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Frontiers of Medicine Aug 2022Transthyretin (TTR) is a small liver-secreted plasma protein that shows close correlations with changes in lean body mass (LBM) during the entire human lifespan and... (Review)
Review
Transthyretin (TTR) is a small liver-secreted plasma protein that shows close correlations with changes in lean body mass (LBM) during the entire human lifespan and agglomerates the bulk of nitrogen (N)-containing substrates, hence constituting the cornerstone of body building. Amino acids (AAs) dietary restriction causes inhibition of TTR production and impairs the accretion of LBM reserves. Inflammatory disorders result in cytokine-induced abrogation of TTR synthesis and urinary leakage of nitrogenous catabolites. Taken together, the data indicate that malnutrition and inflammation may similarly suppress the production of TTR through distinct and unrelated pathophysiological mechanisms while operating in concert to downsize LBM stores. The hepatic synthesis of TTR integrates both machineries, acting as a marker of reduced LBM resources still available for defense and repair processes. TTR operates as a universal surrogate analyte that allows for the grading of residual LBM capacity to reflect disease burden. Measurement of TTR is a simple, rapid, and inexpensive micro-method that may be reproduced on a daily basis, hence ideally suited for the follow-up of the most intricated clinical situations and as a reliable predictor of any morbidity outcome.
Topics: Biomarkers; Humans; Inflammation; Liver; Prealbumin
PubMed: 35943703
DOI: 10.1007/s11684-022-0940-3 -
Journal of the American Heart... Apr 2022Advancement in the diagnosis and treatment of transthyretin amyloid cardiomyopathy has made great strides in recent years. Novel therapeutics for transthyretin... (Review)
Review
Advancement in the diagnosis and treatment of transthyretin amyloid cardiomyopathy has made great strides in recent years. Novel therapeutics for transthyretin amyloidosis such as tafamidis, patisiran, and inotersen have shown significant benefits in a not-so-rare disease but come with high listing price tags ranging from a quarter to more than a half million dollars per year. These costs create significant financial barriers for the majority of patients, especially those with existing Medicare insurance plans. Of 72 patients reviewed, 67% were Medicare beneficiaries. Financial assistance was explored for the majority, and 37 (51%) patients with Medicare Part D received financial assistance that reduced their copayments to $0. Only one-third of our patients were able to afford these medications without any forms of financial assistance. Of these patients, 4 (6%) had the highest copayments ranging from $13 000 to $15 000 per year. To navigate the complexities of prescribing and affordability in amyloidosis, a multidisciplinary team including a dedicated clinical pharmacist is crucial in guaranteeing patients' success to secure these novel therapeutics. In this article, we discuss our experiences with prescribing, acquiring insurance authorizations, and financing these life-saving medications based on patient-specific insurance plans and socioeconomic status.
Topics: Aged; Amyloid Neuropathies, Familial; Humans; Medicare; Prealbumin; United States
PubMed: 35301856
DOI: 10.1161/JAHA.121.023895 -
Progress in Cardiovascular Diseases 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underrecognized cause of heart failure (HF). ATTR-CM can lead to a number of cardiovascular manifestations including... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underrecognized cause of heart failure (HF). ATTR-CM can lead to a number of cardiovascular manifestations including HF, rhythm disturbances, and valvular disease that ultimately limit quality of life and prognosis. Due to advances in diagnostic modalities and therapeutic options, the prevalence of ATTR-CM is rising. There are several classes of medications under active investigation, though most therapies are most efficacious if instituted early on in the disease course. As such, early clinical recognition and prompt diagnosis are crucial to improving disease related outcomes. In this review, we highlight clinical manifestations of ATTR-CM as well as contemporary diagnostic and treatment approaches to the disease.
Topics: Humans; Cardiomyopathies; Prealbumin; Amyloid Neuropathies, Familial; Quality of Life; Heart Failure
PubMed: 38246305
DOI: 10.1016/j.pcad.2024.01.013 -
International Journal of Cardiology Mar 2024
Topics: Humans; Amyloid Neuropathies, Familial; Electrocardiography; Prealbumin
PubMed: 37852541
DOI: 10.1016/j.ijcard.2023.131442 -
International Journal of Molecular... Dec 2019Preeclampsia (PE) is a multisystem heterogeneous complication of pregnancy remaining a leading cause of maternal and perinatal morbidity and mortality over the world. PE... (Review)
Review
Preeclampsia (PE) is a multisystem heterogeneous complication of pregnancy remaining a leading cause of maternal and perinatal morbidity and mortality over the world. PE has a large spectrum of clinical features and symptoms, which make diagnosis challenging. Despite a long period of studying, PE etiology is still unclear and there are no reliable rapid tests for early diagnosis of this disease. During the last decade, it was shown that proteins misfolding and aggregation are associated with PE. Several proteins, including amyloid beta peptide, transthyretin, alpha-1 antitrypsin, albumin, IgG k-free light chains, and ceruloplasmin are dysregulated in PE, resulting in toxic deposition of amyloid-like aggregates in the placenta and body fluids. It is also possible that aggregated proteins induce defective trophoblast invasion, placental ischemia, ER stress, and promote PE manifestation. The fact that protein aggregation is an emerging biomarker of PE provides an opportunity to develop new diagnostic approaches based on amyloids special features, such as Congo red (CR) staining and thioflavin T (ThT) enhanced fluorescence.
