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BMJ Case Reports Jun 2024Acquired factor X (FX) deficiency is a rare but well-documented clinical feature of AL amyloidosis. Patients with FX deficiency can present with clinically significant...
Acquired factor X (FX) deficiency is a rare but well-documented clinical feature of AL amyloidosis. Patients with FX deficiency can present with clinically significant bleeding diathesis due to the adsorption of circulating FX to amyloid fibrils. Here, we report an unusual case of a man in his 60s who presented with 6 months of intermittent bruising, labs demonstrating new FX deficiency, elevated free lambda light chains for underlying AL amyloidosis and concurrent new peroneal vein thrombosis. This is the first report of concurrent thrombotic complications in the setting of AL-amyloid-induced FX deficiency. We discuss the diagnostic and therapeutic conundrum of diagnosing AL amyloidosis with bruising as the leading clinical symptom and the management of acute deep vein thrombosis in the setting of FX deficiency.
Topics: Humans; Male; Venous Thrombosis; Factor X Deficiency; Middle Aged; Immunoglobulin Light-chain Amyloidosis
PubMed: 38839408
DOI: 10.1136/bcr-2024-260169 -
Research in Veterinary Science Aug 2024Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic...
Systemic amyloid light-chain (AL) amyloidosis is an infrequent disease in which amyloid fibrils derived from the immunoglobulin light chain are deposited in systemic organs, resulting in functional impairment. This disease has been notably uncommon in animals, and nonhuman primates have not been reported to develop it. In this study, we identified the systemic AL kappa chain amyloidosis in a captive Bornean orangutan (Pongo pygmaeus) and analyzed its pathogenesis. Amyloid deposits were found severely in the submucosa of the large intestine, lung, mandibular lymph nodes, and mediastinal lymph nodes, with milder lesions in the liver and kidney. Mass spectrometry-based proteomic analysis revealed an abundant constant domain of the immunoglobulin kappa chain in the amyloid deposits. Immunohistochemistry further confirmed that the amyloid deposits were positive for immunoglobulin kappa chains. In this animal, AL amyloidosis resulted in severe involvement of the gastrointestinal submucosa and lymph nodes, which is consistent with the characteristics of AL amyloidosis in humans, suggesting that AL amyloid may have a similar deposition mechanism across species. This report enhances the pathological understanding of systemic AL amyloidosis in animals by providing a detailed characterization of this disease based on proteomic analysis.
Topics: Animals; Pongo pygmaeus; Ape Diseases; Amyloidosis; Immunoglobulin kappa-Chains; Immunoglobulin Light-chain Amyloidosis; Lymph Nodes; Male; Proteomics; Female
PubMed: 38838511
DOI: 10.1016/j.rvsc.2024.105315 -
Hematological Oncology Jul 2024Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world... (Observational Study)
Observational Study
Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.
Topics: Humans; Male; Female; Antibodies, Monoclonal; Aged; Immunoglobulin Light-chain Amyloidosis; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Prospective Studies; Lenalidomide; Bortezomib; Adult; Treatment Outcome
PubMed: 38824453
DOI: 10.1002/hon.3289 -
Lakartidningen May 2024Technical developments have paved the way for the development of ultrasensitive analytical methods that allow for precise quantification of brain-specific proteins in... (Review)
Review
Technical developments have paved the way for the development of ultrasensitive analytical methods that allow for precise quantification of brain-specific proteins in blood samples. Plasma levels of amyloid β, specifically the Aβ42/40 ratio, are reduced in Alzheimer's disease (AD) and show concordance with brain amyloidosis assessed by PET, but the overlap with normal elderly may be too large for reliable use in clinical applications. Plasma phosphorylated tau (P-tau), especially a variant called P-tau217, is markedly increased in the early symptomatic stages of AD but remains normal in other neurodegenerative disorders. Total tau (T-tau) is measurable in blood and shows most promise as a biomarker for acute neuronal injury (e.g. acute traumatic or hypoxic brain injury), where T-tau shows a fast and dramatic increase but does not work well as an AD biomarker due to contributions to blood levels from peripheral tissues. Instead, a novel method for tau protein produced only in the CNS called brain-derived tau (BD-tau) shows promise as a biomarker for AD-type neurodegeneration. Neurofilament light (NFL) levels in blood correlate tightly with levels in CSF and reflect axonal injury irrespective of the underlying cause. Increased blood NFL concentration is found in several neurodegenerative disorders, including AD, but even more so in disorders such as motor neuron disease and frontotemporal dementia. Glial fibrillary acidic protein (GFAP) is expressed with activation of astrocytes, and is mildly increased in AD, but is also very high also in acute brain disorders. These blood tests show promise as tools to identify AD pathophysiology in the first assessment of patients with early cognitive symptoms, also in primary care, to guide clinical management and possible admission to the specialist clinic. A two-step model will result in a very high accuracy to either predict or exclude brain amyloidosis of the Alzheimer type.
