Abstract
Congenital fibrinogen disorders (CFDs) encompass a heterogeneous group of fibrinogen defects with a wide spectrum of biological and clinical features. An accurate diagnosis is thus essential ...to assure the optimal management for the patient. Diagnosis involves a multistep approach starting with routine coagulation assays and assessment of functional and antigenic fibrinogen followed by identification of the molecular anomaly. However, the diagnosis of CFD can be challenging as the sensitivity and specificity of coagulation assays depend on the fibrinogen level as well as on the fibrinogen variant. In addition, patients suffering from CFD have a heterogeneous clinical course which is often unpredictable by routine coagulation assays. To better determine the patient's clinical phenotype, global hemostasis assays and an assessment of the fibrin clot properties are performed in research laboratories. In this review, we summarize the fibrinogen work-up highlighting some common pitfalls and provide an update of the research on CFD.
How I treat dysfibrinogenemia Casini, Alessandro; de Moerloose, Philippe
Blood,
11/2021, Volume:
138, Issue:
21
Journal Article
Peer reviewed
Open access
Congenital dysfibrinogenemia (CD) is caused by structural changes in fibrinogen that modify its function. Diagnosis is based on discrepancy between decreased fibrinogen activity and normal fibrinogen ...antigen levels and is confirmed by genetic testing. CD is caused by monoallelic mutations in fibrinogen genes that lead to clinically heterogenous disorders. Most patients with CD are asymptomatic at the time of diagnosis, but the clinical course may be complicated by a tendency toward bleeding and/or thrombosis. Patients with a thrombosis-related fibrinogen variant are particularly at risk, and, in such patients, long-term anticoagulation should be considered. Management of surgery and pregnancy raise important and difficult issues. The mainstay of CD treatment remains fibrinogen supplementation. Antifibrinolytic agents are part of the treatment in some specific clinical settings. In this article, we discuss 5 clinical scenarios to highlight common clinical challenges. We detail our approach to establishing a diagnosis of CD and discuss strategies for the management of bleeding, thrombosis, surgery, and pregnancy.
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Hereditary fibrinogen disorders (HFDs) are rare bleeding disorders with a wide spectrum of biological and clinical features. While most patients with HFDs are at risk to suffer from mild to severe, ...sometimes life-threatening bleeding, thrombotic events are also common. Therefore, an appropriate diagnosis is needed to offer the optimal treatment. Diagnosis of HFDs can be challenging and plenty of pitfalls. The sensitivity and specificity of hemostasis routine test are depending on the reagents, the methods, and the fibrinogen variants. To distinguish subtypes of HFDs additional tests are often required. Historically based on the assessment of fibrinogen levels, a recent classification also considers the clinical phenotype and the genotype. In this short review, diagnosis strategies and HFDs classification are reviewed.
The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes.
We aimed to update our previous meta-analysis of published cohort ...prospective studies that investigated the effects of adherence to the Mediterranean diet on health status.
We conducted a comprehensive literature search through electronic databases up to June 2010.
The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality relative risk (RR) = 0.92; 95% CI: 0.90, 0.94, cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality.
This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.
To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for ...proposing a literature-based adherence score to the Mediterranean diet.
We conducted a comprehensive literature search through all electronic databases up to June 2013.
Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained.
The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses.
A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet.
The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.
Building upon the continuous record asymptotic framework recently introduced by Casini and Perron (2020a) for inference in structural change models, we propose a Laplace-based (Quasi-Bayes) procedure ...for the construction of the estimate and confidence set for the date of a structural change. It is defined by an integration rather than an optimization-based method. A transformation of the least-squares criterion function is evaluated in order to derive a proper distribution, referred to as the Quasi-posterior. For a given choice of a loss function, the Laplace-type estimator is the minimizer of the expected risk with the expectation taken under the Quasi-posterior. Besides providing an alternative estimate that is more precise—lower mean absolute error (MAE) and lower root-mean squared error (RMSE)—than the usual least-squares one, the Quasi-posterior distribution can be used to construct asymptotically valid inference using the concept of Highest Density Region. The resulting Laplace-based inferential procedure is shown to have lower MAE and RMSE, and the confidence sets strike a better balance between empirical coverage rates and average lengths of the confidence sets relative to traditional long-span methods, whether the break size is small or large.
Purpose
We evaluated the effect of low-calorie mediterranean (MD) and vegetarian (VD) diets on gut microbiome (GM) composition and short-chain-fatty acids (SCFA) production.
