Biological variation of inflammatory and iron metabolism markers in high-endurance recreational athletes; are these markers useful for athlete monitoring?

OBJECTIVES: To deliver biological variation (BV) data for serum hepcidin, soluble transferrin receptor (sTfR), erythropoietin (EPO) and interleukin 6 (IL-6) in a population of well-characterized high-endurance athletes, and to evaluate the potential influence of exercise and health-related factors on the BV. METHODS: Thirty triathletes (15 females) were sampled monthly (11 months). All samples were analyzed in duplicate and BV estimates were delivered by Bayesian and ANOVA methods. A linear mixed model was applied to study the effect of factors related to exercise, health, and sampling intervals on the BV estimates. RESULTS: Within-subject BV estimates (CVI) were for hepcidin 51.9 % (95 % credibility interval 46.9-58.1), sTfR 10.3 % (8.8-12) and EPO 27.3 % (24.8-30.3). The mean concentrations were significantly different between sex, but CVI estimates were similar and not influenced by exercise, health-related factors, or sampling intervals. The data were homogeneously distributed for EPO but not for hepcidin or sTfR. IL-6 results were mostly below the limit of detection. Factors related to exercise, health, and sampling intervals did not influence the BV estimates. CONCLUSIONS: This study provides, for the first time, BV data for EPO, derived from a cohort of well-characterized endurance athletes and indicates that EPO is a good candidate for athlete follow-up. The application of the Bayesian method to deliver BV data illustrates that for hepcidin and sTfR, BV data are heterogeneously distributed and using a mean BV estimate may not be appropriate when using BV data for laboratory and clinical applications.

Krebs von den Lungen-6 (KL-6) Levels in Post-COVID Follow-Up: Differences According to the Severity of COVID-19.

To evaluate KL-6 levels in medium-term post-COVID and to compare them in three groups categorised by the severity of COVID-19, we conducted a real-world, retrospective, cohort study. Data from the COVID-19 episode and follow-up during the post-COVID phase were extracted from the COVID@HULP and POSTCOVID@HULP databases, respectively. For the post-COVID period we included demographics, medical history, symptoms, quality of life, physical activity, anxiety and depression status and laboratory results. Patients were categorised into three groups based on the severity of COVID-19: Group 1 (inpatient critical), Group 2 (inpatient non-critical) and Group 3 (hospitalised at home). KL-6 was measured during the follow-up of the three groups. In all, 802 patients were included (Group 1 = 59; Group 2 = 296; Group 3 = 447 patients). The median age was 59 years (48-70), and 362 (45.2%) were males. At admission, fibrinogen and ferritin levels were lower in Group 3 than in the other groups (p < 0.001). Follow-up data were obtained 124 days (97-149) after the diagnosis of COVID-19. The median levels of fibrinogen, ferritin and KL-6 at follow-up were 336 mg/dL (276-413), 80.5 ng/mL (36-174.3) and 326 U/mL (240.3-440.3), respectively. KL-6 levels were lower in Group 3 than in the other groups (298 U/mL (231.5-398) vs. 381.5 U/mL (304-511.8) (Group 1) and 372 U/mL (249-483) (Group 2) (p < 0.001)). KL-6 was associated with ferritin (p < 0.001), fibrinogen (p < 0.001), D-dimer (p < 0.001) and gamma-glutamyl transferase (p < 0.001). KL-6 levels are less elevated at medium-term post-COVID follow-up in patients with mild COVID-19 than in those with moderate or severe disease. KL-6 is associated with systemic inflammatory, hepatic enzyme and thrombosis biomarkers.

Impact of COVID-19 pandemic on HbA1c management and results in pediatric and adult outpatients with diabetes.

Objectives: Diabetes mellitus intensify the risks and complications related to COVID-19 infection. A major effect of the pandemic has been a drastic reduction of in-person visits. The aim of this study was to evaluate the impact of the COVID-19 pandemic on HbA1c management and results among pediatric and adult outpatients with diabetes, considering the laboratory and point-of-care testing (POCT) HbA1c measurements. Methods: Observational retrospective study including patients from pediatric and adult diabetes units was conducted. HbA1c results obtained in the laboratory and POCT over 3 years (2019-2021) were collected from the laboratory information system. Results: After the lockdown, the number of HbA1c plummeted. Children returned soon to routine clinical practice. The number of HbA1c increased gradually in adults, especially in POCT. Globally, HbA1c results were lower in children compared with adults (p<0.001). HbA1c values in children (p<0.001) and adults (p=0.002) decreased between pre-pandemic and post-pandemic periods, though lower than the HbA1c reference change value. The percentage of HbA1c results above 8% remained stable during the study period. Conclusions: Continuous glucose monitoring and a telemedicine have been crucial, even allowing for improvements in HbA1c results. During the lockdown, patients with better metabolic control were managed in the laboratory whereas patients with poorer control or a severe clinical situation were attended in diabetes units by POCT. Adults returned to pre-pandemic management slowly because they were more susceptible to morbidity and mortality due to COVID-19. Coordination among all health professionals has been essential to offering the best management, especially in difficult scenarios such as the COVID-19 pandemic.

