-
Diagnostic and Interventional Radiology... Nov 2021Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our study aimed to systematically evaluate the accuracy of bone radiotracers for diagnosis and differentiation of TTR-CA via a systematic review and meta-analysis.
METHODS
We retrieved articles assessing the performance of bone tracer in diagnosing and differentiating TTR-CA from PubMed, the Cochrane Library, ScienceDirect, and DOAJ databases, dating up to 10 July 2020. The meta-analysis was conducted through Stata 16 software, and the risk of bias for the included studies was assessed by the QUADAS-2 tool. Moreover, we made a comprehensive review.
RESULTS
Fourteen articles were included in the systematic review, and 9 in the meta-analysis. The pooled sensitivity was 0.97 (95% confidence interval [95% CI] 0.85-0.99) with heterogeneity (I2=73.5, 95% CI 55.6-91.2), and the specificity was 0.92 (95% CI 0.82-0.96) with heterogeneity (I2=42.0, 95% CI 0.0-86.9). The pooled positive and negative likelihood ratios were 11.49 (95% CI 5.07-26.0) and 0.03 (95% CI 0.01-0.18), respectively. The diagnostic odds ratio was 341 (95% CI 53-2194), and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.94-0.97).
CONCLUSION
The findings evidence that the bone radiotracer is a valuable noninvasive approach that provides high accuracy for diagnosing TTR-CA and plays a modest role in differentiating TTR-CA from immunoglobulin amyloid light-chain cardiac amyloidosis. 99mTc-HMDP may be more accurate than 99mTc-PYP, 99mTc-DPD, and 18F-NaF in the TTR-CA detecting process, and 18F-NaF is a promising bone tracer to diagnose and differentiate TTR-CA.
Topics: Amyloidosis; Bone and Bones; Heart; Humans; Prealbumin; Radionuclide Imaging
PubMed: 34792038
DOI: 10.5152/dir.2021.20662 -
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 -
Hellenic Journal of Cardiology : HJC =... 2019Light-chain amyloidosis and transthyretin-related amyloidosis (wild-type and mutated) are three main types of systemic amyloidosis associated with a clinically relevant... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Light-chain amyloidosis and transthyretin-related amyloidosis (wild-type and mutated) are three main types of systemic amyloidosis associated with a clinically relevant cardiac involvement. In this study, we compared prognosis in patients with different categories of cardiac amyloidosis using meta-analysis and present a systematic review.
METHODS
A systematic literature search was performed through Jan 1, 2018, and two reviewers independently extracted data and assessed risk of bias. We extracted MACE and death endpoint events and hazard ratios from regression models and performed a meta-analysis of the multiple prognosis association studies.
RESULTS
We observed that there were significant MACE differences between patients diagnosed with transthyretin amyloidosis and light-chain amyloidosis (OR: 2.09; 95% CI: 1.06-4.12; P = 0.03), and the same is true in the sub-comparison between AL and mATTR or wtATTR (AL vs. mATTR: OR: 1.72; 95% CI: 1.06-2.82; P = 0.03; AL vs. wtATTR: OR: 1.48; 95% CI: 0.85-2.58; P = 0.17). However, no significant difference was observed between two transthyretin types (P = 0.17). Overall death rate evaluated showed that compared with transthyretin-related amyloidosis, light-chain type showed a significant difference (P < 0.05). The prognostic analysis showed that types of amyloidosis, LVEF, NYHA, restrictive filling pattern, E-wave deceleration time, E/E' ratio, and low QRS voltage were predictors of cardiac-related mortality.
CONCLUSION
Patients diagnosed with light-chain amyloidosis has a poor prognosis compared with transthyretin-related amyloidosis, while no difference was proved in prognostic analysis between wild-type and mutated TTR amyloidosis. Some clinical factors related to the death prognosis, such as the LVEF, restrictive filling pattern, E-wave deceleration time, and E/E' ratio are important prognostic factors.
