Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Cardiac amyloidosis remains significantly underdiagnosed in patients undergoing TAVR: analysis of National Inpatient Sample.","authors":"Dimitrios Terentes-Printzios, Alexios S Antonopoulos, Mohamed Omer, Ioannis Panagiotopoulos, Konstantinos Toutouzas, Konstantinos Tsioufis, Islam Elgendy, Charalambos Vlachopoulos","doi":"10.1080/13506129.2022.2159369","DOIUrl":"https://doi.org/10.1080/13506129.2022.2159369","url":null,"abstract":"Transthyretin cardiomyopathy (ATTR-CM) is among the causes of heart failure with the gravest prognosis. It is estimated that approximately one in four patients with ATTRCM die within 2 years from diagnosis [1]. Recent studies [2,3] have demonstrated that the prevalence of cardiac amyloidosis, mainly wild type ATTR-CM, is as high as 15% in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). In a meta-analysis of all published evidence, we have recently shown that the pooled estimates for the prevalence of cardiac amyloidosis in TAVR is 11.2%, 95% confidence intervals (CI) 9.4–13.3% [1]. Whilst awareness for this condition is increasing, there are still concerns that ATTR-CM remains underdiagnosed and undertreated [4]. In the present study, we sought to explore the prevalence of cardiac amyloidosis cases among patients undergoing TAVR in the United States (U.S). We used data from the U.S. National Inpatient Sample (NIS) from October 2015 to the end of 2019 (Figure 1(A)) [5]. First, we identified hospital admissions with performed TAVR operations using the following ICD-10-PCS Procedure Codes: ‘02RF37H’, ‘02RF38H’, ‘02RF3J’, ‘02RF3KH’, ‘02RF37Z’, ‘02RF38Z’, ‘02RF3JZ’, ‘02RF3KZ’). Then we searched for all hospitalisations with a diagnosis of amyloidosis based on the ICD-10-CM codes (E850, E851, E852, E853, E854, E858, E8582, E8589, E859). In total we identified n1⁄4 45,660 hospital admissions that underwent a TAVR procedure. Extrapolating evidence from our recent meta-analysis on the estimates for cardiac amyloidosis in TAVR, we estimated that the incident amyloidosis cases in this population would be expected to be 5114 cases (95%CI: between 4292 and 6073). However, in the NIS data sample only n1⁄4 47 hospitalised TAVR cases had an ICD-10-CM code relevant to amyloidosis (Figure 1(B)). This accounts for only 1% of the expected patient sample with concomitant severe aortic stenosis undergoing TAVR and potentially latent amyloidosis (n1⁄4 5114). Patients with amyloidosis were less likely to be females, with a non-significant trend for being younger, undergoing non-elective TAVR procedure, having a longer length of in-hospital stay and higher hospitalisation costs (Figure 1(C)) compared to TAVR cases without concomitant amyloidosis; there were no significant differences in the need for permanent pacemaker implantation. Importantly, in-hospital mortality rates were higher in CA amyloidosis patients (4.3% vs. 1.4%, adjusted p1⁄4 0.086, Figure 1(D)). The NIS approximates a 20% stratified sample of discharges from U.S. community hospitals. Extrapolation of the NIS data to all U.S hospitalisations, would yield a statistically significant association between amyloidosis and TAVR in-hospital mortality (unadjusted OR 1⁄4 3.04, 95%CI 1.610–5.73, p< 0.001, and adjusted OR 2.84, 95%CI 1.50–5.38, p< 0.001 after adjustment for age, sex, and nonelective status of the procedure, Figure 1(E)). According to these findings only ","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"246-247"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9783775","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":"Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain.","authors":"Fernando de Frutos,&nbsp;Juan Pablo Ochoa,&nbsp;Cristina Gómez-González,&nbsp;David Reyes-Leiva,&nbsp;Juan I Aróstegui,&nbsp;Carlos Casasnovas,&nbsp;Roberto Barriales-Villa,&nbsp;Teresa Sevilla,&nbsp;Esther Gonzalez-Lopez,&nbsp;Elvira Ramil,&nbsp;Lucia Galan,&nbsp;Jose González-Costello,&nbsp;Ana García-Álvarez,&nbsp;Ricard Rojas-Garcia,&nbsp;Maria Angeles Espinosa,&nbsp;Pablo Garcia-Pavia","doi":"10.1080/13506129.2022.2142110","DOIUrl":"https://doi.org/10.1080/13506129.2022.2142110","url":null,"abstract":"<p><strong>Background: </strong>The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain.</p><p><strong>Methods: </strong>Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals.