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Annals of Clinical Biochemistry Jan 2022Prealbumin is a small protein which has been widely evaluated as a nutritional and a prognostic marker. The small size and concentration of prealbumin in blood proposes... (Review)
Review
Prealbumin is a small protein which has been widely evaluated as a nutritional and a prognostic marker. The small size and concentration of prealbumin in blood proposes challenges on measuring it with high sensitivity and specificity. Over the years, a number of analytical methodologies have been developed, which may help establish prealbumin as a useful biomarker in routine clinical practice. The aim of the short review was to explore the current literature on the clinical utility of prealbumin and the advances made in the analytical methodologies of prealbumin. We searched MEDLINE, EMBASE and the Cochrane Library for articles published between January 1980 and July 2019, with the general search terms of 'prealbumin', 'prognostic marker', 'nutritional marker', 'analytical methodologies' and 'malnutrition'. Additionally, we selected relevant articles and comprehensive overviews from reference lists of identified studies. The routine use of prealbumin in clinical practice remains debatable; however; it can complement clinical history, anthropometric assessment and physical examination to assess malnutrition with more certainty. Consensus on the clinical applications of prealbumin in the management of malnutrition is warranted.
Topics: Anthropometry; Biomarkers; Humans; Malnutrition; Nutritional Status; Prealbumin
PubMed: 32429677
DOI: 10.1177/0004563220931885 -
Acta Neurologica Scandinavica Feb 2019Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder,...
Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).
Topics: Amyloid Neuropathies, Familial; Humans; Mutation; Prealbumin
PubMed: 30295933
DOI: 10.1111/ane.13035 -
Current Cardiology Reports Aug 2017Transthyretin (TTR)-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive, hypertrophic heart disease and may go undiagnosed.... (Review)
Review
PURPOSE OF REVIEW
Transthyretin (TTR)-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive, hypertrophic heart disease and may go undiagnosed. Transthyretin-derived amyloidosis accounts for 18% of all cases of cardiac amyloidosis. Thus, the study's purpose is to provide a comprehensive review of transthyretin cardiac amyloidosis.
RECENT FINDINGS
Wild-type transthyretin (ATTRwt) protein causes cardiac amyloidosis sporadically, with 25 to 36% of the population older than 80 years of age are at risk to develop a slowly progressive, infiltrative amyloid cardiomyopathy secondary to ATTRwt. In contrast, hereditary amyloidosis (ATTRm) is an autosomal dominant inherited disease associated with more than 100 point mutations in the transthyretin gene and has a tendency to affect the heart and nervous system. Up to 4% of African-Americans carry the Val122Ile mutation in the transthyretin gene, the most prevalent cause of hereditary cardiac amyloidosis in the USA. Identifying transthyretin cardiac amyloidosis requires increased awareness of the prevalence, signs and symptoms, and diagnostic tools available for discrimination of this progressive form of cardiomyopathy associated with left ventricular hypertrophy. While there are no FDA-approved medical treatments, investigation is underway on agents to reduce circulating mutated transthyretin.
Topics: Amyloidosis; Amyloidosis, Familial; Cardiomyopathies; Humans; Point Mutation; Prealbumin
PubMed: 28840452
DOI: 10.1007/s11886-017-0911-5 -
Heart Failure Reviews Mar 2024Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease characterized by the deposition of abnormal transthyretin protein fibrils in the heart, leading to... (Review)
Review
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease characterized by the deposition of abnormal transthyretin protein fibrils in the heart, leading to cardiac dysfunction. Recent evidence suggests that sex differences may play a significant role in various steps of ATTR-CA, including clinical presentation, diagnostic challenges, disease progression, and treatment outcomes. ATTR-CA predominantly affects men, whereas women are older at presentation. Women generally present with a history of heart failure with preserved ejection fraction and/or carpal tunnel syndrome. When indexed, left ventricular (LV) wall thickness is equal, or even increased, than men. Women also have smaller LV cavities, more preserved ejection fractions, and apparently a slightly worse right ventricular and diastolic function. Given the under-representation on women in clinical trials, no data regarding sex influence on the treatment response are currently available. Finally, it seems there are no differences in overall prognosis, even if premenopausal women may have a certain level of myocardial protection. Genetic variations, environmental factors, and hormonal changes are considered as potential contributors to observed disparities. Understanding sex differences in ATTR-CA is vital for accurate diagnosis and management. By considering these differences, clinicians can improve diagnostic accuracy, tailor treatments, and optimize outcomes for both sexes with ATTR-CA.
