La importancia de la genética en el estudio de la hipertrigliceridemia / The importance of genetics in the study of hypertriglyceridemia

La hipertrigliceridemia engloba un conjunto de trastornos lipídicos comunes en la práctica clínica, generalmente definidos como una concentración superior a 150mg/dL en ayunas. Existen diversas clasificaciones de la gravedad de la hipertrigliceridemia en función de sus valores séricos, considerándose por norma general moderada cuando los niveles son inferiores a 500mg/dL y severa cuando son mayores de 1.000mg/dL. Su importancia radica en su asociación con otras alteraciones del perfil lipídico, contribuyendo al aumento del riesgo cardiovascular y de pancreatitis aguda, fundamentalmente con concentraciones superiores a 500mg/dL.(AU)

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.(AU)

[The importance of genetics in the study of hypertriglyceridemia]. / La importancia de la genética en el estudio de la hipertrigliceridemia.

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.

Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

OBJECTIVES: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. METHODS: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. RESULTS: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. CONCLUSIONS: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).

COVID-19 vaccines should be evaluated from the societal perspective.

The COVID-19 pandemic demonstrates the importance of valuing vaccines from a broad societal perspective (SP), as opposed to a narrower health-payer perspective (HPP). COVID-19's catastrophic global impacts extend not only to its health-related effects, but also to the profound macroeconomic losses caused by lockdowns required for disease control, leading to the worst global economic crisis in a century. COVID-19 vaccination (CV) has been the central policy tool for resolving this economic crisis, and it has been hypothesized that this macroeconomic benefit alone justifies the cost of CV many times over. Yet HPP-based vaccine valuations are wholly insensitive to this enormous benefit, not allowing it to influence the allocation of given health budgets nor the determination of the magnitudes of such budgets, thereby risking inadequate societal spending on CV. HPP allocates given health budgets to maximize only health, giving no weight to macroeconomic outcomes, causing allocative inefficiency by not allowing welfare-improving trade-offs of health for wealth. HPP assumes health budgets are optimal, not scrutinizing whether their scale adequately reflects the macroeconomic benefits of health spending, thereby risking productive inefficiency by foregoing health spending increases such as on CV that could raise both population-level health and wealth. These allocative and productive inefficiencies in turn distort for-profit R&D incentives, risking dynamic inefficiency. And since the socio-economic and health burdens of COVID-19 are disproportionately borne by the worse off, HPP's failure to promote optimal levels of societal investment in CV may disproportionately burden the worse off as well, exacerbating inequality. Vaccine valuations from the societal perspective allow the allocation and determination of health budgets to reflect macroeconomic and distributional values, thereby promoting allocative, productive, and dynamic efficiency, as well as equity. These considerations of efficiency and equity support evaluating CV, and to ensure a level playing field, all vaccines, from a societal perspective.

Immunization, not vaccination: monoclonal antibodies for infant RSV prevention and the US vaccines for children program.

In the US, RSV imposes significant burdens on infants, households, and the health system. Yet the only licensed immunization is accessible to only certain risk groups comprising 2% of the infant population, leaving the remaining 98% unprotected. An effective immunization for all infants is a significant public health priority. One possible solution is the FDA-approved monoclonal antibody nirsevimab, which recent evidence suggests is safe and effective in preventing RSV in all infants, and which is currently being considered for inclusion in the pediatric immunization schedule and the federal Vaccines for Children (VFC) program. But the question arises whether passive immunization products like nirsevimab ought to be eligible for the VFC, which nominally and traditionally centers on vaccines providing active immunity. Addressing this is urgent because VFC inclusion will be decided on imminently. I argue there are strong policy grounds, i.e., reasons grounded in the ultimate health system goals of maximizing population health or social welfare subject to resource constraints, not to exclude passive immunization from VFC eligibility. Active and passive immunizations both provide adaptive immunity and can therefore produce qualitatively similar effects on risks of infection, disease, and transmission; on disease severity and duration; and on health, welfare, and health resource use. The distinction between active and passive immunization does not intrinsically matter since what matters for the attainment of health system goals is the extent of immunity conferred, not whether immunity is active or passive. Nor can passivity be considered a useful proxy for conferring a lesser extent of immunity, since no such proxy is needed (existing valuation methods can cope with variations in product attributes), and it is a poor proxy (passive immunizations can be better for individuals with impaired immune systems and can have comparable effectiveness durations and economic value as vaccines).