Topics: Humans; Alzheimer Disease; Biomarkers; tau Proteins; Amyloid beta-Peptides; Brain; Neurofilament Proteins; Glial Fibrillary Acidic Protein
PubMed: 38818759
DOI: No ID Found -
Journal of Surgical Case Reports May 2024Primary amyloidosis of the conjunctiva and eyelid is a rare and often misdiagnosed condition. It is characterized by the deposition of insoluble amyloid fibrils, which...
Primary amyloidosis of the conjunctiva and eyelid is a rare and often misdiagnosed condition. It is characterized by the deposition of insoluble amyloid fibrils, which are misfolded proteins, in the body. Amyloidosis can be systemic or localized with different types of amyloid fibril proteins identified using mass spectrometry. Ocular involvement in amyloidosis can lead to corneal dystrophies, glaucoma, vitreous opacities, and other symptoms. Diagnosis involves clinical examination and histopathological assessment. Treatment options depend on the extent of involvement and may include surgical excision, glaucoma management, vitrectomy, or liver transplantation in rare cases. We present a rare case of localized conjunctival amyloidosis initially misdiagnosed as pyogenic granuloma, with clinical symptoms of ptosis, periorbital swelling, and conjunctival lesions. The patient underwent excision of the lesions, and subsequent evaluation did not reveal systemic amyloidosis. Ocular amyloidosis requires careful diagnosis and consideration of systemic involvement for appropriate management.
PubMed: 38817793
DOI: 10.1093/jscr/rjae356 -
Current Heart Failure Reports May 2024Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA... (Review)
Review
PURPOSE OF REVIEW
Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid.
RECENT FINDINGS
The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy.
PubMed: 38809394
DOI: 10.1007/s11897-024-00669-7 -
Clinical Lymphoma, Myeloma & Leukemia May 2024Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in...
BACKGROUND
Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited.
PATIENTS AND METHODS
A retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients.
RESULTS
The median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure.
CONCLUSION
The hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.
PubMed: 38806310
DOI: 10.1016/j.clml.2024.05.004 -
Therapeutic Advances in Respiratory... 2024Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings.
BACKGROUND
Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings.
OBJECTIVES
To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images.
DESIGN
We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation.
METHODS
Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs).
RESULTS
We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%.
CONCLUSION
We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.
Topics: Humans; Bronchoscopy; Tracheal Diseases; Middle Aged; Male; Female; Adult; Diagnosis, Differential; Predictive Value of Tests; Osteochondrodysplasias; Reproducibility of Results; Deep Learning; Aged; China; Image Interpretation, Computer-Assisted; Neural Networks, Computer; Artificial Intelligence
PubMed: 38803144
DOI: 10.1177/17534666241253694 -
CMAJ : Canadian Medical Association... May 2024
Topics: Humans; Amyloidosis; Blister; Immunoglobulin Light Chains; Male; Female; Oral Hemorrhage; Aged; Immunoglobulin Light-chain Amyloidosis; Middle Aged
PubMed: 38802132
DOI: 10.1503/cmaj.240119 -
Cureus Apr 2024Cardiac amyloidosis can be grouped into two main categories: immunoglobulin light chain (AL) and transthyretin (hATTR or hereditary and ATTRwt or wild type). Cardiac...
Cardiac amyloidosis can be grouped into two main categories: immunoglobulin light chain (AL) and transthyretin (hATTR or hereditary and ATTRwt or wild type). Cardiac infiltration of misfolded proteins can lead to significant infiltrative processes and subsequent heart failure. Diagnosis of ATTRwt heavily relies on clinical suspicion, as it typically appears later in life and is limited to the heart. It is routinely reported that ATTRwt significantly affects males more than females; however, older patients diagnosed with ATTRwt and those diagnosed at autopsy are significantly more likely to be female. Earlier, a more precise diagnosis in females could detect disease at an earlier stage and expedite treatment.
PubMed: 38800288
DOI: 10.7759/cureus.59058