Topics: Amyloid; Benzothiazoles; Biomarkers; Female; Humans; Placenta; Pre-Eclampsia; Prealbumin; Pregnancy; Protein Aggregation, Pathological; Protein Folding
PubMed: 31817906
DOI: 10.3390/ijms20246183 -
Revista de Investigacion Clinica;... 2021Transthyretin (TTR) amyloidosis (ATTR) is a progressive condition characterized by multiorgan accumulation of amyloid deposits composed of transthyretin (TTR) fibrils....
Transthyretin (TTR) amyloidosis (ATTR) is a progressive condition characterized by multiorgan accumulation of amyloid deposits composed of transthyretin (TTR) fibrils. Over the past decades, despite being a rare disease, ATTR amyloidosis has enabled top-tier therapeutics. In the 90s, organ transplantation was the mainstream therapeutic option and fostered distinct approaches, such as combined liver-heart transplant and domino (sequential) liver transplantation. Likewise, several TTR molecule stabilizers were developed successfully. Over the past decade, oriented genetic therapies emerged to prevent, control, and, surprisingly, reverse amyloid deposition. Silencing the TTR gene using different strategies is flourishing, and ongoing trials continue to evaluate diverse approaches to optimize their application. The following perspective describes the currently available treatments for ATTR amyloidosis and the prospects on the potential application of these strategies in other medical fields.
Topics: Amyloid Neuropathies, Familial; Humans; Liver; Prealbumin
PubMed: 34609369
DOI: 10.24875/RIC.21000323 -
Frontiers in Cellular and Infection... 2024The primary aim of this study is to investigate the correlation between serum levels of fibrinogen-to-prealbumin ratio (FPR) and C-reactive protein-to-prealbumin ratio...
BACKGROUND
The primary aim of this study is to investigate the correlation between serum levels of fibrinogen-to-prealbumin ratio (FPR) and C-reactive protein-to-prealbumin ratio (CPR) and prognostic outcomes among patients with severe fever with thrombocytopenia syndrome (SFTS). SFTS, characterized by elevated mortality rates, represents a substantial public health challenge as an emerging infectious disease.
METHODS
The study included 159 patients with SFTS. Clinical and laboratory data were compared between the survival and death groups. Univariate and multivariate logistic regression analysis were utilized to identify independent risk factors for mortality. The predictive efficacy of FPR and CPR was evaluated using receiver operating characteristic (ROC) curve. Survival analysis was conducted using the Kaplan-Meier curve and the log-rank test was employed for comparison.
RESULTS
The death group exhibited significantly elevated levels of FPR and CPR compared to the survival group ( < 0.05). Multivariate logistic regression analysis confirmed that both FPR and CPR independently correlated with a poorer prognosis among patients with SFTS. The ROC curve analysis indicated that FPR and CPR had superior predictive capabilities compared to C-reactive protein and fibrinogen. Kaplan-Meier survival analysis demonstrated that patients with SFTS who have FPR > 0.045 (log-rank test; χ2 = 17.370, < 0.001) or CPR > 0.05 (log-rank test; χ2 = 19.442, < 0.001) experienced significantly lower survival rates within a 30-day follow-up period.
CONCLUSION
Elevated levels of FPR and CPR serve as distinct risk factors for mortality among patients with SFTS, indicating their potential to predict an unfavorable prognosis in these patients.
Topics: Humans; C-Reactive Protein; Male; Female; Fibrinogen; Prognosis; Middle Aged; Aged; Severe Fever with Thrombocytopenia Syndrome; ROC Curve; Prealbumin; Biomarkers; Risk Factors; Adult; Phlebovirus; Kaplan-Meier Estimate; Retrospective Studies
PubMed: 38915920
DOI: 10.3389/fcimb.2024.1397789 -
Drug Design, Development and Therapy 2020Transthyretin (TTR) is a tetrameric protein, and its dissociation, aggregation, deposition, and misfolding are linked to several human amyloid diseases. As the main... (Review)
Review
Transthyretin (TTR) is a tetrameric protein, and its dissociation, aggregation, deposition, and misfolding are linked to several human amyloid diseases. As the main transporter for thyroxine (T4) in plasma and cerebrospinal fluid, TTR contains two T4-binding sites, which are docked with T4 and subsequently maintain the structural stability of TTR homotetramer. Affected by genetic disorders and detrimental environmental factors, TTR degrades to monomer and/or form amyloid fibrils. Reasonably, stabilization of TTR might be an efficient strategy for the treatment of TTR-related amyloidosis. However, only 10-25% of T4 in the plasma is bound to TTR under physiological conditions. Expectedly, T4 analogs with different structures aiming to bind to T4 pockets may displace the functions of T4. So far, a number of compounds including both natural and synthetic origin have been reported. In this paper, we summarized the potent inhibitors, including bisaryl structure-based compounds, flavonoids, crown ethers, and carboranes, for treating TTR-related amyloid diseases and the combination modes of some compounds binding to TTR protein.