Methods
We performed next ...generation sequencing (NGS) of 16S rRNA and SCFA analysis on fecal samples of 23 overweight omnivores (16 F; 7 M) with low-to-moderate cardiovascular risk. They were randomly assigned to a VD or MD, each lasting 3 months, with a crossover study design.
Results
Dietary interventions did not produce significant diversity in the GM composition at higher ranks (family and above), neither between nor within MD and VD, but they did it at genus level. MD significantly changed the abundance of
Enterorhabdus
,
Lachnoclostridium
and
Parabacteroides
, while VD significantly affected the abundance of
Anaerostipes
,
Streptococcus
,
Clostridium
sensu stricto, and
Odoribacter
. Comparison of the mean variation of each SCFA between MD and VD showed an opposite and statistically significant trend for propionic acid (+ 10% vs − 28%, respectively,
p
= 0.034). In addition, variations of SCFA were negatively correlated with changes of some inflammatory cytokines such as VEGF, MCP-1, IL-17, IP-10 and IL-12, only after MD. Finally, correlation analyses showed a potential relationship—modulated by the two diets—between changes of genera and changes of clinical and biochemical parameters.
Conclusions
A short-term dietary intervention with MD or VD does not induce major change in the GM, suggesting that a diet should last longer than 3 months for scratching the microbial resilience. Changes in SCFA production support their role in modulating the inflammatory response, thus mediating the anti-inflammatory and protective properties of MD.
The study of inherited fibrinogen disorders, characterized by extensive allelic heterogeneity, allows the association of defined mutations with specific defects providing significant insight into the ...location of functionally important sites in fibrinogen and fibrin. Since the identification of the first causative mutation for congenital afibrinogenemia, studies have elucidated the underlying molecular pathophysiology of numerous causative mutations leading to fibrinogen deficiency, developed cell-based and animal models to study human fibrinogen disorders, and further explored the clinical consequences of absent, low, or dysfunctional fibrinogen. Since qualitative disorders are addressed by another review in this special issue, this review will focus on quantitative disorders and will discuss their diagnosis, clinical features, molecular bases, and introduce new models to study the phenotypic consequences of fibrinogen deficiency.
Fibrinogen is an abundant protein synthesized in the liver, present in human blood plasma at concentrations ranging from 1.5-4 g/L in healthy individuals with a normal half-life of 3-5 days. With ...fibrin, produced by thrombin-mediated cleavage, fibrinogen plays important roles in many physiological processes. Indeed, the formation of a stable blood clot, containing polymerized and cross-linked fibrin, is crucial to prevent blood loss and drive wound healing upon vascular injury. A balance between clotting, notably the conversion of fibrinogen to fibrin, and fibrinolysis, the proteolytic degradation of the fibrin mesh, is essential. Disruption of this equilibrium can cause disease in distinct manners. While some pathological conditions are the consequence of altered levels of fibrinogen, others are related to structural properties of the molecule. The source of fibrinogen expression and the localization of fibrin(ogen) protein also have clinical implications. Low levels of fibrinogen expression have been detected in extra-hepatic tissues, including carcinomas, potentially contributing to disease. Fibrin(ogen) deposits at aberrant sites including the central nervous system or kidney, can also be pathological. In this review, we discuss disorders in which fibrinogen and fibrin are implicated, highlighting mechanisms that may contribute to disease.
The mechanisms allowing the cellular transport of ascorbic acid represent a primary aspect for the understanding of the roles played by this vitamin in pathophysiology. Considerable research effort ...has been spent in the field, on several animal models and different cell types. Several mechanisms have been described to date, mediating the movements of different redox forms of ascorbic acid across cell membranes. Vitamin C can enter cells both in its reduced and oxidized form, ascorbic acid (AA) and dehydroascorbate (DHA), utilizing respectively sodium-dependent transporters (SVCT) or glucose transporters (GLUT). Modulation of SVCT expression and function has been described by cytokines, steroids and post-translational protein modification. Cellular uptake of DHA is followed by its intracellular reduction to AA by several enzymatic and non-enzymatic systems. Efflux of vitamin C has been also described in a number of cell types and different pathophysiological functions were proposed for this phenomenon, in dependence of the cell model studied. Cellular efflux of AA is mediated through volume-sensitive (VSOAC) and Ca
2+-dependent anion channels, gap-junction hemichannels, exocytosis of secretory vesicles and possibly through homo- and hetero-exchange systems at the plasma membrane level. Altogether, available data suggest that cellular efflux of ascorbic acid – besides its uptake – should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin.
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