Cost-utility and cost-benefit analysis of pediatric PCV programs in Egypt.

New vaccine introductions (NVIs) raise issues of value for money (VfM) for self-financing middle-income countries like Egypt. We evaluate a pediatric pneumococcal conjugate vaccine (PCV) NVI in Egypt from health payer and societal perspectives, using cost-utility and cost-benefit analysis (CUA, CBA). We evaluate vaccinating 100 successive birth cohorts with the 13-valent PCV ("PCV13") and the 10-valent PCV ("PCV10") relative to no vaccination and each other. We quantify health effects with a disease incidence projection model and a multiple-cohort static disease model. Our CBA uses a health-augmented lifecycle model to generate willingness-to-pay for health gains from which we calculate rates of return (RoR). We obtain parameters from the published literature. We perform deterministic and probabilistic sensitivity analysis. Our base-case CUA finds incremental cost-effectiveness ratios (ICERs) for PCV13 and PCV10 relative to no program of $926 (95% confidence interval $512-$1,735) and $1,984 ($1,186-$3,805) per quality-adjusted life year (QALY), respectively; and for PCV13 relative to PCV10 of $174 ($88-$331) per QALY. Our base-case CBA finds RoRs to PCV13 and PCV10 relative to no program of 488% (188-993%) and 164% (33-336%), respectively, and to PCV13 relative to PCV10 of 3109% (1410-6602%). Both CUA and CBA find PCV13 to be good VfM relative to PCV10.

The value of vaccines.

Optimizing vaccine spending depends on recognizing the full value of vaccination (VoV). Existing taxonomies of such value are not comprehensive because they are not guided by general theories. I rely on two such theories: subjective-value theory claims that what has value is determined by what people actually or ideally want in life. A welfarist theory of government states that a fundamental objective of government is to promote social value (or social welfare). These jointly imply that any aspect of life that individuals actually or ideally value and that could be negatively affected by vaccine-preventable diseases (and therefore positively affected by preventive vaccines) is an element of VoV. I build a more comprehensive-value taxonomy than currently exists based on this implication.

Cost-utility and cost-benefit analysis of TAVR availability in the US severe symptomatic aortic stenosis patient population.

AIMS: We evaluated the availability of transcatheter aortic valve replacement (TAVR) to determine its value across all severe symptomatic aortic stenosis (SSAS) patients, especially those untreated because of concerns regarding invasive surgical AVR (SAVR) and its impact on active aging. METHODS: We performed payer perspective cost-utility analysis (CUA) and societal perspective cost-benefit analysis (CBA). The CBA's benefit measure is active time: salaried labor, unpaid work, and active leisure. The study population is a cohort of US elderly SSAS patients. We compared a "TAVR available" scenario in which SSAS patients distribute themselves across TAVR, SAVR, and medical management (MM); and a "TAVR not available" scenario with only SAVR and MM. We structured each scenario with a decision-tree model of SSAS patient treatment allocation. We measured the association between health and active time in the US Health and Retirement Study and used this association to impute active time to SSAS patients given their health. RESULTS: The incremental cost-effectiveness ratio (ICER) and rate of return (RoR) of TAVR availability were $8,533 and 395%, respectively. CUA net monetary benefits (NMB) were $212,199 per patient and $43.4 billion population-wide. CBA NMB were $50,530 per patient and $10.3 billion population-wide. LIMITATIONS: Among study limitations were scarcity of evidence regarding key parameters and the lack of long-term survival, health utility, and treatment cost data. Our analysis did not account for TAVR durability, retreatments, and valve-in-valve treatments. CONCLUSION: Across risk-, age-, and treatment-eligibility groups, TAVR is the economically optimal treatment choice. It represents strong value-for-money per patient and population-wide. The vast majority of TAVR value involves raising treatment uptake among the untreated.