State of affairs and future challenges in laboratory medicine in Spain: an analysis of the Spanish Society of Laboratory Medicine (SEQCML).

Objectives: Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals. Methods: The Spanish Society of Laboratory Medicine distributed a questionnaire among the 250 most representative centers (the ones with the largest volume of determinations and training programs), of which 174 (69.6%) returned the questionnaire providing data for 2019. Results: Laboratories were classified according to the number of determinations. In total, 37% identified themselves as small (<1 million determinations per year); 40% considered themselves medium-sized (1-5 million determinations per year) and 23% considered they were large laboratories (>5 million determinations). The level of specialization of laboratory physicians and laboratory performance were higher in large laboratories. Most requests (87%) and determinations (93%) corresponded to biochemistry and hematology. As many as 63% of physicians had an indefinite contract, and 23% were older than 60 years. Conclusions: Laboratory medicine is a consolidated discipline that is gaining relevance in Spain. It adds value to the diagnosis, prognosis and follow-up of diseases, and to treatment response monitoring. The results of this study will help us address challenges such as the need for specialized training for laboratory professionals; the emergence of technological innovations; exploitation of Big Data; optimization of quality management systems and patient safety.

Impact of systemic corticosteroids on length of hospitalization among patients with COVID-19. / [Artículo traducido] Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19.

OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. MéTHOD: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median=3 [interquartile range=0-10] vs. 5 [2-8.5]; p=0.005, respectively), showing a 43% greater probability of being hospitalised ≤4 days than >4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤4 days vs. 23.7% hospitalised >4 days [p<0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Impact of systemic corticosteroids on hospital length of stay among patients with COVID-19.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. METHODS: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0-10] vs. 5 [2-8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients.

Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.

Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.

POCT errors can lead to false potassium results.

Point-of-care-testing (POCT) facilitates rapid availability of results that allows prompt clinical decision making. These results must be reliable and the whole process must not compromise its quality. Blood gas analyzers are one of the most used methods for POCT tests in Emergency Departments (ED) and in critical patients. Whole blood is the preferred sample, and we must be aware that hemolysis can occur. These devices cannot detect the presence of hemolysis in the sample, and because of the characteristics of the sample, we cannot visually detect it either. Hemolysis can alter the result of different parameters, including potassium with abnormal high results or masking low levels (hypokalemia) when reporting normal concentrations. Severe hyperkalemia is associated with the risk of potentially fatal cardiac arrhythmia and demands emergency clinical intervention. Hemolysis can be considered the most frequent cause of pseudohyperkalemia (spurious hyperkalemia) or pseudonormokalemia and can be accompanied by a wrong diagnosis and an ensuing inappropriate clinical decision making. A complete review of the potential causes of falsely elevated potassium concentrations in blood is presented in this article. POCT programs properly led and organized by the clinical laboratory can help to prevent errors and their impact on patient care.

Cadmium exposure and growth differentiation factor-15 (GDF-15) levels in non-smoking older adults.

BACKGROUND: Cadmium (Cd) exposure is a risk factor for cardiovascular disease (CVD); however, understanding the effects of Cd at the cellular level remains incomplete. Since growth differentiation factor-15 (GDF-15) is a cytokine produced in many cell types in response to tissue injury and inflammation that may capture several pathways between Cd and CVD, this study examined the relationship between blood Cd levels and serum GDF-15 concentrations in community-dwelling older adults. METHODS: Cd and GDF-15 were measured in 1942 non-smoking individuals aged 65+ with no previous history of CVD. The association of Cd with GDF-15 was evaluated in linear regression models that adjusted for sociodemographic, lifestyle and biological risk factors, inflammatory biomarkers (IL-6, C-reactive protein and neutrophil to lymphocyte ratio), and markers of vascular damage (NTproBNP and cTnT-hs). RESULTS: Geometric mean Cd exposure was 0.11 µg/L (0.09 in never- and 0.15 in former-smokers) and geometric mean GDF-15 was 1186.21 pg/mL (1182.67 in never- and 1191.66 in former-smokers). In multivariable analyses, we found a dose-response association between Cd levels and GDF-15: adjusted mean percentage differences in GDF-15 (95% confidence interval) per 2-fold increase in Cd concentrations in the overall non-smoking population and in never smokers were, respectively, 2.54% (1.01, 4.06) and 2.50% (0.47, 4.54). In spline regression, the dose-response relationship was progressive over the range of Cd concentrations with no significant departures from linearity. CONCLUSIONS: Cd exposure may be related to enhanced GDF-15 expression. Future studies with repeated GDF-15 measurements should confirm the present findings to better understand the biological mechanisms underlying this association.

