Specific Test Panels for Patients With Heart Failure: Implementation and Use in the Spanish National Health System

[Abstract] Objectives. The use of specific test panels (STP) for heart failure (HF) could help improve the management of this condition. The purpose of this study is to gain an insight into the level of implementation of STPs in the management of HF in Spain and gather the opinions of experts, with a special focus on parameters related to iron metabolism. Methods. The opinions of experts in HF were gathered in three stages STAGE 1 as follows: level of implementation of STPs (n=40). STAGE 2: advantages and disadvantages of STPs (n=12). STAGE 3: level of agreement with the composition of three specific STPs for HF: initial evaluation panel, monitoring panel, and de novo panel (n=16). Results. In total, 62.5% of hospitals used STPs for the clinical management of HF, with no association found between the use of STPs and the level of health care (p=0.132) and location of the center (p=0.486) or the availability of a Heart Failure Unit in the center (p=0.737). According to experts, the use of STPs in clinical practice has more advantages than disadvantages (8 vs. 3), with a notable positive impact on diagnostics. Experts gave three motivations and found three limitations to the implementation of STPs. The composition of the three specific STPs for HF was viewed positively by experts. Conclusions. Although the experts interviewed advocate the use of diagnostic and monitoring STPs for HF, efforts are still necessary to achieve the standardization and homogenization of test panels for HF in Spanish hospitals

Metabolic syndrome and Growth Differentiation Factor 15 in older adults

This is a pre-print of an article published in GeroScience. The final authenticated version is available online at: https://doi.org/10.1007/s11357-021-00370-wGrowth Differentiation Factor 15 (GDF-15) is a cytokine produced in response to tissue injury and inflammatory states that may capture distinct pathways between the risk factors aggregated within metabolic syndrome (MS) and the development of diabetes and cardiovascular disease. Objective: To study the association of MS and its components with GDF-15 among older adults, examining the roles of body fat distribution, glucose metabolism, and inflammation. Methods: Data were taken from the Seniors-ENRICA-2 study in Spain, which included 1938 non-institutionalized individuals aged ≥65 years free of diabetes and cardiovascular disease. MS was defined as the presence of ≥3 of the following components: high waist circumference, elevated fasting blood glucose levels, raised blood pressure, increased triglyceride levels; and low serum high-density lipoprotein (HDL) cholesterol. Statistical analyses were performed with linear regression models and adjusted for potential sociodemographic and lifestyle confounders. Results: MS was associated with higher GDF-15 levels (fully adjusted mean increase [95% confidence interval] = 9.34% [5.16,13.7]). The MS components showing the strongest associations were high waist circumference (6.74% [2.97,10.6]), elevated glucose levels (4.91% [0.77,9.23]), and low HDL-cholesterol (8.13% [3.51,13.0]). High waist-to-hip ratio (7.07% [2.63,11.7]), urine albumin (12.1% [2.57,22.5]), and C-reactive protein (10.4% [3.89,17.3]) were also associated with increased GDF-15. Conclusion: MS was associated with higher GDF-15 levels in older adults. Abdominal obesity, hyperglycemia -possibly linked to microvascular disease, as inferred from elevated urine albumin-, low HDL-cholesterol, and inflammation were the main drivers of this associationThis work was supported by the Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE (FIS grants 18/287, 19/319); grant 2020/017 from the National Plan on Drug Addiction (Ministry of Health), and the MITOFUN project grant from the Fundación Francisco Soria Melguiz

Device-measured movement behaviors and cardiac biomarkers in older adults without major cardiovascular disease: the Seniors-ENRICA-2 study