</p><p><strong>Results: </strong>Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7-9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis (<i>p</i> < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain.</p><p><strong>Conclusions: </strong>Glu89Lys ATTRv is a <i>TTR</i> variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"199-207"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161675","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":"Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis.","authors":"Hiroki Miyahara,&nbsp;Jian Dai,&nbsp;Ying Li,&nbsp;Xiaoran Cui,&nbsp;Hibiki Takeuchi,&nbsp;Naomi Hachiya,&nbsp;Fuyuki Kametani,&nbsp;Masahide Yazaki,&nbsp;Masayuki Mori,&nbsp;Keiichi Higuchi","doi":"10.1080/13506129.2022.2153667","DOIUrl":"https://doi.org/10.1080/13506129.2022.2153667","url":null,"abstract":"<p><p>Amyloidosis refers to a group of degenerative diseases that are characterized by the deposition of misfolded protein fibrils in various organs. Deposited amyloid may be removed by a phagocyte-dependent innate immune system; however, the precise mechanisms during disease progression remain unclear. We herein investigated the properties of macrophages that contribute to amyloid degradation and disease progression using inducible apolipoprotein A-II amyloidosis model mice. Intravenously injected AApoAII amyloid was efficiently engulfed by reticuloendothelial macrophages in the liver and spleen and disappeared by 24 h. While cultured murine macrophages degraded AApoAII <i>via</i> the endosomal-lysosomal pathway, AApoAII fibrils reduced cell viability and phagocytic capacity. Furthermore, the depletion of reticuloendothelial macrophages before the induction of AApoAII markedly increased hepatic and splenic AApoAII deposition. These results highlight the physiological role of reticuloendothelial macrophages in the early stages of pathogenesis and suggest the maintenance of phagocytic integrity as a therapeutic strategy to inhibit disease progression.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"225-238"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144784","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":"Pulmonary function tests reveal unrecognised lung dysfunction and have independent prognostic significance in patients with systemic AL amyloidosis.","authors":"Georgia Trakada,&nbsp;Despina Fotiou,&nbsp;Anastasios Kallianos,&nbsp;Foteini Theodorakakou,&nbsp;Magdalini Migkou,&nbsp;Maria Gavriatopoulou,&nbsp;Nikolaos Kanellias,&nbsp;Panagiotis Malandrakis,&nbsp;Ioannis Ntanasis-Stathopoulos,&nbsp;Evangelos Eleutherakis-Papaiakovou,&nbsp;Ioanna Dialoupi,&nbsp;Evangelos Terpos,&nbsp;Meletios A Dimopoulos,&nbsp;Efstathios Kastritis","doi":"10.1080/13506129.2022.2136519","DOIUrl":"https://doi.org/10.1080/13506129.2022.2136519","url":null,"abstract":"<p><strong>Background: </strong>Lung involvement in AL amyloidosis is not very common, but post-mortem data and retrospective studies suggest it is likely underrecognized.</p><p><strong>Aim: </strong>To perform a comprehensive evaluation of lung function with pulmonary function tests (PFTs) in patients with newly diagnosed AL amyloidosis.</p><p><strong>Methods: </strong>A prospective, non-interventional study of 139 consecutive patients with newly diagnosed AL amyloidosis.</p><p><strong>Results: </strong>PFTs indicated normal breathing physiology in 68% of patients, obstructive in 9% and restrictive in 23%; the latter was associated with worse survival (28.6 vs 76 months for obstructive/normal physiology, <i>p</i> = 0.002) and remained significant after adjustment for Mayo stage and abnormal chest-CT. Forced vital capacity <80% of predicted value, forced expiratory volume <80% of predicted value, and carbon monoxide diffusion capacity <70% were independently associated with poorer survival. Respiratory muscle strength (as assessed by maximal expiratory (Pe) and inspiratory (Pi) pressure) was affected in most patients (64% had Pi < 55% and 57% had Pe < 70% of predicted values). Pe% was an independent prognostic factor for survival (HR: 0.984 per 1% unit increase, <i>p</i> = 0.007).</p><p><strong>Conclusions: </strong>Pulmonary dysfunction, as assessed with PFTs, is common and underrecognized in patients with systemic AL amyloidosis, with significant prognostic and potentially therapeutic implications, independent of the degree of cardiac dysfunction or chest-CT findings.