Topics: Adult; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Cardiomyopathies; Case-Control Studies; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Prealbumin; Prognosis; Ventricular Function, Left
PubMed: 30742933
DOI: 10.1016/j.hjc.2019.01.015 -
International Journal of Heart Failure Jan 2024Atrial fibrillation is common in patients with cardiac amyloidosis. However, the optimal anticoagulation strategy to prevent thromboembolic events in patients with...
BACKGROUND AND OBJECTIVES
Atrial fibrillation is common in patients with cardiac amyloidosis. However, the optimal anticoagulation strategy to prevent thromboembolic events in patients with cardiac amyloidosis and atrial fibrillation is unknown. This systematic review and meta-analysis compares direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in patients with cardiac amyloidosis and atrial fibrillation.
METHODS
We performed a systematic literature review to identify clinical studies of anticoagulation therapies for patients with cardiac amyloidosis and atrial fibrillation. The primary outcomes of major bleeding and thrombotic events were reported using random effects risk ratios (RRs) with 95% confidence interval (CI).
RESULTS
Our search yielded 97 potential studies and evaluated 14 full-text articles based on title and abstract. We excluded 10 studies that were review articles or did not compare anticoagulation. We included 4 studies reporting on 1,579 patients. The pooled estimates are likely underpowered due to small sample sizes. There was no difference in bleeding events for patients with cardiac amyloidosis and atrial fibrillation treated with DOACs compared to VKAs with a RR of 0.64 (95% CI, 0.38-1.10; p=0.10). There were decreased thrombotic events for patients with cardiac amyloidosis and atrial fibrillation treated with DOACs compared to VKAs with a RR of 0.50 (95% CI, 0.32-0.79; p=0.003).
CONCLUSIONS
This systematic review and meta-analysis suggests that DOACs are as safe and effective as VKAs in patients with cardiac amyloidosis and atrial fibrillation. However, more data are needed to investigate clinical differences in anticoagulation therapy in this patient population.
PubMed: 38303916
DOI: 10.36628/ijhf.2023.0031 -
Scandinavian Journal of Gastroenterology Sep 2021Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated...
PURPOSE
Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated examinations such as full-thickness bowel biopsy. We hypothesized that knowledge about simultaneous occurrence of different types of neuropathy would lead to faster recognition and diagnosis of autonomic/enteric neuropathy. The aim of the present systematic review was to increase the awareness of disease groups causing autonomic and enteric neuropathy along with sensorimotor neuropathy.
METHODS
A systematic search strategy was used in PubMed, Embase and Web of Science. First, 4978 articles were identified. Review of titles/abstracts rendered exclusion of animal studies, articles not written in English or full-length, case reports, conference abstracts and duplicates until 357 articles remained. The full-length evaluation resulted in 35 studies (27 non-systematic reviews) which described objectively verified peripheral autonomic, enteric and sensorimotor neuropathy within the same disease.
RESULTS
Diabetes is the most common disease in society rendering generalized peripheral neuropathy. Accumulation of tissue deposits in amyloidosis, Lewy body disorders and sarcoidosis lead to widespread peripheral neuropathy. Several autoimmune disorders such as systemic sclerosis and primary Sjögren's syndrome present themselves with neuropathy. Paraneoplastic neuropathy may appear prior to symptoms from the malignancy. Both the infection , as well as the autoimmune response to the infection, i.e., Guillain-Barré syndrome, may lead to widespread peripheral neuropathy. Hereditary disorders with disturbed metabolism lead to intermittent attacks of neuropathy.
CONCLUSIONS
The major causes of generalized peripheral neuropathy are diabetes, diseases with tissue deposits, autoimmunity, infections, malignancy and metabolic diseases.
Topics: Animals; Autoimmune Diseases; Guillain-Barre Syndrome; Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases
PubMed: 34214006
DOI: 10.1080/00365521.2021.1942542 -
ESC Heart Failure Oct 2019The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.
METHODS AND RESULTS
MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias.
CONCLUSIONS
Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Diagnosis, Differential; Heart Diseases; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Prevalence; Radionuclide Imaging; Sensitivity and Specificity
PubMed: 31487121
DOI: 10.1002/ehf2.12511 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
European Journal of Haematology Feb 2021Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab...