Aortic stenosis (AS) is a common and lethal heart disease. Surgical treatment has long been available, but its invasiveness limits uptake. More recently, transcatheter aortic valve replacement (TAVR) has emerged as a treatment alternative. Its minimal invasiveness has significantly increased treatment rates, but economic evaluations omit this benefit, risking undervaluation. We evaluated TAVR in elderly US severe symptomatic AS patients, using payer perspective cost-utility analysis (CUA) and societal perspective cost-benefit analysis (CBA). Both CUA and CBA incorporated TAVR's impact on treatment rates. Given patient preferences for treatment options promoting active aging, our CBA used the value of active time as a benefit measure. We found that CUA/CBA net monetary benefits are $212,199/$50,530 per patient. Across risk-, age-, and treatment-eligibility groups, TAVR is the economically optimal treatment choice over surgery and medical management. It represents strong value-for-money per patient and population-wide. Increased treatment uptake accounts for the vast share of TAVR's value.

Respirometric assessment of bacterial kinetics in algae-bacteria and activated sludge processes.

Algae-bacteria (AB) consortia can be exploited for effective wastewater treatment, based on photosynthetic oxygenation to reduce energy requirements for aeration. While algal kinetics have been extensively evaluated, bacterial kinetics in AB systems are still based on parameters taken from the activated sludge models, lacking an experimental validation for AB consortia. A respirometric procedure was therefore proposed, to estimate bacterial kinetics in both activated sludge and AB, under different conditions of temperature, pH, dissolved oxygen, and substrate availability. Bacterial activities were differently influenced by operational/environmental conditions, suggesting that the adoption of typical activated sludge parameters could be inadequate for AB modelling. Indeed, respirometric results show that bacteria in AB consortia were adapted to a wider range of conditions, compared to activated sludge, confirming that a dedicated calibration of bacterial kinetics is essential for effectively modelling AB systems, and respirometry was proven to be a powerful and reliable tool to this purpose.

Productivity analysis in tubular photobioreactors using a dynamic photosynthesis model coupled to computational fluid dynamics particle tracking.

Tubular photobioreactors (TPBRs) are closed devices used for the mass culture of microalgae. TPBRs are supposed to be well-mixed, but the influence of their specific fluid dynamics in photosynthesis efficiency has never been studied in detail. Here, we use Computational Fluid Dynamics (CFD) coupled to a dynamic photosynthesis model to analyze the efficiency of the photosynthetic response in the loop of TPBRs of different sizes (14, 24, 44, 64, and 84 mm) and circulation velocities (0.4 to 1 m s-1). The results show that only the smallest diameters cause enough radial mixing for a photosynthesis-enhancing light regime (integration factor Γ = 0.199 for D = 14 mm and v = 1 m s-1) while high circulation velocities in larger diameters (up to 1 m s-1) increase operating costs but do not enhance photosynthetic productivity. It is also shown the relevance of the characteristic frequency of the strain (ß), which is crucial for high productivity.

Neonatal Immune Neutropenia due to Isoantibodies against the Granulocyte Receptor FcγRIIIb.

INTRODUCTION: Neonatal neutropenia is often secondary to sepsis, low birth weight, pregnancy-induced maternal hypertension, and other conditions. CASE REPORT: We report a case of asymptomatic isoimmune neutropenia in a pair of preterm twins. Genotyping confirmed that the mother was negative for HNA-1a, 1b, and 1c, consistent with an FcγRIIIb deficiency. The father was 1(a+b+c-) and the neonates were 1(a-b+c-). A strongly positive result was observed in the granulocyte immunofluorescence test against paternal neutrophils (IgG antibodies). IgG anti-CD16b isoantibodies were detected in the mother's breast milk. Neutropenia resolved after 28 days without requiring any specific treatments. DISCUSSION: Even though neonatal alloimmune neutropenia (NAN) is usually benign and self-limiting, some patients pre-sent with delayed separation of the umbilical cord, mild skin infections, omphalitis, or severe infections like pneumonia, sepsis, and meningitis. Thus, it is important to rule out NAN in case of neonatal neutropenia.

Modelling of photosynthesis, respiration, and nutrient yield coefficients in Scenedemus almeriensis culture as a function of nitrogen and phosphorus.