Plasma Amino Acids and Risk of Impaired Lower-Extremity Function and Role of Dietary Intake: A Nested Case-Control Study in Older Adults.

INTRODUCTION: Amino acids are key elements in the regulation of the aging process which entails a progressive loss of muscle mass. The health effects of plasma amino acids can be influenced by dietary intake. This study assessed the prospective association between amino acid species and impaired lower-extremity function (ILEF) in older adults, exploring the role of diet on this association. METHODS: This is a case-control design comprising 43 incident cases of ILEF and 85 age- and sex-matched controls. Plasma concentrations of 20 amino acid species were measured at baseline using liquid chromatography-tandem mass spectrometry, and incident cases of ILEF were measured after 2 years by means of the Short Physical Performance Battery. Conditional logistic regression models were used to assess longitudinal relationships. RESULTS: After adjusting for potential confounders, higher levels of tryptophan were associated with a decreased 2-year risk of ILEF (OR per 1-SD increase = 0.64, 95% CI = [0.42, 0.97]), while glutamine and total essential amino acids were linked to higher ILEF risk (OR = 1.57, 95% CI = [1.01, 2.45]; OR = 1.89, 95% CI = [1.18, 3.03], respectively). Those with a lower adherence to a Mediterranean diet, a higher BMI, a higher consumption of red meat, and a lower consumption of nuts and legumes had an increased risk of ILEF associated with higher levels of essential amino acids. DISCUSSION/CONCLUSION: Some amino acid species could serve as risk markers for physical function decline in older adults, and healthy diet might attenuate the excess risk of ILEF linked to essential amino acids.

Long-term within- and between-subject biological variation of 29 routine laboratory measurands in athletes.

OBJECTIVES: Within- and between-subject biological variation (BV) estimates have many applications in laboratory medicine. However, robust high-quality BV estimates are lacking for many populations, such as athletes. This study aimed to deliver BV estimates of 29 routine laboratory measurands derived from a Biological Variation Data Critical Appraisal Checklist compliant design in a population of high-endurance athletes. METHODS: Eleven samples per subject were drawn from 30 triathletes monthly, during a whole sport season. Serum samples were measured in duplicate for proteins, liver enzymes, lipids and kidney-related measurands on an Advia2400 (Siemens Healthineers). After outlier and homogeneity analysis, within-subject (CVI) and between-subject (CVG) biological variation estimates were delivered (CV-ANOVA and log-ANOVA, respectively) and a linear mixed model was applied to analyze the effect of exercise and health related variables. RESULTS: Most CVI estimates were similar or only slightly higher in athletes compared to those reported for the general population, whereas two- to three-fold increases were observed for amylase, ALT, AST and ALP. No effect of exercise and health related variables were observed on the CVI estimates. For seven measurands, data were not homogeneously distributed and BV estimates were therefore not reported. CONCLUSIONS: The observation of higher CVI estimates in athletes than what has been reported for the general population may be related to physiological stress over time caused by the continuous practice of exercise. The BV estimates derived from this study could be applied to athlete populations from disciplines in which they exercise under similar conditions of intensity and duration.

Biological variation of venous acid-base status measurands in athletes.

BACKGROUND: Analysis of acid-base status (ABS) is requested in a wide range of clinical scenarios, including in the assessment of athletes' performance and follow up, but there is a lack of high-quality biological variation (BV) data. The aims of this study were to estimate the BV of ABS related parameters in athletes and to evaluate if variables related to exercise may influence the estimates. MATERIAL AND METHODS: Eleven samples from 30 triathletes were drawn, on a monthly basis. The samples were measured for pH, pCO2, bicarbonate, base excess, TCO2, Ca2+ and lactate. A CV-ANOVA was performed to calculate within-subject (CVI) estimates and a linear mixed model was applied to analyze the effect of the folowing variables on the BV; health status, sampling interval, intensity and duration of the exercise. RESULTS: For all ABS parameters except for lactate, higher CVI estimates were found in athletes than what have been reported for the general population. No significant effect of the exercise and sampling related variables were observed, except for Ca2+. CONCLUSION: This difference founds in ABS parameters between athletes and the general population could be explained by the physiological stress during exercise. Laboratories attending this population could use these BV estimates to establish quality goals.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2 ± 15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

ANTECEDENTES: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada. MÉTODOS: Se estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio. RESULTADOS: Se incluyó a 918 pacientes (edad 63,2 ± 15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas). CONCLUSIÓN: La hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos.