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"153-160"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785342","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":"A second case of liraglutide-type localised amyloidosis.","authors":"Sara Muhammad,&nbsp;Ellen D McPhail,&nbsp;W Oliver Tobin,&nbsp;Surendra Dasari,&nbsp;Jason Theis,&nbsp;Julie A Vrana,&nbsp;Elie Naddaf","doi":"10.1080/13506129.2022.2151889","DOIUrl":"https://doi.org/10.1080/13506129.2022.2151889","url":null,"abstract":"Amyloidosis is characterised by extracellular deposition of proteinaceous fibrils, disrupting tissue structure and function. There are at least 36 different types of amyloid, and correct identification of the specific amyloid precursor protein is of paramount importance, as therapy varies dramatically depending on the amyloid type. The most common amyloid types encountered in peripheral nerves are AL (immunoglobulin light chain) and ATTR (transthyretin) [1]. Iatrogenic amyloidosis is a form of localised amyloidosis, caused by the repetitive injection of protein medications, such as insulin [2]. A 78-year-old male, with a history of well-controlled diabetes mellitus, presented with a 30-year history of bilateral foot soreness and numbness. Six months prior to the presentation, he developed intermittent burning and a hot/cold sensation in his feet which spontaneously improved. He also reported a 15-year history of nonradiating low back pain. He had no weakness, weight loss, orthostatic light-headedness, or bowel or bladder dysfunction. Other family members have reported similar sensory symptoms. Neurological examination was remarkable for decreased pinprick sensation from the mid-shin down to the toes, and mildly decreased hot temperature sensation in the right foot. Reflexes were decreased at the right patella, absent at the left patella and bilateral ankles. Motor and gait examination were normal. Nerve conduction studies/electromyography demonstrated mild bilateral old or chronic L5 radiculopathies with no evidence of ongoing denervation, and no evidence of a large fibre peripheral neuropathy. Thermoregulatory sweat test showed no evidence of a small fibre neuropathy either. However, serologic evaluation, performed to screen for potential peripheral neuropathy causes prior to our evaluation, showed a triclonal gammopathy of uncertain significance (IgG j, IgG k and IgA j). Congo red stain performed on an abdominal fat aspirate was positive for amyloid (Figure 1), raising the possibility of systemic amyloidosis. The patient had TTR sequencing which revealed no mutation. Upon questioning about insulin injections, known to cause focal amyloid deposits, the patient acknowledged using liraglutide 0.6mg subcutaneously once daily. Typing of the amyloid deposit by mass spectrometry-based proteomics (liquid chromatography with tandem mass spectrometry; LC-MS-MS) using previously published methods confirmed the presence of liraglutide-type amyloid deposit (Figure 1) [3]. Immunohistochemical studies were not performed because the specimen was a fat aspirate and hence, paraffin-embedded samples were not available. Liraglutide is an acylated glucagon-like peptide-1 analogue that is administered as a subcutaneous injection for the treatment of type 2 diabetes mellitus. To date, a single case of liraglutide-type amyloidosis has been reported [4]. Liraglutide should be considered as a potential amyloidogenic agent. Our case highlights the importance of","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"244-245"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786739","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":"Relationship of binding-site occupancy, transthyretin stabilisation and disease modification in patients with tafamidis-treated transthyretin amyloid cardiomyopathy.","authors":"David A Tess,&nbsp;Tristan S Maurer,&nbsp;Zhenhong Li,&nbsp;Christine Bulawa,&nbsp;James Fleming,&nbsp;Amy T Moody","doi":"10.1080/13506129.2022.2145876","DOIUrl":"https://doi.org/10.1080/13506129.2022.2145876","url":null,"abstract":"<p><strong>Background: </strong>Tafamidis inhibits progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) by binding TTR tetramer and inhibiting dissociation to monomers capable of denaturation and deposition in cardiac tissue. While the phase 3 ATTR-ACT trial demonstrated the efficacy of tafamidis, the degree to which the approved dose captures the full potential of the mechanism has yet to be assessed.