (77% with ATTRwt-CA), 115 repeated the re-evaluation at 6 months. At baseline, only 30% of patients needed help to fill out the questionnaires. Among baseline variables, all KCCQ and SF-36 domains were univariate predictors of ITALY scores in ATTRwt-CA patients, with the KCCQ Symptom Summary score (beta coefficient 0.759), Social Limitations (0.781), and Overall summary score (0.786) being the strongest predictors. The SF-36 Emotional well-being score (0.608), the KCCQ Overall summary score (0.656), and the SF-36 Energy/fatigue score (0.669) were the strongest univariate predictors of ITALY scores in ATTRv-CA. Similar results were found at 6 months.</p><p><strong>Conclusions: </strong>The ITALY questionnaires are the first specific PROMs for ATTRwt- and ATTRv-CA. Questionnaire completion is feasible. ITALY scores display close relationships with non-ATTR-specific measures of QoL.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"52-61"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155815","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":"Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.","authors":"Guillaume Fargeot, Andoni Echaniz-Laguna, Céline Labeyrie, Juliette Svahn, Jean-Philippe Camdessanché, Pascal Cintas, Jean-Baptiste Chanson, Florence Esselin, Céline Piedvache, Céline Verstuyft, Steeve Genestet, Emmeline Lagrange, Laurent Magy, Yann Péréon, Sabrina Sacconi, Aissatou Signate, Aleksandra Nadaj-Pakleza, Frédéric Taithe, Karine Viala, Céline Tard, Vianney Poinsignon, Cécile Cauquil, Shahram Attarian, David Adams","doi":"10.1080/13506129.2023.2270661","DOIUrl":"10.1080/13506129.2023.2270661","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from <i>TTR</i> gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available.</p><p><strong>Methods: </strong>In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the <i>TTR</i> gene in French patients with age >50 years with a progressive idiopathic polyneuropathy.</p><p><strong>Results: </strong>553 patients (70% males) with a mean age of 70 years were included. A <i>TTR</i> gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met <i>TTR</i> variation in 10 cases. In comparison with patients with no <i>TTR</i> gene pathogenic variants (<i>n</i> = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, <i>p</i> = .007), significant weight loss (33 vs 11%, <i>p</i> = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, <i>p</i> = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives.</p><p><strong>Conclusion: </strong>In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"62-69"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684662","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":"Reduction in ^99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.","authors":"René Rettl, Raffaella Calabretta, Franz Duca, Christina Binder, Christina Kronberger, Robin Willixhofer, Michael Poledniczek, Carolina Donà, Christian Nitsche, Dietrich Beitzke, Christian Loewe, Michaela Auer-Grumbach, Diana Bonderman, Stefan Kastl, Christian Hengstenberg, Roza Badr Eslam, Johannes Kastner, Jutta Bergler-Klein, Marcus Hacker, Andreas Kammerlander","doi":"10.1080/13506129.2023.2247136","DOIUrl":"10.1080/13506129.2023.2247136","url":null,"abstract":"<p><p><b>Aims:</b> Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.<b>Methods and results:</b> ATTRv-CM patients underwent [^99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: <i>n</i> = 5, inotersen: <i>n</i> = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, <i>p</i> = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, <i>p</i> < .001) in ATTRwt-CM patients (historical control cohort: <i>n</i> = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.<b>Conclusions:</b> RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial ^99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"42-51"},"PeriodicalIF":5.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10088979","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}