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European Archives of... Jul 2023The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery. (Review)
Review
PURPOSE
The aim of this review was to study the surgical management of laryngeal amyloidosis and estimate the rate of recurrence after surgery.
METHODS
A systematic review searching PubMed and EMBASE was performed. A qualitative synthesis of data regarding the surgical management of LA and a quantitative analysis of the recurrence rate after surgery was conducted.
RESULTS
This systematic review included 14 retrospective studies, one of whom is retrospective controlled. A total of 515 subjects were included, the mean age ranged from 43.3 to 58 years with a male-to-female ratio of 1:1.3. All cases had a localized laryngeal amyloidosis. The supraglottic region was the most affected laryngeal site and multiple sites were commonly involved. Surgical treatment consists of endoscopic excision using laser, cold or powered instruments. Open surgery is required for severe primary case or revision surgery. Surgical complications such as granulomatosis scar tissue formation, tracheostomy, laryngotracheal stenosis, pneumothorax and concomitant malignancy were developed in 17.5% of patients. The time onset to diagnosis varied from 1 months to 15 years and the duration of follow-up from 3 months to 25 years. The rate of recurrence was 28.4% (95% CI 24.5-32.6) and the timing of recurrences ranged from 3 months to 10 years.
CONCLUSION
The recurrence rate after primary surgery for laryngeal amyloidosis is high. A tailored surgical treatment based on the disease extension and a long-term follow up are recommended.
Topics: Humans; Male; Female; Adult; Middle Aged; Retrospective Studies; Laryngeal Diseases; Larynx; Laryngostenosis; Amyloidosis
PubMed: 36790723
DOI: 10.1007/s00405-023-07881-6 -
Hematology (Amsterdam, Netherlands) Dec 2023Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and death. Recent studies suggest that hematologic response may be an important prognostic indicator of overall survival (OS) in AL amyloidosis. The aim of this study was to evaluate the trial-level association between hematologic complete response (CR) or very good partial response or better (≥ VGPR) and OS in newly diagnosed patients.
METHODS
Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model.
RESULTS
Nine observational studies reporting hematologic CR or ≥VGPR and OS hazard ratios (HRs) were included in the meta-analysis. Achieving hematologic CR was associated with improved OS (HR, 0.21; 95% confidence interval [CI] 0.13-0.34). Achieving ≥ VGPR was also associated with improved OS (HR 0.21; 95% CI 0.17-0.26). Results of a sensitivity analysis excluding one outlier study revealed no heterogeneity and a better overall HR estimate. Potential limitations of this meta-analysis include the small number of eligible studies (consistent with the rarity of the disease) and inconsistencies in reporting of results.
CONCLUSIONS
Overall, our findings support the use of deep hematologic response (CR or ≥VGPR) as a clinical trial endpoint in newly diagnosed AL amyloidosis. This study provides evidence that early hematologic response is a strong patient-level surrogate for long-term OS in patients with AL amyloidosis receiving frontline therapy. Structured data collection of depth of response in future trials will further strengthen these observations.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Prognosis; Remission Induction; Proportional Hazards Models
PubMed: 36607151
DOI: 10.1080/16078454.2022.2157581 -
Clinical Advances in Hematology &... Oct 2022Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal... (Review)
Review
BACKGROUND
Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA.
OBJECTIVE
We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant.
METHODS
An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review.
RESULTS
Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce.
CONCLUSION
Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.
Topics: Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Transplantation, Autologous; Treatment Outcome
PubMed: 36206073
DOI: No ID Found -
American Journal of Cardiovascular... 2022Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an... (Review)
Review
BACKGROUND
Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.
METHODS
This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction.
RESULTS
Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I=87%) compared with transthyretin negative group.
CONCLUSION
Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.
PubMed: 35873185
DOI: No ID Found -
Orphanet Journal of Rare Diseases Jul 2022Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of...
BACKGROUND
Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition.
METHODS
This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data.
RESULTS
Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively.
CONCLUSIONS
Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.