Topics: Amyloid; Amyloidosis; Humans; Models, Molecular; Molecular Structure; Prealbumin
PubMed: 32210536
DOI: 10.2147/DDDT.S237252 -
Neurology May 2023Hereditary transthyretin amyloidosis (hATTR) is a rare autosomal dominant systemic disease with variable penetrance and heterogeneous clinical presentation. Several...
BACKGROUND AND OBJECTIVES
Hereditary transthyretin amyloidosis (hATTR) is a rare autosomal dominant systemic disease with variable penetrance and heterogeneous clinical presentation. Several effective treatments can reduce mortality and disability, though diagnosis remains challenging, especially in the United States where disease is nonendemic. Our aim is to describe the neurologic and cardiac characteristics of common US ATTR variants V122I, L58H, and late-onset V30M at presentation.
METHODS
We conducted a retrospective case series of patients with a new diagnosis of ATTRv between January 2008 and January 2020 to characterize features of prominent US variants. The neurologic (examination, EMG, and skin biopsy), cardiac (echo), and laboratory assessments (pro b-type natriuretic peptide [proBNP] and reversible neuropathy screens) are described.
RESULTS
A total of 56 patients with treatment-naïve ATTRv with symptoms/signs of peripheral neuropathy (PN) or cardiomyopathy and confirmatory genetic testing presenting with Val122Ile (N = 31), late-onset Val30Met (N = 12), and Leu58His ATTRv (N = 13) were included. The age at onset and sex distributions were similar (V122I: 71.5 ± 8.0, V30M: 64.8 ± 2.6, and L58H: 62.4 ± 9.8 years; 26, 25, 31% female). Only 10% of patients with V122I and 17% of patients with V30M were aware of an ATTRv family history, while 69% of patients with L58H were aware. PN was present in all 3 variants at diagnosis (90%, 100%, and 100%), though neurologic impairment scores differed: V122I: 22 ± 16, V30M: 61 ± 31, and L58H: 57 ± 25. Most points (deficits) were attributed to loss of strength. Carpal tunnel syndrome (CTS) and a positive Romberg sign were common across all groups (V122I: 97%, 39%; V30M: 58%, 58%; and L58H: 77%, 77%). ProBNP levels and interventricular septum thickness were highest among patients with V122I (5,939 ± 962 pg/mL, 1.70 ± 0.29 cm), followed by V30M (796 ± 970 pg/mL, 1.42 ± 0.38 cm) and L58H (404 ± 677 pg/mL, 1.23 ± 0.36 cm). Atrial fibrillation was present among 39% of cases with V122I and only 8% of cases with V30M and L58H. Gastrointestinal symptoms were rare (6%) among patients with V122I and common in patients with V30M (42%) and L58H (54%).
DISCUSSION
Important clinical differences exist between ATTRv genotypes. While V122I is perceived to be a cardiac disease, PN is common and clinically relevant. Most patients with V30M and V122I were diagnosed de novo and therefore require clinical suspicion for diagnosis. A history of CTS and a positive Romberg sign are helpful diagnostic clues.
Topics: Female; Male; Humans; Retrospective Studies; Amyloid Neuropathies, Familial; Cardiomyopathies; Phenotype; Prealbumin
PubMed: 36941075
DOI: 10.1212/WNL.0000000000207158 -
European Journal of Heart Failure Feb 2021Amyloidoses are characterized by the tissue accumulation of misfolded proteins into insoluble fibrils. The two most common types of systemic amyloidosis result from the... (Review)
Review
Amyloidoses are characterized by the tissue accumulation of misfolded proteins into insoluble fibrils. The two most common types of systemic amyloidosis result from the deposition of immunoglobulin light chains (AL) and wild-type or variant transthyretin (ATTRwt/ATTRv). Cardiac involvement is the main determinant of outcome in both AL and ATTR, and cardiac amyloidosis (CA) is increasingly recognized as a cause of heart failure. In CA, circulating biomarkers are important diagnostic tools, allow to refine risk stratification at baseline and during follow-up, help to tailor the therapeutic strategy and monitor the response to treatment. Among amyloid precursors, free light chains are established biomarkers in AL amyloidosis, while the plasma transthyretin assay is currently being investigated as a tool for supporting the diagnosis of ATTRv amyloidosis, predicting outcome and monitor response to novel tetramer stabilizers or small interfering RNA drugs in ATTR CA. Natriuretic peptides (NPs) and troponins are consistently elevated in patients with AL and ATTR CA. Plasma NPs, troponins and free light chains hold prognostic significance in AL amyloidosis, and are evaluated for therapy decision-making and follow-up, while the value of NPs and troponins in ATTR is less well established. Biomarkers can be usefully integrated with clinical and imaging variables at all levels of the clinical algorithm of systemic amyloidosis, from screening to diagnosis and prognosis, and treatment tailoring.
Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Heart Failure; Humans; Prealbumin
PubMed: 33527656
DOI: 10.1002/ejhf.2113