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PloS One 2024Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress.
BACKGROUND
Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress.
METHODS
Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program.
RESULTS
118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need.
CONCLUSION
The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.
Topics: Humans; Female; Male; Aged; Germany; Amyloidosis; Middle Aged; Aged, 80 and over; Surveys and Questionnaires; Quality of Life; Caregivers; Delayed Diagnosis
PubMed: 38768126
DOI: 10.1371/journal.pone.0297182 -
Clinical Case Reports May 2024Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal...
Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal segmental glomerulosclerosis (FSGS) is less common, it should still be in the differential regardless of the patient's clinical profile.
PubMed: 38751961
DOI: 10.1002/ccr3.8901 -
Cureus Apr 2024Lipoid lesions of the thyroid gland are very rare. Fat-containing thyroid lesions include a variety of clinical-pathological disorders, such as adenolipomas,...
Lipoid lesions of the thyroid gland are very rare. Fat-containing thyroid lesions include a variety of clinical-pathological disorders, such as adenolipomas, thyrolipomatosis, and lipomatous tissue, in the event of amyloidosis. Herein, we report a case of diffuse thyrolipomatosis with amyloidosis and incidentally detected papillary carcinoma of the thyroid in a 51-year-old female patient who clinically presented with a multinodular goiter. Amyloidosis in papillary carcinoma of the thyroid is very rare and can be primary or secondary amyloidosis. Thyrolipomatosis, amyloid goiter, and papillary carcinoma of the thyroid is a rare combination, and to our knowledge, this is the third reported case in the literature. The association of amyloidosis and the rare occurrence of a differentiated carcinoma have to be considered, as in the case of thyroid lipomatosis.
PubMed: 38725741
DOI: 10.7759/cureus.57896 -
Transplantation Proceedings May 2024There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage...
BACKGROUND
There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience.
METHODS
Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients.
RESULTS
Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique.
CONCLUSIONS
CLKTx is safe and effective in the treatment of both liver and kidney failure.
Topics: Humans; Kidney Transplantation; Male; Adult; Liver Transplantation; Female; Middle Aged; Treatment Outcome; Young Adult; Kidney Failure, Chronic; Retrospective Studies; Graft Survival
PubMed: 38719623
DOI: 10.1016/j.transproceed.2024.03.014 -
Blood Reviews Jul 2024Amyloid light-chain (AL) amyloidosis is a rare hematological disease that produces abnormal monoclonal immunoglobulin light chains to form amyloid fibrils that are... (Review)
Review
Amyloid light-chain (AL) amyloidosis is a rare hematological disease that produces abnormal monoclonal immunoglobulin light chains to form amyloid fibrils that are deposited in tissues, resulting in organ damage and dysfunction. Advanced AL amyloidosis has a very poor prognosis with a high risk of early mortality. The combination of anti-plasma cell therapy and amyloid fibrils clearance is the optimal treatment strategy, which takes into account both symptoms and root causes. However, research on anti-amyloid fibrils lags far behind research on anti-plasma cells, and there is currently no approved treatment that could clear amyloid fibrils. Nevertheless, anti-amyloid fibril therapies are being actively investigated recently and have shown potential in clinical trials. In this review, we aim to outline the preclinical work and clinical efficacy of fibril-directed therapies for AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloid; Animals
PubMed: 38692939
DOI: 10.1016/j.blre.2024.101207 -
Korean Journal of Radiology May 2024Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization,...
OBJECTIVE
Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA.
MATERIALS AND METHODS
In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed.
RESULTS
Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; = 0.01) compared with those with inferior response.
CONCLUSION
Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.
Topics: Humans; Male; Middle Aged; Female; Prospective Studies; Cardiomyopathies; Magnetic Resonance Imaging; Feasibility Studies; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Treatment Outcome; Magnetic Resonance Imaging, Cine; Antineoplastic Agents
PubMed: 38685733
DOI: 10.3348/kjr.2023.0985 -
Medicina (Kaunas, Lithuania) Apr 2024: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic...
: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. : This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. : A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary ( = 0.003) and the secondary outcome of pacemaker implantation ( = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance ( = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. : CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.
Topics: Humans; Male; Pilot Projects; Female; Cardiomyopathies; Amyloidosis; Aged; Cicatrix; Retrospective Studies; Middle Aged; Magnetic Resonance Imaging; Software
PubMed: 38674259
DOI: 10.3390/medicina60040613 -
Cancers Apr 2024Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to... (Review)
Review
Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients.
PubMed: 38672686
DOI: 10.3390/cancers16081605 -
Cancers Apr 2024Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light...
Outcomes of Modified Mayo Stage IIIa and IIIb Cardiac Light-Chain Amyloidosis: Real-World Experience in Clinical Characteristics and Treatment-67 Patients Multicenter Analysis.
Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50-70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment.
PubMed: 38672674
DOI: 10.3390/cancers16081592 -
American Heart Journal Plus :... May 2024Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As...
STUDY OBJECTIVES
Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself.
DESIGN
Prospective observational study.
SETTING
Medeniyet University Goztepe Hospital.
PARTICIPANTS
61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls.
INTERVENTIONS
Subjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT).
MAIN OUTCOME MEASURES
Comparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis.
RESULTS
Patients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, < 0.05 for both) and CFVR (2.4 (2.1-2.8) in CTS and 1.8 (1.6-2.1) in CTS-A groups, < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60-0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A.
CONCLUSION
Most arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis.
PubMed: 38655035
DOI: 10.1016/j.ahjo.2024.100393