-
Kidney International Mar 2015Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases... (Review)
Review
Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the precursor protein, inhibitors of fibrillogenesis, fibril disruptors, and blockers of protein translation, transcription, and immunotherapy. We review many of these approaches that are currently being assessed in clinical trials.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Humans; Immunoglobulin Light Chains; Immunotherapy; Kidney Transplantation; Molecular Targeted Therapy; Prealbumin; Serum Amyloid A Protein; Stem Cell Transplantation
PubMed: 25469850
DOI: 10.1038/ki.2014.368 -
ESC Heart Failure Oct 2021Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial...
AIMS
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder that remains underdiagnosed. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) was the first large clinical trial to include both wild-type (ATTRwt) and hereditary (ATTRv) patients. A description of the natural history of ATTR-CM, utilizing data from placebo-treated patients in ATTR-ACT, will provide a greater understanding of presentation and progression of ATTR-CM and may aid in disease awareness, earlier diagnosis and treatment monitoring.
METHODS AND RESULTS
Changes in clinical endpoints (mortality, cardiovascular [CV]-related hospitalizations, 6-min walk test [6MWT] distance and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) from baseline to Month 30 in the 177 patients (134 ATTRwt, 43 ATTRv) who received placebo in ATTR-ACT were assessed. ATTRwt patients tended to have less severe disease at baseline. Over the duration of ATTR-ACT, there were 76 (42.9%) all-cause deaths, and 107 (60.5%) patients had a CV-related hospitalization. There was a lower proportion of all-cause deaths in ATTRwt (49, 36.6%) than ATTRv (27, 62.8%). There was a similar, steady decline in mean (SD) 6MWT distance from baseline to Month 30 in ATTRwt (93.9 [93.7] m) and ATTRv (89.1 [107.2] m) patients. The decline in mean (SD) KCCQ-OS score was less severe in ATTRwt (13.8 [20.7]) than ATTRv (21.0 [26.4]) patients.
CONCLUSIONS
Patients with ATTR-CM experience a severe, progressive disease. In ATTR-ACT, placebo-treated patients with ATTRv, compared with ATTRwt, had more severe disease at baseline, and their disease progressed more rapidly as shown by mortality, hospitalizations and quality of life over time.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Hospitalization; Humans; Prealbumin; Quality of Life
PubMed: 34432383
DOI: 10.1002/ehf2.13541 -
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 -
Journal of the American Heart... Aug 2023
Topics: Humans; Aged; Prealbumin; Penetrance; Amyloidosis; Heart Failure; Health Disparate Minority and Vulnerable Populations
PubMed: 37486081
DOI: 10.1161/JAHA.123.030802 -
Medicine Oct 2021We designed this study to assess the effectiveness of prealbumin as an indicator of growth as well as a nutritional marker in neonates.Between March 2017 and June 2019,...
We designed this study to assess the effectiveness of prealbumin as an indicator of growth as well as a nutritional marker in neonates.Between March 2017 and June 2019, we measured serum prealbumin concentrations of 80 neonates in neonatal intensive care unit at birth, postnatal day 14 and 28, and classified them into 3 groups (early preterm, late preterm, and term infants). And we examined correlation among prealbumin levels, nutritional intake, and anthropometric measurements (weight, length, and head circumference) in neonates.Prealbumin measured on the 14th postnatal day in early preterm infants showed significant correlations with the length, weight, and head circumference z-scores. Prealbumin levels increased with time in the late preterm and term groups. At birth, prealbumin levels were the lowest in late preterm babies, implying that they are nutritionally deficient and need nutritional support. At postnatal day 28, the prealbumin levels of many preterm infants did not reach those seen in term babies at birth, suggesting the presence of extrauterine growth restriction.Prealbumin can be considered as an indicator of sufficient growth in early preterm infants.
Topics: Biomarkers; Body Weights and Measures; C-Reactive Protein; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Prealbumin; Retrospective Studies; Sex Factors
PubMed: 34678912
DOI: 10.1097/MD.0000000000027603 -
Medicina 2020
Topics: Amyloid Neuropathies, Familial; Heart; Humans; Prealbumin
PubMed: 32841141
DOI: No ID Found -
International Journal of Molecular... Apr 2021Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In... (Review)
Review
Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In addition, this protein is infamous for its amyloidogenic propensity, causing various amyloidoses in humans, such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. It has been known for over two decades that decreased stability of the native tetrameric conformation of TTR is the main cause of these diseases. Yet, mechanistic details on the amyloidogenic transformation of TTR were not clear until recent multidisciplinary investigations on various structural states of TTR. In this review, we discuss recent advancements in the structural understanding of TTR misfolding and amyloidosis processes. Special emphasis has been laid on the observations of novel structural features in various amyloidogenic species of TTR. In addition, proteolysis-induced fragmentation of TTR, a recently proposed mechanism facilitating TTR amyloidosis, has been discussed in light of its structural consequences and relevance to acknowledge the amyloidogenicity of TTR.
Topics: Amyloid; Amyloid Neuropathies, Familial; Animals; Humans; Prealbumin; Protein Folding
PubMed: 33922648
DOI: 10.3390/ijms22094429 -
International Journal of Molecular... Dec 2022The care of systemic amyloidosis has improved dramatically due to improved awareness, accurate diagnostic tools, the development of powerful prognostic and companion... (Review)
Review
The care of systemic amyloidosis has improved dramatically due to improved awareness, accurate diagnostic tools, the development of powerful prognostic and companion biomarkers, and a continuous flow of innovative drugs, which translated into the blooming of phase 2/3 interventional studies for light chain (AL) and transthyretin (ATTR) amyloidosis. The unprecedented availability of effective drugs ignited great interest across various medical specialties, particularly among cardiologists who are now recognizing cardiac amyloidosis at an extraordinary pace. In all amyloidosis referral centers, we are observing a substantial increase in the prevalence of wild-type transthyretin (ATTRwt) cardiomyopathy, which is now becoming the most common form of cardiac amyloidosis. This review focuses on the oral drugs that have been recently introduced for the treatment of ATTR cardiac amyloidosis, for their ease of use in the clinic. They include both old repurposed drugs or fit-for-purpose designed compounds which bind and stabilize the TTR tetramer, thus reducing the formation of new amyloid fibrils, such as tafamidis, diflunisal, and acoramidis, as well as fibril disruptors which have the potential to promote the clearance of amyloid deposits, such as doxycycline. The development of novel therapies is based on the advances in the understanding of the molecular events underlying amyloid cardiomyopathy.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Diflunisal; Cardiomyopathies; Amyloid
PubMed: 36555787
DOI: 10.3390/ijms232416145 -
European Journal of Heart Failure Jun 2023Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is...
AIM
Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival.
METHODS AND RESULTS
This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival.
CONCLUSIONS
Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.
Topics: Humans; Prealbumin; Amyloid Neuropathies, Familial; Retrospective Studies; Heart Failure; Cardiomyopathies
PubMed: 36907828
DOI: 10.1002/ejhf.2823 -
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