Topics: Europe; Humans; Immunoglobulin Light-chain Amyloidosis; Incidence; Prevalence; Registries; United States
PubMed: 35854312
DOI: 10.1186/s13023-022-02414-6 -
Cancer Cell International Jul 2022Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered... (Review)
Review
BACKGROUND
Intravenous daratumumab (DARA IV) has been increasingly used in the treatment of amyloid light-chain (AL) amyloidosis. However, the outcomes for patients administered with DARA IV have not been aggregated. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of DARA IV for AL amyloidosis.
METHODS
We searched Medline, EMBASE, Cochrane Library and Web of Science up to 17 June 2021. Response rates and survival rates, and the corresponding 95% confidence intervals (CIs) were pooled and calculated using a fixed-effects model.
RESULTS
Thirty studies (5 cohort studies and 25 single-arm studies) with 997 patients were included. In patients receiving DARA IV-based treatments, very good partial response or better response rate, complete response rate, very good partial response rate, partial response rate and overall response rate were 66% (95% CI, 62-69%), 30% (95% CI, 23-36%), 40% (95% CI, 33-46%), 17% (95% CI, 14-21%), and 77% (95% CI, 73-80%), respectively. Cardiac and renal responses were 41% (95% CI, 34-49%) and 43% (95% CI, 32-54%), respectively. 58% (95% CI, 49-66%) of patients achieved PFS one year or longer. 2.5% (range, 1-10.0%) of patients experienced grade 3 or 4 adverse events, of which the most common adverse event was lymphocytopenia (range, 13.6-25.0%).
CONCLUSION
This study supports the efficacy and safety of DARA IV for the treatment of patients with AL amyloidosis.
PubMed: 35788237
DOI: 10.1186/s12935-022-02635-6 -
Rheumatology (Oxford, England) Dec 2022A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA...
OBJECTIVE
A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet's syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review.
METHODS
We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976-2000 and those registered during 2001-2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS
The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis.
CONCLUSION
The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS.
Topics: Humans; Male; Female; Behcet Syndrome; Retrospective Studies; Follow-Up Studies; Amyloidosis
PubMed: 35657376
DOI: 10.1093/rheumatology/keac223 -
Future Cardiology Jun 2022Aortic stenosis with cardiac amyloidosis (CA-AS) is common in the elderly. We provide an overview and a meta-analysis of outcomes after aortic valve (AV) intervention.... (Meta-Analysis)
Meta-Analysis Review
Aortic stenosis with cardiac amyloidosis (CA-AS) is common in the elderly. We provide an overview and a meta-analysis of outcomes after aortic valve (AV) intervention. The primary end point was all-cause mortality. Weighted pooled analysis showed a non-significant higher risk of death in CA-AS patients following surgical or transcatheter AV replacement. After transcatheter AV replacement, the risk of death in CA-AS patients was comparable to that associated with aortic stenosis alone (risk ratio: 1.23; 95% CI: 0.77-1.96; p = 0.39; I = 0%). An AV intervention is possibly not futile in CA-AS and should not be denied to patients with this condition.
Topics: Aged; Amyloidosis; Aortic Valve; Aortic Valve Stenosis; Humans; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 35420047
DOI: 10.2217/fca-2021-0118 -
ESC Heart Failure Jun 2022Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged... (Review)
Review
Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Contrast Media; Gadolinium; Humans; Prealbumin; Prospective Studies
PubMed: 35343098
DOI: 10.1002/ehf2.13884 -
Journal of Comparative Effectiveness... Apr 2022Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to... (Review)
Review
Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to evaluate the current evidence base in AL amyloidosis. Literature searches on clinical, health-related quality of life, economic and resource use evidence were conducted using the Embase, MEDLINE and Cochrane databases as well as gray literature. This SLR yielded 84 unique studies from: five randomized controlled trials; 54 observational studies; 12 health-related quality of life studies, none with utility values; no economic evaluation studies; and 16 resource use studies, none with indirect costs. This SLR highlights a paucity of published literature relating to randomized controlled trials, utility values, economic evaluations and indirect costs in AL amyloidosis.
Topics: Cost-Benefit Analysis; Databases, Factual; Humans; Immunoglobulin Light-chain Amyloidosis; Publications; Quality of Life
PubMed: 35188424
DOI: 10.2217/cer-2021-0261