Background: High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are biomarkers of myocardial infarction and heart failure, respectively, and indicate cardiovascular risk. Since low physical activity (PA) and sedentary behavior (SB) are also associated with higher cardiovascular risk, and this association could be a consequence of higher levels of cardiac biomarkers, we examined the association of device-measured movement behaviors with hs-cTnT and NT-proBNP in older men and women without major cardiovascular disease (CVD). Methods: We used data from 1939 older adults from the Seniors-ENRICA-2 study. Accelerometers were used to assess time spent in sleep, SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). Linear regression models were fitted separately in eight strata defined by sex, by median total PA time, and by the presence of subclinical cardiac damage according to cardiac biomarkers levels. Results: In the less active men with subclinical cardiac damage, spending 30 min/day more of MVPA was associated with a mean percentage difference (MPD) (95% confidence interval) in hs-cTnT of - 13.1 (- 18.3, - 7.5); MPDs in NT-proBNP per 30 min/day increment were 5.8 (2.7, 8.9) for SB, - 19.3 (- 25.4, - 12.7) for LPA and - 23.1 (- 30.7, - 14.6) for MVPA. In women with subclinical cardiac damage who were less physically active, 30 min/day more of SB, LPA and MVPA were associated with MPDs in hs-cTnT of 2.1 (0.7, 3.6), - 5.1 (- 8.3, - 1.7) and - 17.5 (- 22.9, - 11.7), respectively, whereas in those more active, LPA and MVPA were associated with MPDs of 4.1 (1.2, 7.2) and - 5.4 (- 8.7, - 2.0), respectively. No associations were found with NT-proBNP in women. Conclusions: The relationship between movement behaviors and cardiac biomarkers in older adults without major CVD depends on sex, subclinical cardiac damage and PA level. More PA and less SB were generally related to lower cardiac biomarkers levels among less active individuals with subclinical cardiac damage, with greater benefits for hs-cTnT in women than men and no benefits for NT-proBNP in women.This work was supported by Instituto de Salud Carlos III, State Secretary of R+D+I and Fondo Europeo de Desarrollo Regional / Fondo Social Europeo (Fondo de Investigaciones Sanitarias grants 18/287, 19/319). DMG is supported by a Ramón y Cajal contract from the Ministry of Science, Innovation and Universities and Fondo Europeo de Desarrollo Regional / Fondo Social Europeo (RYC-2016-20546) and VCS by a Juan de la Cierva contract from the Ministry of Science, Innovation and Universities (IJC2018–038008-I). Reagents for measuring hs-cTnT and NT-proBNP have been provided by Roche Diagnostics International through a Research Agreement with the FUAM (Fundación de la Universidad Autónoma de Madrid). The funding agencies had no role in study design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit this manuscript for publication.S

Association between a Mediterranean lifestyle and growth differentiation factor 15: The seniors ENRICA-2 cohort

Background: Growth Differentiation Factor 15 (GDF-15) is a marker of inflammation and oxidative stress that has been associated with multiple age-related chronic diseases. Since lifestyle is key for preventing these adverse health outcomes, we examined the association between a Mediterranean lifestyle and GDF-15 serum concentrations in Spanish older adults. Methods: We used cross-sectional data from 2502 older adults participating in the Seniors ENRICA-2 cohort. Adherence to the Mediterranean lifestyle was assessed with the 27-item MEDLIFE index, divided into three blocks: 1) "Mediterranean food consumption, 2) Mediterranean dietary habits, 3) Physical activity, rest, social habits, and conviviality". Analyses of the association between the MEFLIFE index and GDF-15 concentrations were performed using multivariable linear regression models adjusting for the main potential confounders. Results: The MEDLIFE index was inversely associated with GDF-15. Compared with participants in the lowest quartile of the MEDLIFE score, GDF-15 mean percentage differences (95% CI) were -3.0% (-8.0, 2.3) for the second quartile, -8.7% (-13.0, -4.1) for the third quartile, and -10.1% (-15.0, -4.9) for the fourth quartile (p-trend<0.001). Block 3 of MEDLIFE, and particularly doing sufficient physical activity, adequate sleep duration, and participating in collective sports, was individually linked to lower concentrations of GDF-15. Results remained similar after excluding participants with cardiovascular disease, type 2 diabetes, or obesity. Conclusions: A Mediterranean lifestyle was associated with reduced levels of GDF-15, suggesting that a combination of multiple lifestyles may be an integral approach to reduce chronic inflammation and disease burden in older adults.This work was supported by the Institute of Health Carlos III; the Secretary of R+D+I; the European Regional Development Fund/European Social Fund (FIS grants 19/319, 20/00896); the National Plan on Drugs (grant 2020/17); Fundación Soria Melguizo (MITOFUN project); Ministry of Science, Innovation and Universities (RYC 2018-02069I to MSP); Universidad Autonóma de Madrid (FPI contract to JMR); FACINGLCOVID-CM project, Funding REACT EU Program (Comunidad de Madrid, European Regional Development Fund). Reagents for measuring Growth Differentiation Factor 15 have been provided by Roche Diagnostics International through a Research Agreement with the FUAM (Fundación de la Universidad Autonóma de Madrid). The funding agencies had no role in study design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit this manuscript for publication.S