POCT Accreditation ISO 15189 and ISO 22870: Making the Point.

ISO 22870 lists specific requirements for the quality and competence of point-of-care testing (POCT), which are intended for medical laboratories in conjunction with ISO 15189. POCT characteristics include the availability of a large number of devices 24 h/day, a variety of analytical methods, clinical settings inside and outside the hospital, and general non-laboratory staff. ISO 22870 accreditation for adequate POCT management therefore poses a challenge for laboratory medicine, which is charged with leading and coordinating POCT with a multidisciplinary committee. La Paz University Hospital has a complex multitest and multisite network that has been accredited since 2017. In our experience, the particularly crucial areas for POCT accreditation are method performance verification, internal and external quality assurance, staff training and competency, and continuous improvement. ISO 22870 and ISO 15189 accreditation have led us to improve numerous areas regarding the total testing process and, consequently, our patients' results.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

Plasma acylcarnitines and risk of lower-extremity functional impairment in older adults: a nested case-control study.

Elevated concentrations of acylcarnitines have been associated with higher risk of obesity, type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the association between L-carnitine and acylcarnitine profiles, and 2-year risk of incident lower-extremity functional impairment (LEFI). This case-control study is nested in the Seniors-ENRICA cohort of community-dwelling older adults, which included 43 incident cases of LEFI and 86 age- and sex- matched controls. LEFI was assessed with the Short Physical Performance Battery. Plasma L-carnitine and 28 acylcarnitine species were measured. After adjusting for potential confounders, medium-chain acylcarnitines levels were associated with 2-year incidence of LEFI [odds ratio per 1-SD increase: 1.69; 95% confidence interval: 1.08, 2.64; p = 0.02]. Similar results were observed for long-chain acylcarnitines [odds ratio per 1-SD increase: 1.70; 95% confidence interval: 1.03, 2.80; p = 0.04]. Stratified analyses showed a stronger association between medium- and long-chain acylcarnitines and incidence of LEFI among those with body mass index and energy intake below the median value. In conclusion, higher plasma concentrations of medium- and long-chain acylcarnitines were associated with higher risk of LEFI. Given the role of these molecules on mitochondrial transport of fatty acids, our results suggest that bioenergetics dysbalance contributes to LEFI.

Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19.

AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.

Characterization of NT-proBNP in a large cohort of COVID-19 patients.

AIMS: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. METHODS AND RESULTS: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). CONCLUSION: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.

Plasma Ceramides and Risk of Impaired Lower-Extremity Function in Older Adults: A Nested Case-Control Study.

BACKGROUND: Higher levels of ceramides have been linked to several chronic diseases; also there is emerging cross-sectional evidence that ceramides are associated with lower physical functioning. This research assessed for the first time the prospective relationship between ceramide species and impaired lower-extremity function (ILEF) in older adults. METHODS: Case-control study with 43 cases of ILEF and 86 age- and sex-matched controls, which was nested in the Seniors-ENRICA cohort of community-dwelling older adults. Incident ILEF from 2015 to 2017 was ascertained with the Short Physical Performance Battery. In 2015, 27 ceramide species were measured in plasma by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to assess the longitudinal relationship between ceramides concentration and incidence of ILEF. RESULTS: After adjusting for education level, body mass index, alcohol and total energy intake, physical activity, and presence of chronic conditions, some ceramide species were related to 2-year incidence of ILEF. Specifically, the odds ratios of ILEF per 1-SD increase in ceramide concentration were: 1.66 [95% CI = (1.03, 2.68)] for ceramide C14:0, 1.61 (1.00, 2.59) for ceramide C16:0, and 1.64 (1.03, 2.60) for ceramide C16:1 (n-7). In the case of ceramides C16:0 and C16:1 (n-7), a stronger relationship was found in those with a higher body mass index; systolic blood pressure could also mediate the relationship between ceramide C16:1 (n-7) and ILEF (p for interaction = .03). CONCLUSIONS: Higher plasma levels of ceramides C14:0, C16:0, and C16:1 (n-7) are associated with higher risk of ILEF, and might serve as risk markers for functional decline in older adults.