Photo-respirometric tecniques are applied for evaluating photosynthetic activity in phototrophic organisms. These methods allow to evaluate photosynthetic response under different conditions. In this work, the influence of nutrient availability (nitrate, ammonium, and phosphate) on the photosynthesis and respiration of Scenedesmus almeriensis was studied using short photo-respirometric measurements. Both photosynthesis and respiration increasing until saturation value and consecutively diminishing, presenting inhibition by high concentrations. Regarding the influence of phosphorus concentration in microalgae cells, a similar hyperbolic trend was observed but no inhibition was observed at high concentration. Based on these experimental data, the respiration, and the photosynthesis rate of S. almeriensis were modelled using Haldane equation for nitrate and ammonium data, and Monod equation for phosphate data. In addition, experiments were performed to determine the yield coefficients for both nitrogen and phosphorus in S. almeriensis cultures. The data showed that the nitrogen and phosphorous coefficient yields are not constant, being modified as a function of nutrients concentration, presenting the luxury uptake phenomena. Finally, the proposed models were incorporated into a simulation tool to evaluate the photosynthetic activity and the nutrient yield coefficients of S. almeriensis when different culture media and wastewaters are used as a nitrogen and phosphorous source for its growth. Key points • Microalgal photosynthesis/respiration vary as a function of nutrients availability. • Photosynthesis inhibition appears at high N-NO 3 - and N-NH4+ concentrations. • Nutrient yield coefficients are influenced by luxury uptake phenomenon.

Analysis of productivity in raceway photobioreactor using computational fluid dynamics particle tracking coupled to a dynamic photosynthesis model.

Raceway photobioreactors (RWPs) are the most common and affordable device for the mass culture of microalgae but due to geometry and the requirement of low input power, its photosynthetic performance is low. The fluid dynamics of RWPs have been studied for information such as energy dissipation and shear rate, CFD has never been used to analyze photosynthesis efficiency by coupling dynamic photosynthesis models with microalgae trajectories. In this work, we investigate by CFD simulation the effect of circulation velocities between 0.2 and 0.8 m s-1in a 0.15 m-1 deep RWPs under standard outdoor conditions to shows that in all circumstances the RWP from the point o view of photosynthesis operates as a perfectly segregated device (no mixing) and that the average growth rate is the result of the integration of the local growth rates at different depths (integration factor Γ = 0).

Massive intrasplenic arterial thrombosis in a patient with chronic ITP during the development of an Evans syndrome.

Long-term safety and efficacy of eltrombopag in adults with persitent/chronic primary immune thrombocytopenia (ITP) evaluated in EXTEND study, showed a high response rate (80%) but, in the clinical safety study, it was observed that 6% of the patients presented venous and arterial thrombotic events. In addition, in the course of the disease, autoimmune hemolytic anemia (Evans syndrome, ES) may occur and could increase the risk of thrombosis. We report an interesting case of splenic rupture due to massive intrasplenic arterial thrombosis in the course of ES in a patient with chronic ITP treated with eltrombopag. The purpose of this case report is to highlight the potential increase in thrombotic risk that may involve the use of eltrombopag in hemolysis situations in patients with ITP.

Variables related to chronic immune thrombocytopenia: experience from a single center and comparison to a meta-analysis.

Classically, several variables have been related to the disease course of chronic primary immune thrombocytopenia (cITP), though to date, there is no consensus on their clinical relevance. In a recent systematic review, a meta-analysis was made and confirmed the existence of certain cITP-related variables that may be related to prognosis in pediatric patients. We retrospectively analyzed a cohort of patients diagnosed with ITP, identified prognostic variables, and compared our results to the variables described by the authors. A multivariate study revealed that older age at diagnosis and higher platelet count were the only independent variables related to cITP. Children up to age 4 years and those with lower platelet counts (below 20 × 109/L) were at lower risk for cITP.Conclusion: We therefore concluded that only age and platelet count at diagnosis are independent variables that should be considered when evaluating the risk of developing cITP. What is Known: • Around 20% of patients with immune thrombocytopenia progress to chronic disease as determined by a sustained platelet count below 100×109/L for more than 12 months. • A number of variables potentially related to the development of cITP are being studied, such as age, sex, cell count, and previous treatment. What is New: • This is a new group of patients diagnosed with ITP in which the platelet count and age at diagnosis are the only independent variables closely related to cITP. • In this new series, we could not confirm other variables previously related to cITP such as total leukocyte count or the absence of treatment at diagnosis.

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

Indirect costs of adult pneumococcal disease and the productivity-based rate of return to the 13-valent pneumococcal conjugate vaccine for adults in Turkey.