Association between a Mediterranean lifestyle and growth differentiation factor 15: The seniors ENRICA-2 cohort

Background: Growth Differentiation Factor 15 (GDF-15) is a marker of inflammation and oxidative stress that has been associated with multiple age-related chronic diseases. Since lifestyle is key for preventing these adverse health outcomes, we examined the association between a Mediterranean lifestyle and GDF-15 serum concentrations in Spanish older adults. Methods: We used cross-sectional data from 2502 older adults participating in the Seniors ENRICA-2 cohort. Adherence to the Mediterranean lifestyle was assessed with the 27-item MEDLIFE index, divided into three blocks: 1) “Mediterranean food consumption, 2) Mediterranean dietary habits, 3) Physical activity, rest, social habits, and conviviality”. Analyses of the association between the MEFLIFE index and GDF-15 concentrations were performed using multivariable linear regression models adjusting for the main potential confounders. Results: The MEDLIFE index was inversely associated with GDF-15. Compared with participants in the lowest quartile of the MEDLIFE score, GDF-15 mean percentage differences (95% CI) were − 3.0% (− 8.0, 2.3) for the second quartile, − 8.7% (− 13.0, − 4.1) for the third quartile, and − 10.1% (− 15.0, − 4.9) for the fourth quartile (ptrend<0.001). Block 3 of MEDLIFE, and particularly doing sufficient physical activity, adequate sleep duration, and participating in collective sports, was individually linked to lower concentrations of GDF-15. Results remained similar after excluding participants with cardiovascular disease, type 2 diabetes, or obesity. Conclusions: A Mediterranean lifestyle was associated with reduced levels of GDF-15, suggesting that a combination of multiple lifestyles may be an integral approach to reduce chronic inflammation and disease burden in older adultsThis work was supported by the Institute of Health Carlos III; the Secretary of R+D+I; the European Regional Development Fund/European Social Fund (FIS grants 19/319, 20/00896); the National Plan on Drugs (grant 2020/17); Fundacion ´ Soria Melguizo (MITOFUN project); Ministry of Science, Innovation and Universities (RYC 2018-02069I to MSP); Universidad Autonoma ´ de Madrid (FPI contract to JMR); FACINGLCOVID-CM project, Funding REACT EU Program (Comunidad de Madrid, European Regional Development Fund). Reagents for measuring Growth Differentiation Factor 15 have been provided by Roche Diagnostics International through a Research Agreement with the FUAM (Fundacion ´ de la Universidad Autonoma ´ de Madrid). The funding agencies had no role in study design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit this manuscript for publicatio

Efectos de la pandemia COVID-19 en la actividad asistencial de los laboratorios clínicos españoles, evolución 2019–2021