</p><p><strong>Methods: </strong>We developed a model of dynamic TTR concentrations in plasma to relate TTR occupancy by tafamidis to TTR stabilisation. We then developed population pharmacokinetic-pharmacodynamic models to characterise the relationship between stabilisation and measures of disease progression.</p><p><strong>Results: </strong>Modelling individual patient data of tafamidis exposure and increased plasma TTR confirmed that single-site binding provides complete tetramer stabilisation <i>in vivo</i>. The approved dose was estimated to reduce unbound TTR tetramer by 92%, and was associated with 53%, 56% and 49% decreases in the rate of change in NT-proBNP, KCCQ-OS, and six-minute walk test disease progression measures, respectively. Simulating complete TTR stabilisation predicted slightly greater reductions of 58%, 61% and 54%, respectively.</p><p><strong>Conclusions: </strong>These findings support the value of TTR stabilisation as a clinically beneficial treatment option in ATTR-CM and the ability of tafamidis to realise nearly the full therapeutic benefit of this mechanism.</p><p><strong>Clinicaltrials.gov identifier: </strong>NCT01994889.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"208-219"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161693","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":"Characterising diflunisal as a transthyretin kinetic stabilizer at relevant concentrations in human plasma using subunit exchange.","authors":"Felix J Tsai, Luke T Nelson, Gabriel M Kline, Marcus Jäger, John L Berk, Yoshiki Sekijima, Evan T Powers, Jeffery W Kelly","doi":"10.1080/13506129.2022.2148094","DOIUrl":"10.1080/13506129.2022.2148094","url":null,"abstract":"<p><p>Transthyretin (TTR) dissociation is the rate limiting step for both aggregation and subunit exchange. Kinetic stabilisers, small molecules that bind to the native tetrameric structure of TTR, slow TTR dissociation and inhibit aggregation. One such stabiliser is the non-steroidal anti-inflammatory drug (NSAID), diflunisal, which has been repurposed to treat TTR polyneuropathy. Previously, we compared the efficacy of diflunisal, tafamidis, tolcapone, and AG10 as kinetic stabilisers for transthyretin. However, we could not meaningfully compare diflunisal because we were unsure of its plasma concentration after long-term oral dosing. Herein, we report the diflunisal plasma concentrations measured by extraction, reversed phase HPLC separation, and fluorescence detection after long-term 250 mg BID oral dosing in two groups: a placebo-controlled diflunisal clinical trial group and an open-label Japanese polyneuropathy treatment cohort. The measured mean diflunisal plasma concentration from both groups was 282.2 <math><mi>μ</mi></math>M <math><mo>±</mo><mi> </mi></math>143.7 <math><mi>μ</mi></math>M (mean <math><mo>±</mo></math> standard deviation). Thus, quantification of TTR kinetic stabilisation using subunit exchange was carried out at 100, 200, 300, and 400 <math><mtext>μM diflunisal</mtext></math> concentrations, all observed in patients after 250 mg BID oral dosing. A 250 <math><mi>μ</mi></math>M diflunisal plasma concentration reduced the wild-type TTR dissociation rate in plasma by 95%, which is sufficient to stop transthyretin aggregation, consistent with the clinical efficacy of diflunisal for ameliorating transthyretin polyneuropathy.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"220-224"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144286","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}

{"title":"An additive destabilising effect of compound T60I and V122I substitutions in ATTRv amyloidosis.","authors":"Tatiana Prokaeva,&nbsp;Elena S Klimtchuk,&nbsp;Polina Feschenko,&nbsp;Brian Spencer,&nbsp;Haili Cui,&nbsp;Eric J Burks,&nbsp;Roshanak Aslebagh,&nbsp;Khaja Muneeruddin,&nbsp;Scott A Shaffer,&nbsp;Elizabeth Varghese,&nbsp;John L Berk,&nbsp;Lawreen H Connors","doi":"10.1080/13506129.2022.2135988","DOIUrl":"https://doi.org/10.1080/13506129.2022.2135988","url":null,"abstract":"<p><strong>Background: </strong>The amyloidogenic transthyretin (TTR) variant, V122I, occurs in 4% of the African American population and frequently presents as a restricted cardiomyopathy. While heterozygosity for TTR V122I predominates, several compound heterozygous cases have been previously described. Herein, we detail features of ATTRv amyloidosis associated with novel compound heterozygous TTR mutation, T60I/V122I and provide evidence supporting the amyloidogenecity of T60I.