Productivity benefits of health technologies are ignored in typical economic evaluations from a health payer's perspective, risking undervaluation. We conduct a productivity-based cost-benefit analysis from a societal perspective and estimate indirect costs of adult pneumococcal disease, vaccination benefits from the adult 13-valent pneumococcal conjugate vaccine (PCV13 Adult), and rates of return to PCV13 Adult for a range of hypothetical vaccination costs. Our context is Turkey's funding PCV13 for the elderly and for non-elderly adults with select comorbidities within the Ministry of Health's National Immunization Program. We use a Markov model with one-year cycles. Indirect costs from death or disability equal the expected present discounted value of lifetime losses in the infected individual's paid and unpaid work and in caregivers' paid work. Vaccination benefits comprise averted indirect costs. Rates of return equal vaccination benefits divided by vaccination costs, minus one. Input parameters are from public data sources. We model comorbidities' effects by scalar multiplication of the parameters of the general population. Indirect costs per treatment episode of inpatient community-acquired pneumonia (CAP), bacteremia, and meningitis - but not for outpatient CAP - approach or exceed Turkish per capita gross domestic product. Vaccination benefits equal $207.02 per vaccination in 2017 US dollars. The rate of return is positive for all hypothetical costs below this. Results are sensitive to herd effects from pediatric vaccination and vaccine efficacy rates. For a wide range of hypothetical vaccination costs, the rate of return compares favorably with those of other global development interventions with well-established strong investment cases.

Evaluation of native microalgae from Tunisia using the pulse-amplitude-modulation measurement of chlorophyll fluorescence and a performance study in semi-continuous mode for biofuel production.

BACKGROUND: Microalgae are attracting much attention as a promising feedstock for renewable energy production, while simultaneously providing environmental benefits. So far, comparison studies for microalgae selection for this purpose were mainly based on data obtained from batch cultures, where the lipid content and the growth rate were the main selection parameters. The present study evaluates the performance of native microalgae strains in semi-continuous mode, considering the suitability of the algal-derived fatty acid composition and the saponifiable lipid productivity as selection criteria for microalgal fuel production. Evaluation of the photosynthetic performance and the robustness of the selected strain under outdoor conditions was conducted to assess its capability to grow and tolerate harsh environmental growth conditions. RESULTS: In this study, five native microalgae strains from Tunisia (one freshwater and four marine strains) were isolated and evaluated as potential raw material to produce biofuel. Firstly, molecular identification of the strains was performed. Then, experiments in semi-continuous mode at different dilution rates were carried out. The local microalgae strains were characterized in terms of biomass and lipid productivity, in addition to protein content, and fatty acid profile, content and productivity. The marine strain Chlorella sp. showed, at 0.20 1/day dilution rate, lipid and biomass productivities of 35.10 mg/L day and 0.2 g/L day, respectively. Moreover, data from chlorophyll fluorescence measurements demonstrated the robustness of this strain as it tolerated extreme outdoor conditions including high (38 °C) and low (10 °C) temperature, and high irradiance (1600 µmol/m2 s). CONCLUSIONS: Selection of native microalgae allows identifying potential strains suitable for use in the production of biofuels. The selected strain Chlorella sp. demonstrated adequate performance to be scaled up to outdoor conditions. Although experiments were performed at laboratory conditions, the methodology used in this paper allows a robust evaluation of microalgae strains for potential market applications.

Evaluation of photosynthetic light integration by microalgae in a pilot-scale raceway reactor.

The improvement of photosynthetic efficiency in a 100 m2 raceway reactor by enhancement of light regime to which the cells are exposed is here reported. From Computational Fluid Dynamics it was calculated that the light exposure times ranged from 0.4 to 3.6 s while the exposure times to darkness were much longer, from 6 to 21 s. It was demonstrated that these times are too long for light integration, the cells fully adapting to local irradiances. This phenomenon was validated in the real outdoor raceway at different seasons. Simulations allows to confirm that if total light integration is achieved biomass productivity can increase up to 40 g/m2·day compared to 29 g/m2·day obtained considering local adaptation, which is close to the experimental value of 25 g/m2·day. This paper provides clear evidence of microalgae cell adaptation to local irradiance because of the unfavourable cell movement pattern in raceway reactors.