Objetivos. Cuantificar el impacto de la pandemia en la actividad asistencial de los laboratorios clínicos españoles. Métodos. Estudio descriptivo, observacional, retrospectivo y multicéntrico. Resultados. De marzo a diciembre de 2020 hubo un descenso estadísticamente significativo en el número de solicitudes (−17.7%, p=&lt;0,001) y análisis totales (−18,3%, p&lt;0,001) respecto al mismo periodo de 2019. Se redujo el número de solicitudes de Atención Primaria en un 37,4% (p&lt;0,001) y el número de mediciones de sangre oculta en heces (−45,8%), análisis cualitativo de orina (−30,1%), antígeno prostático específico (PSA) (−28,5%), tirotropina (TSH) (−27,8%), colesterol total (−27,2%) y hemoglobina glicosilada (HbA1c) (−24,7%), p&lt;0,001. Se observó un aumento significativo del número de solicitudes de UCI (76,6%, p&lt;0,001) y del número de mediciones de IL-6 (+22,350,9), dímero-D (+617,2%), troponina (+46,8%) y gasometría arterial (+35,9%), p&lt;0,001. Durante los seis primeros meses de 2021, existieron diferencias significativas para análisis cualitativo de orina (−8,7%, p&lt;0,001), PSA (−6,3%, p=0,009), IL-6 (+66.269,2, p&lt;0,001), dímero-D (+603,6%, p&lt;0,001), troponina (+28,7%, p&lt;0,001), gasometría arterial (+26,2%, p=0,014) y ferritina (+16,0%, p=0,002). Conclusiones. Los laboratorios clínicos españoles han sufrido un cambio en el origen de sus solicitudes y en la demanda de pruebas. Se han incrementado aquellas utilizadas en la evaluación y seguimiento de los pacientes COVID-19, y han disminuido las dirigidas al control de los pacientes no-COVID y a cribados poblacionales. El análisis a más largo plazo refleja una recuperación en las pruebas dirigidas al control de las enfermedades crónicas y se mantiene el aumento del número de mediciones de los biomarcadores utilizados en el manejo de los pacientes COVID-19

Effects of the COVID-19 pandemic on the activity of clinical laboratories in Spain, evolution in the 2019–2021 period

Objectives. To assess the impact of the COVID-19 pandemic on the activity of clinical laboratories in Spain. Methods. A descriptive, observational, retrospective, multicenter study. Results. Between March and December 2020, there was a statistically significant decrease in the number of test requests (−17.7%, p=&lt;0.001) and total tests performed (−18.3%, p&lt;0.001) with respect to the same period in 2019. A decrease was observed in the number of requests from primary care (−37.4%) (p&lt;0.001) and in the number of foecal occult blood (−45.8%); qualitative urine (−30.1%); PSA (−28.5%); TSH (−27.8%); total cholesterol (−27.2%) and HbA1c (−24.7%) tests performed, p&lt;0.001. A significant increase was found in the number of requests from ICUs (76.6%, p&lt;0.001) and number of IL-6 (+22,350.9), D-dimer (+617.2%), troponin (+46.8%) and arterial blood gas (+3.9%) tests carried out, p&lt;0.001. During the first months of 2021, there were significant changes in the number of requests for qualitative urine (−8.7%, p&lt;0.001), PSA (−6.3%, p=0.009), IL-6 (+66,269.2, p&lt;0.001), D-dimer (+603.6%, p&lt;0.001), troponin (+28.7%, p&lt;0.001), arterial blood gas (+26,2%, p=0.014) and ferritin (+16.0%, p=0.002) tests performed. Conclusions. There were changes in the origin and number of test requested to clinical laboratories in Spain. The number of requests for the evaluation and monitoring of COVID-19 patients increased, whereas requests for the control of non-COVID patients and for population screening decreased. Long-term analysis reveals that the volume of tests performed for the control of chronic diseases returned to normal over time, whereas the increase observed in the volume of tests performed for the management of COVID-19 patients is maintained

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser

The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer’s cut-offs. Sample turnaround time (TAT) was examined. Imprecision repeatability CVs were 1.1–4.7% and within-lab imprecision were 1.8–7.6% (10.0–25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer’s values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories

Iodotyrosines are biomarkers for preclinical stages of iodine-deficient hypothyroidism in Dehal1 knockout mice

BACKGROUND: Iodine is required for the synthesis of thyroid hormone (TH), but its natural availability is limited. Dehalogenase1 (Dehal1) recycles iodine from mono- and di-iodotyrosines (MIT, DIT) to sustain TH synthesis when iodine supplies are scarce, but its role in the dynamics of storage and conservation of iodine is unknown. METHODS: Dehal1 knockout mice (Dehal1KO) were generated by gene-trapping and the timing of expression and distribution was investigated by X-Gal staining and immunofluorescence using recombinant Dehal1-Betagalactosidase protein produced in fetuses and adult mice. Adult Dehal1KO and wild-type (Wt) animals were fed normal and iodine-deficient diets for 1 month and plasma, urine, and tissues were isolated for analyses. TH status was monitored including T4, T3, MIT, DIT, and urinary iodine concentration using a novel LC-MS-MS method and the Sandell-Kolthoff (S-K) technique throughout the experimental period. RESULTS: Dehal1 is highly expressed in the thyroid, is also present in kidneys, liver, and, unexpectedly, the choroid plexus. In vivo transcription of Dehal1 was induced by iodine deficiency only in the thyroid tissue. Under normal iodine intake, Dehal1KO mice were euthyroid but they showed negative iodine balance due to a continuous loss of iodotyrosines in the urine. Counter-intuitively, the urinary iodine concentration of Dehal1KO mice is two-fold higher than in Wt mice, indicating S-K measures both inorganic and organic iodine. Under iodine restriction, Dehal1KO mice rapidly develop profound hypothyroidism while Wt mice remain euthyroid, suggesting reduced retention of iodine in Dehal1KO mice. Urinary and plasma iodotyrosines were continually elevated throughout their life cycle, including the neonatal period, when pups are still euthyroid. CONCLUSIONS: Plasma and urine iodotyrosine elevation occurs in Dehal1-deficient mice throughout life. Therefore, measurement of iodotyrosines predicts an eventual iodine shortage and development of hypothyroidism in the pre-clinical phase. The prompt establishment of hypothyroidism upon the start of iodine restriction suggests that Dehal1KO mice have low iodine reserves in their thyroid glands, pointing to defective capacity for iodine storage

Eficacia de una vía de alta resolución en la evaluación del cólico renoureteral no complicado en un servicio de urgencias hospitalario: un ensayo clínico aleatorizado (Estudio STONE).

Objetivo. Evaluar una vía de alta resolución (vía POC) que utiliza análisis en el punto de atención (point-of-care testing –POCT–) y ecografía en el punto de atención (point-of-care ultrasonography –POCUS–) en la sospecha del cólico renoureteral (CRU) no complicado y compararla con la vía estándar (vía STD). Método. Ensayo clínico aleatorizado, controlado, no ciego, realizado en un servicio de urgencias hospitalario (SUH). Incluyó pacientes con sospecha clínica de CRU agudo y se aleatorizaron 1:1 a seguir vía POC o vía STD. Se analizó el tiempo de estancia en el SUH, el tratamiento administrado, la proporción de diagnósticos alternativos a CRU y las complicaciones a 30 días. Resultados. Entre noviembre de 2018 y octubre de 2019, se reclutaron 140 pacientes de los que se analizaron 124. El tiempo de estancia total en el SUH de la vía POC fue de 112 minutos (DE 45) y en la vía STD 244 minutos (DE 102) (p < 0,001). No hubo diferencias en el tratamiento administrado en urgencias, en el número de diagnósticos alternativos, ni en las complicaciones a 30 días. Conclusiones. La utilización de una vía de alta resolución del manejo del CRU en un SUH es eficaz, segura y reduce el tiempo de estancia en urgencias.post-print225 K