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JNMA; Journal of the Nepal Medical... Oct 2023Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in...
UNLABELLED
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease.
KEYWORDS
cardiomyopathies; case reports; primary amyloidosis.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Bortezomib; Renal Insufficiency; Prognosis
PubMed: 38289775
DOI: 10.31729/jnma.8297 -
International Journal of Cardiology Apr 2024Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in...
AIM
Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in amyloidosis-related hospitalizations (AH) in Veneto Region (5 million inhabitants, Northeastern Italy).
METHODS
International Classification of Diseases (ICD-9) codes were used to identify AH in Veneto from 2010 to 2020. AH were defined as any hospitalization with a discharge summary reporting an ICD-9 code for systemic amyloidosis. Hospitalization for CA was defined as records with ICD-9 code for systemic amyloidosis and ICD-9 code for heart failure,cardiomyopathy or arrhythmia. Hospital/outpatient encounters for carpal tunnel syndrome (CTS) surgeries also were extracted. AH incidence was estimated using a buffer of 5 years.
RESULTS
In the time range 2015-2020, the incidence rate of AH was 23.5 cases per 10 (95% confidence interval, CI, 21.8; 25.3), mainly affecting patients>65 years (76.2%) and males (63.5%), with a progressively increasing trend (percent annual increase 17%, 95% CI 12; 22%). The 10 year prevalence of AH in 2020 was 124.5 per 10 (95% CI 114.9; 134.8). In 2020, annual hospitalized prevalent cases of CA were about 70% of all cases (159/228), mainly patients >65 years and males. Among patients with multiple CTS surgeries, a subsequent code for cardiac disease was found in 913 after a median of 3.9 years, more frequently in men than in women (463/6.526 7.1% versus 450/11.406 3.9%).
CONCLUSIONS
In Veneto, we recorded a significantly increasing trend in the incidence of AH, with concordant increasing prevalence estimates.
Topics: Male; Humans; Female; Hospitalization; Amyloidosis; Heart Failure; Cardiomyopathies; Immunoglobulin Light-chain Amyloidosis; Italy
PubMed: 38262481
DOI: 10.1016/j.ijcard.2024.131804 -
Life (Basel, Switzerland) Dec 2023Light-chain amyloidosis (AL) is a disease of protean manifestations due to a wide spectrum of organs that can be affected. The disorder is caused by the deposition of an... (Review)
Review
Light-chain amyloidosis (AL) is a disease of protean manifestations due to a wide spectrum of organs that can be affected. The disorder is caused by the deposition of an extracellular amorphous material, the amyloid, which is produced by malignant plasma cells. The latter usually reside in the bone marrow; plasma cell infiltration is often low, in sharp contrast to what we observe in multiple myeloma. The disease may run below the physician's radar for a while before clinical suspicion is raised and targeted tests are performed. In this short review, we try to answer most of the questions that a practicing physician may ask in a relative clinical setting. The text is formed as a series of reader-friendly questions that cover the subject of AL amyloidosis from history to current therapy.
PubMed: 38255657
DOI: 10.3390/life14010042 -
Blood Cancer Journal Jan 2024
Topics: Humans; Primary Myelofibrosis; Megakaryocytes; Disease Progression; Mutation; Receptors, CXCR4
PubMed: 38253566
DOI: 10.1038/s41408-024-00991-2 -
Diagnostics (Basel, Switzerland) Jan 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants ( = 10) and nuclear imaging technicians ( = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient's echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.
PubMed: 38248088
DOI: 10.3390/diagnostics14020212 -
The American Journal of Case Reports Jan 2024BACKGROUND Systemic light chain (AL) amyloidosis is a disease characterized by the deposition of amyloid fibrils throughout tissues due to the production of misfolded...