Topics: Humans; Female; Male; Cardiomyopathies; Prealbumin; Sex Characteristics; Amyloidosis; Heart; Amyloid Neuropathies, Familial
PubMed: 37566193
DOI: 10.1007/s10741-023-10339-w -
The American Journal of the Medical... Aug 2023
Topics: Humans; Prealbumin; Amyloidosis; Cardiomyopathies
PubMed: 37001694
DOI: 10.1016/j.amjms.2023.03.023 -
American Journal of TherapeuticsDeposition of wild-type or mutant transthyretin (TTR) amyloid fibrils in the myocardium causes TTR amyloid cardiomyopathy (ATTR-CM). Targeted therapeutics for ATTR-CM...
BACKGROUND
Deposition of wild-type or mutant transthyretin (TTR) amyloid fibrils in the myocardium causes TTR amyloid cardiomyopathy (ATTR-CM). Targeted therapeutics for ATTR-CM include TTR stabilizers (tafamidis and diflunisal) and oligonucleotide drugs (revusiran, patisiran, and inotersen). TTR stabilizers prevent dissociation of transthyretin tetramers. Transthyretin monomers can misfold and form amyloid fibrils. TTR stabilizers thereby limit amyloid fibrils development and deposition. Oligonucleotide drugs inhibit hepatic synthesis of transthyretin, which decreases transthyretin protein levels and thus the amyloid fibril substrate.
AREAS OF UNCERTAINTY
To study the safety and efficacy of targeted therapeutics in patients with ATTR-CM, we performed a pooled analysis. A random-effects model with the Mantel-Haenszel method was used to pool the data.
DATA SOURCES
A literature search was performed using PubMed, Cochrane CENTRAL, and Embase databases using the search terms "cardiac amyloidosis" AND "tafamidis" OR "patisiran" OR "inotersen" OR "revusiran" OR "diflunisal."
THERAPEUTIC ADVANCES
We identified 6 studies that compared targeted therapeutics with placebo. One study was stopped prematurely because of increased mortality in the targeted therapeutics arm. Pooled analysis included 1238 patients, of which 738 patients received targeted therapeutics and 500 patients received placebo. When compared with placebo, targeted therapeutics significantly reduced all-cause mortality [OR 0.39, 95% confidence interval (CI): 0.16-0.97, P = 0.04]. Only 2 studies reported the effect on cardiovascular-related hospitalizations. There was a trend toward an improvement in global longitudinal strain (mean difference -0.69, 95% CI: -1.44 to 0.05, P = 0.07). When compared with placebo, there was no increase in serious adverse events with targeted therapeutics (OR 1.06, 95% CI: 0.78-1.44, P = 0.72).
CONCLUSION
Evidence from the pooled analysis revealed targeted therapeutics improve survival and are well-tolerated. These findings suggest a potential role for targeted therapeutics in the treatment of patients with ATTR-CM.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Diflunisal; Oligonucleotides; Cardiomyopathies
PubMed: 37713689
DOI: 10.1097/MJT.0000000000001296 -
Journal of the American College of... Jul 2019
Topics: Amyloidosis; Cardiomyopathies; Humans; Prealbumin
PubMed: 31319911
DOI: 10.1016/j.jacc.2019.05.031 -
Global Heart 2023Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of...
Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of heart failure and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CA, which is now possible without recourse to endomyocardial biopsy in around 70% of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CA and more accurate prognostic stratification. Therapies able to slow or halt ATTR-CA progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional heart failure medications. A wide horizon of possibilities is unfolding and awaits discovery.
Topics: Humans; Prealbumin; Amyloidosis; Heart Failure; Prognosis; Cardiomyopathies
PubMed: 38028963
DOI: 10.5334/gh.1275 -
European Heart Journal Jul 2022
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Humans; Prealbumin
PubMed: 35639645
DOI: 10.1093/eurheartj/ehac261 -
Nature Communications Jun 2023Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here,...
Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake Ttr mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.
Topics: Mice; Male; Animals; Choroid Plexus; Blood-Brain Barrier; Brain; Thyroid Hormones; Prealbumin; Biological Transport
PubMed: 37349305
DOI: 10.1038/s41467-023-39326-3