</p><p><strong>Methods: </strong>A 63-year-old African American female presented with atrial fibrillation, congestive heart failure, autonomic and peripheral neuropathy. <i>In vitro</i> studies of TTR T60I and V122I were undertaken to compare the biophysical properties of the proteins.</p><p><strong>Results: </strong>Congophilic deposits in a rectal biopsy were immunohistochemically positive for TTR. Serum screening by isoelectric focussing revealed two TTR variants in the absence of wild-type protein. DNA sequencing identified compound heterozygous <i>TTR</i> gene mutations, c.239C > T and c.424G > A. Adipose amyloid deposits were composed of both T60I and V122I. While kinetic stabilities of T60I and V122I variants were similar, distinct thermodynamic stabilities and amyloid growth kinetics were observed.</p><p><strong>Conclusions: </strong>This report provides clinical and experimental results supporting the amyloidogenic nature of a novel TTR T60I variant. <i>In vitro</i> data indicate that the destabilising effect of individual T60I and V122I variants appears to be additive rather than synergistic.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"141-152"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161660","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":"Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases.","authors":"Angela Dispenzieri,&nbsp;Jeffrey Zonder,&nbsp;James Hoffman,&nbsp;Sandra W Wong,&nbsp;Michaela Liedtke,&nbsp;Rafat Abonour,&nbsp;Anita D'Souza,&nbsp;Charlene Lee,&nbsp;Sarah Cote,&nbsp;Ravi Potluri,&nbsp;Eric Ammann,&nbsp;NamPhuong Tran,&nbsp;Annette Lam,&nbsp;Sandhya Nair","doi":"10.1080/13506129.2022.2137400","DOIUrl":"https://doi.org/10.1080/13506129.2022.2137400","url":null,"abstract":"<p><strong>Background: </strong>This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis.</p><p><strong>Methods: </strong>Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method.</p><p><strong>Results: </strong>About 1347 patients (EHR, <i>n</i> = 776; claims, <i>n</i> = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were $19,343 and $105,944 for LOT1, $19,183 and $95,793 for LOT2, and $16,611 and $128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively.</p><p><strong>Conclusion: </strong>AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"161-168"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785346","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":"Quantitative sensory testing: a good tool to identify subclinical neuropathy in ATTRV30M amyloidosis patients?","authors":"Isabel Conceição,&nbsp;Isabel de Castro,&nbsp;Andrés Diaz,&nbsp;José Castro","doi":"10.1080/13506129.2022.2155132","DOIUrl":"https://doi.org/10.1080/13506129.2022.2155132","url":null,"abstract":"<p><strong>Background: </strong>Quantitative sensory testing (QST) has been one of the neurophysiological tools used for follow-up and disease progression assessment in ATTRv amyloidosis. We aimed to detect the utility of QST in identifying subclinical neuropathic involvement in ATTRV30M amyloidosis carriers.</p><p><strong>Methods: </strong>A cohort of ATTRV30M amyloidosis carriers were assessed with vibratory (VDT) and cooling (CDT) detection thresholds and heat pain responses. Subjects were divided into asymptomatic carriers (Group 1), paucisymptomatic carriers (Group 2) and stage 1 ATTRv-PN patients (Group 3). Nonparametric statistics were used for group comparisons.</p><p><strong>Results: </strong>A total of 207 ATTRV30M amyloidosis carriers (83 males) were included. Of these, 113 subjects were asymptomatic and 94 symptomatic carriers. In asymptomatic carriers, CDT and Heat Pain (HP 5.0 and HP 0.5) were significantly lower when compared to both group of symptomatic carriers (<i>p</i> ≤ 0.005). In Group 3, VDT, CDT and HP 5.0 were significantly higher, when compared to Group 2 (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>QST, in particular CDT, HP 5 and HP 0.5 modalities, seems a good tool to identify subclinical neuropathy in ATTRv amyloidosis carriers, with CDT showing a higher sensitivity to detect and early neuropathic involvement.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 2","pages":"239-243"},"PeriodicalIF":5.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9787207","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}