BACKGROUND Systemic light chain (AL) amyloidosis is a disease characterized by the deposition of amyloid fibrils throughout tissues due to the production of misfolded immunoglobulin light chains by clonally expanded populations of CD38+ plasma cells. Some patients can have liver involvement, which typically presents with nonspecific symptoms. Daratumumab, a human CD38-targeting antibody, has shown efficacy in improving hematological parameters and organ function in patients with AL amyloidosis. Low-frequency daratumumab can reduce financial burden, but whether it is effective for patients with liver involvement has not been reported. CASE REPORT We present the case of a 64-year-old man admitted to our hospital with fatigue and recurrent fever. Histological analysis of a liver biopsy demonstrated AL amyloidosis. Bone marrow biopsy demonstrated the presence of abnormal plasma cells. Laboratory test results demonstrated increased levels of circulating free kappa (kappa) light chains, which were also seen on blood and urine immunofixation electrophoresis. Based on these findings, AL amyloidosis of the kappa light chain type with liver, cardiac, and renal involvement was diagnosed. The patient ultimately achieved hematological stringent complete response, liver remission, renal complete response, and cardiac very good partial response after 2 cycles of the low-frequency daratumumab, bortezomib, and dexamethasone regimen and 4 cycles of daratumumab and dexamethasone regimen chemotherapy. CONCLUSIONS The case indicates that low-frequency daratumumab treatment can have efficacy in AL amyloidosis with liver involvement.
Topics: Male; Humans; Middle Aged; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Antibodies, Monoclonal; Dexamethasone
PubMed: 38229422
DOI: 10.12659/AJCR.942534 -
Blood Science (Baltimore, Md.) Jan 2024Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression...
Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation (VISTA), programmed cell death 1 (PD-1), T cell immunoglobulin and mucin-domain-containing-3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA and PD-1 T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1 and TIGIT T cells than the patients without, and PD-1CD3%, PD-1CD4%, PD-1Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1 Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA and PD-1 T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1 and TIGIT T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.
PubMed: 38226018
DOI: 10.1097/BS9.0000000000000181 -
Haematologica May 2024
Limited utility of Mayo 2012 cardiac staging system for risk stratification of patients with advanced cardiac AL amyloidosis - analysis of a uniformly treated cohort of 1,275 patients.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Female; Male; Aged; Risk Assessment; Middle Aged; Prognosis; Cohort Studies
PubMed: 38205538
DOI: 10.3324/haematol.2023.284348 -
European Journal of Medical Research Jan 2024Transthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of...
BACKGROUND
Transthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using Tc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods.
METHODS
Twenty-seven patients at Nagasaki University Hospital who underwent Tc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness.
RESULTS
Among patients who underwent Tc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h).
CONCLUSION
Our study suggests that both 1-h and 3-h incubation times for Tc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity.
Topics: United States; Aged; Humans; Technetium Tc 99m Pyrophosphate; Diagnostic Imaging; Amyloidosis; Heart; Heart Failure
PubMed: 38184638
DOI: 10.1186/s40001-023-01629-y -
Therapeutics and Clinical Risk... 2023Systemic AL amyloidosis, a plasma cell dyscrasia, is characterized by the production of misfolded immunoglobulin light chain. These misfolded proteins aggregate into... (Review)
Review
INTRODUCTION
Systemic AL amyloidosis, a plasma cell dyscrasia, is characterized by the production of misfolded immunoglobulin light chain. These misfolded proteins aggregate into amyloid fibrils and deposit throughout the body, resulting in widespread organ dysfunction and ultimately death. Achieving rapid and maximal elimination of the plasma cell clone is crucial to long-term survival. Daratumumab, an anti-CD38 monoclonal antibody delivered intravenously, has been swiftly incorporated into standard first-line treatment regimens. A novel formulation of daratumumab has been developed that can be injected subcutaneously.
AREAS COVERED
As a retrospective qualitative review of prior publications involving daratumumab, this work briefly summarizes the existing data regarding the safety and efficacy of subcutaneous (SC) daratumumab, compared to intravenous (IV) daratumumab. SC daratumumab appears to deliver the same disease benefit as IV daratumumab to patients with decreased infusion-related reactions (IRRs), decreased time for administration, and similar rates of adverse events (AEs) intrinsically related to daratumumab.
EXPERT OPINION
SC daratumumab is preferred over IV daratumumab, but the clinical situation ultimately should determine route of administration. Further investigation into cost-effectiveness benefit is warranted.
PubMed: 38164204
DOI: 10.2147/TCRM.S325859