OBJECTIVES
Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.
METHODS
A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations.
RESULTS
Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria.
CONCLUSIONS
Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Biomarkers; Clinical Trials as Topic; Disease Management; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome
PubMed: 33090552
DOI: 10.1111/ejh.13535 -
BMC Musculoskeletal Disorders Jan 2021Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid...
BACKGROUND
Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid deposits may lead to orthopedic conditions before cardiac manifestations occur. Pharmacologic treatments reduce further amyloid deposits in these patients. Thus, early diagnosis improves long term survival.
QUESTIONS/PURPOSES
The primary purpose of this systematic review was to characterize the association between amyloid deposition and musculoskeletal pathology in patients with common orthopedic conditions. A secondary purpose was to determine the relationship between amyloid positive biopsy in musculoskeletal tissue and the eventual diagnosis of systemic amyloidosis.
METHODS
We performed a systematic review using PRISMA guidelines. Inclusion criteria were level I-IV evidence articles that analyzed light-chain or transthyretin amyloid deposits in common orthopedic surgeries. Study methodological quality, risk of bias, and recommendation strength were assessed using MINORS, ROBINS-I, and SORT.
RESULTS
This systematic review included 24 studies for final analysis (3606 subjects). Amyloid deposition was reported in five musculoskeletal pathologies, including carpal tunnel syndrome (transverse carpal ligament and flexor tenosynovium), hip and knee osteoarthritis (synovium and articular cartilage), lumbar spinal stenosis (ligamentum flavum), and rotator cuff tears (tendon). A majority of studies reported a mean age greater than 70 for patients with TTR or AL positive amyloid.
CONCLUSIONS
This systematic review has shown the presence of amyloid deposition detected at the time of common orthopedic surgeries, especially in patients ≥70 years old. Subtyping of the amyloid has been shown to enable diagnosis of systemic light-chain or transthyretin amyloidosis prior to cardiac manifestations.
LEVEL OF EVIDENCE
Level IV.
Topics: Aged; Amyloid Neuropathies, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Orthopedic Procedures; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 33419417
DOI: 10.1186/s12891-020-03912-z -
Autoimmunity Reviews Feb 2020To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary...
Clinical, morphological features and prognostic factors associated with interstitial lung disease in primary Sjӧgren's syndrome: A systematic review from the Italian Society of Rheumatology.
OBJECTIVE
To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary Sjögren's Syndrome (pSS).
METHODS
Pubmed was searched between February 1996 and December 2018 using a combination of MESH terms related to pSS and ILD. Selected works were subjected to blind evaluation by two authors and a senior author in case of disagreement. The work followed PRISMA guidelines and was registered on PROSPERO (CRD42018118669).
RESULTS
About 20% of pSS patients have ILD, with a 5-y survival of 84% and a need for supplemental oxygen in the 11-33% range. A significant proportion of ILD patients are seronegative without sicca syndrome. ILD seems to be associated with higher levels of Lactic Dehydrogenases and positivity for Anti-Ro52k. The prevalent pattern in High Resolution Computed Tomography is Nonspecific Interstitial Pneumonia (NSIP), but all other patterns can be present. No difference in mortality was found between patients with NSIP and Usual Interstitial Pneumonia patterns. Amyloidosis and primary lung lymphoma can be observed in about 10% of pSS patients.
CONCLUSION
The recognition of pSS underlying an ILD can be challenging in seronegative patients with no or mild sicca symptoms. A complete diagnostic assessment, including minor salivary glands and, in some cases, lung biopsy, should be performed on all patients at risk. A better recognition of the clinical or serological markers of ILD progression in these patients is warranted to drive the physicians to an early diagnosis and an effective treatment.
Topics: Humans; Italy; Lung Diseases, Interstitial; Prognosis; Rheumatology; Sjogren's Syndrome; Societies, Medical
PubMed: 31843713
DOI: 10.1016/j.autrev.2019.102447