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Clinical and Experimental Rheumatology 2020Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or...
OBJECTIVES
Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or prealbumin could be deficitary in SSc.
METHODS
Patients with SSc and very early SSc (veSSc) were prospectively included. Clinical assessment, data recording and quality controls followed EUSTAR standards. The UCLA SCTCGIT 2.0 questionnaire was applied and the serum levels of zinc, selenium, prealbumin, holotranscobalamin, folic acid were measured.
RESULTS
Half (52.4%) of the 176 patients with established SSc showed a deficiency in at least one of the measured nutrients. The most frequent deficit was seen in folic acid (17.9%), followed closely by selenium, prealbumin and zinc (around 15% each). Nearly a fifth (19%) of these patients had multiple deficiencies. Patients with more severe disease, including advanced skin fibrosis, positive ACR 1980 classification criteria, anemia and elevated serum inflammation markers were more likely to be nutrient deficient. Lower BMI<20kg/m2 was associated with several nutrient deficiencies. Prealbumin deficiency was associated with more frequent stomach symptoms and methotrexate therapy. A third of veSSc patients (27%, 44/74) presented a nutrient deficiency, mostly of zinc (10%). Surprisingly, micronutrient deficiencies were not associated with usual parameters of gastrointestinal involvement.
CONCLUSIONS
These novel data reveal deficiencies in micronutrients and/or prealbumin are a frequent burden in patients with SSc. Moreover, these correlate with clinical aspects of the disease. Especially patients with advanced disease appear at high risk for an impaired nutrient status, suggesting that screening of micronutrients status should be performed in these patients.
Topics: Folic Acid; Humans; Micronutrients; Nutritional Status; Prealbumin; Scleroderma, Systemic
PubMed: 32828144
DOI: No ID Found -
Cells Jul 2021Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is... (Review)
Review
Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor. The TTR structure is destabilized by mutations, oxidative modifications, aging, proteolysis, and metal cations, including Ca. Destabilized TTR molecules form amyloid deposits, resulting in senile and familial amyloidopathies. This review links structural stability of TTR with the environmental factors, particularly oxidative stress and Ca, and the processes involved in the pathogenesis of TTR-related diseases. The roles of TTR in biomineralization, calcification, and osteoarticular and cardiovascular diseases are broadly discussed. The association of TTR-related diseases and vascular and ligament tissue calcification with TTR levels and TTR structure is presented. It is indicated that unaggregated TTR and TTR amyloid are bound by vicious cycles, and that TTR may have an as yet undetermined role(s) at the crossroads of calcification, blood coagulation, and immune response.
Topics: Amyloid; Amyloidosis; Animals; Arthritis; Cardiovascular Diseases; Humans; Osteoporosis; Oxidative Stress; Prealbumin; Protein Conformation; Protein Stability
PubMed: 34359938
DOI: 10.3390/cells10071768 -
Nutrients Dec 2022Malnutrition and autonomic dysfunction are associated with poor outcomes, mortality, and psychological problems after stroke. Relevant laboratory biomarkers include...
Malnutrition and autonomic dysfunction are associated with poor outcomes, mortality, and psychological problems after stroke. Relevant laboratory biomarkers include serum albumin, prealbumin, and transferrin. Heart rate variability (HRV), a noninvasive measurement, can objectively measure autonomic nervous system (ANS) function. The relationship between HRV and nutritional biomarkers in stroke patients has not been studied. This study aimed to examine the relationship between nutritional biomarkers and HRV parameters in stroke patients. We retrospectively recruited 426 patients with subacute stroke who were examined for nutritional biomarkers, such as serum albumin, prealbumin, and transferrin, and underwent 24 h ambulatory Holter electrocardiography. Patients were divided into groups according to their nutritional biomarker status. Differences in HRV parameters between nutritional biomarker-deficient and normal groups were assessed. Pearson's correlation and multiple regression analyses were used to verify the relationship between HRV parameters and nutritional biomarkers. HRV parameters were significantly lower in the nutritional biomarker-deficient groups. In addition, there was a significant association between HRV parameters and nutritional biomarkers. Serum albumin, prealbumin, and transferrin levels were associated with ANS function, as measured by HRV, and their deficiency may be a predictive factor for the severity of ANS dysfunction in stroke patients.
