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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 -
Blood Cancer Journal May 2024It is well-established that most patients with systemic light chain (AL) amyloidosis have multi-organ involvement and are often diagnosed after a lag period of...
It is well-established that most patients with systemic light chain (AL) amyloidosis have multi-organ involvement and are often diagnosed after a lag period of increasing symptoms. We leverage electronic health record (EHR) data from the TriNetX research network to describe the incidence, timing, and co-occurrence of precursor conditions of interests in a cohort of AL amyloidosis patients identified between October 2015-December 2020. Nineteen precursor diagnoses of interest representing features of AL amyloidosis were identified using ICD codes up to 36 months prior to AL amyloidosis diagnosis. Among 1,401 patients with at least 36 months of EHR data prior to AL amyloidosis diagnosis, 46% were females, 16% were non-Hispanic Black, and 6% were Hispanic. The median age was 71 (range, 21-91) years. The median number of precursor diagnoses was 5 with dyspnea and fatigue being the most prevalent. The time from the first occurrence of a precursor to AL diagnosis ranged from 3.2 to 21.4 months. Analyses of pairwise co-occurrence of specific diagnoses indicated a high association (Cole's coefficient >0.6) among the examined precursor diagnoses. These findings provide novel information about the timing and co-occurrence of key precursor conditions and could be used to develop algorithms for early identification of AL amyloidosis.
Topics: Humans; Female; Male; Aged; Immunoglobulin Light-chain Amyloidosis; Middle Aged; Adult; Aged, 80 and over; Young Adult; Time Factors; Electronic Health Records
PubMed: 38796476
DOI: 10.1038/s41408-024-01040-8 -
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 -
International Journal of Biological... Jun 2024Light chain amyloidosis is a conformational disease caused by the abnormal proliferation and deposition of antibody light chains as amyloid fibers in organs and tissues....
Light chain amyloidosis is a conformational disease caused by the abnormal proliferation and deposition of antibody light chains as amyloid fibers in organs and tissues. The effect of Cu(II) binding to the model recombinant protein 6aJL2-R24G was previously characterized in our group, and we found an acceleration of the aggregation kinetics of the protein. In this study, in order to confirm the Cu(II) binding sites, histidine variants of 6aJL2-R24G were prepared and the effects of their interaction with Cu(II) were analyzed by circular dichroism, fluorescence spectroscopy, isothermal calorimetry titrations, and molecular dynamics simulations. Confirming our earlier work, we found that His8 and His99 are the highest affinity Cu(II) binding sites, and that Cu(II) binding to both sites is a cooperative event.
Topics: Copper; Histidine; Humans; Protein Binding; Binding Sites; Molecular Dynamics Simulation; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Kinetics
PubMed: 38761898
DOI: 10.1016/j.ijbiomac.2024.132393 -
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