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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 -
World Journal of Surgical Oncology Jan 2020Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with... (Review)
Review
OBJECTIVE
Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with cancer.
MATERIALS AND METHODS
Four databases (PubMed, Web of Science, Cochrane Library, and WanFang) were searched. The primary endpoints were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Pooled data were synthesized using StataMP 14 and expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
This update examined 19 studies (7282 cases) that assessed the correlation of AFR with cancer prognosis. Pooled univariate and multivariate analyses indicated significant correlations of low AFR with poor OS (HR 2.18, 95%CI 1.87-2.55 and HR 1.75, 95%CI 1.54-2.00, respectively), poor DFS (HR 1.89, 95%CI 1.54-2.32 and HR 1.51, 95%CI 1.29-1.76, respectively), and poor PFS (HR 1.68, 95%CI 1.42-1.99 and HR 1.48, 95%CI 1.16-1.88, respectively). Pooled univariate and multivariate analyses of 6 studies (2232 cases) indicated high FPR significantly correlated with poor OS (HR 2.37, 95%CI 2.03-2.77 and HR 1.97, 95%CI 1.41-2.77, respectively). One study reported that high FPR correlated with poor DFS (univariate analysis: HR 2.20, 95%CI 1.35-3.57; multivariate analysis: HR 1.77, 95%CI 1.04-2.99) and one study reported a correlation of high FPR with poor PFS in univariate analysis alone (HR 1.79, 95%CI 1.11-2.88).
CONCLUSION
A low AFR and a high FPR correlated with increased risk of cancer mortality and recurrence. AFR and FPR may be promising prognostic markers for cancers.
Topics: Albumins; Biomarkers, Tumor; Fibrinogen; Humans; Neoplasms; Prealbumin; Prognosis
PubMed: 31931816
DOI: 10.1186/s12957-020-1786-2 -
Acta Neuropathologica Jan 2023Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset...
Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27-69 years and with a mean disease duration of 10.9 years (range: 3-29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.
Topics: Adult; Humans; Prealbumin; Amyloid Neuropathies, Familial; Nervous System Diseases; Mutation; Brain
PubMed: 36198883
DOI: 10.1007/s00401-022-02501-9 -
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 -
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