Topics: Humans; Prealbumin; Heart Rate; Retrospective Studies; Autonomic Nervous System; Stroke; Biomarkers; Serum Albumin; Transferrins
PubMed: 36558479
DOI: 10.3390/nu14245320 -
Journal of Nuclear Cardiology :... Feb 2023Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual...
INTRODUCTION
Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.
METHODS AND MATERIALS
136 patients received Tc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest.
RESULTS
Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%.
CONCLUSION
We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.
Topics: Humans; Amyloidosis; Cardiomyopathies; Heart; Prealbumin; Single Photon Emission Computed Tomography Computed Tomography; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 35562639
DOI: 10.1007/s12350-022-02960-3 -
Orphanet Journal of Rare Diseases Jun 2022Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin... (Observational Study)
Observational Study
BACKGROUND
Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs.
METHODS
Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021).
RESULTS
This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation.
CONCLUSIONS
This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease.
CLINICALTRIALS
gov Identifier: NCT00628745.
Topics: Amyloid Neuropathies, Familial; Female; Genetic Profile; Humans; Male; Phenotype; Prealbumin; Surveys and Questionnaires
PubMed: 35717381
DOI: 10.1186/s13023-022-02359-w -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
European Journal of Internal Medicine Dec 2020Transthyretin amyloid cardiomyopathy (ATTR-AC) is an under-recognized and underdiagnosed disease. Although traditionally considered a rare condition, the epidemiology of... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-AC) is an under-recognized and underdiagnosed disease. Although traditionally considered a rare condition, the epidemiology of the disease is rapidly changing due to the possibility of non-invasive diagnosis through cardiac scintigraphy with bone tracers and novel disease-modifying treatments providing survival advantages. Nevertheless, many questions and grey areas have to be addressed, such as the natural history of ATTR-AC, the role and implications of genotype-phenotype interactions, the best clinical management, prognostic stratification and the most appropriate treatments, including those already recommended for patients with heart failure. Clinicians have to cope with old beliefs and evolving concepts in ATTR-AC. A wide horizon of possibilities for physicians of many specialties is unfolding and awaits discovery.
Topics: Amyloidosis; Cardiomyopathies; Heart; Heart Failure; Humans; Prealbumin
PubMed: 33032855
DOI: 10.1016/j.ejim.2020.09.025 -
Ugeskrift For Laeger Feb 2020Transthyretin amyloid cardiomyopathy (ATTR-CM) resulting from deposition of transthyretin amyloid fibrils in the heart is an underrecognised cause of heart failure in... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) resulting from deposition of transthyretin amyloid fibrils in the heart is an underrecognised cause of heart failure in the elderly and is associated with a poor life expectancy. The diagnosis can now be made by radionuclide imaging with bone tracers, provided absence of plasma-cell dyscrasia. Recent evidence has suggested a considerable prevalence of ATTR-CM, and effective treatment has become available. This review summarises these new developments, which have ushered a new era in the detection and clinical management of ATTR-CM.
Topics: Aged; Amyloid; Amyloid Neuropathies, Familial; Cardiomyopathies; Heart Failure; Humans; Prealbumin
PubMed: 32089152
DOI: No ID Found -
International Journal of Molecular... Mar 2021Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for...
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.
Topics: Acetates; Amyloid; Amyloid Neuropathies, Familial; Benzothiazoles; Biphenyl Compounds; Drug Design; Humans; Magnetic Resonance Spectroscopy; Methane; Molecular Docking Simulation; Molecular Dynamics Simulation; Permeability; Phenols; Prealbumin; Protein Binding; Protein Folding; Recombinant Proteins; Thyroid Hormones
PubMed: 33800546
DOI: 10.3390/ijms22073488 -
JACC. Heart Failure Feb 2022
Topics: Adult; Amyloid Neuropathies, Familial; Heart; Heart Failure; Humans; Prealbumin; Ventricular Remodeling
PubMed: 35115087
DOI: 10.1016/j.jchf.2021.10.009