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Exercise can produce transient elevations of cardiac troponin (cTn) concentrations, which may resemble the cTn release profile of myocardial infarction. Consequently, clinical interpretation of postexercise cTn elevations (ie, values above the 99th percentile upper reference limit) remains challenging and may cause clinical confusion. Therefore, insight into the physiological versus pathological nature of postexercise cTn concentrations is warranted. We aim to (1) establish resting and postexercise reference values for recreational athletes engaged in walking, cycling or running exercise; (2) compare the prevalence of (sub)clinical coronary artery disease in athletes with high versus low postexercise cTn concentrations and (3) determine the association between postexercise cTn concentrations and the incidence of major adverse cardiovascular events (MACE) and mortality during long-term follow-up. For this purpose, the prospective TRoponin concentrations following Exercise and the Association with cardiovascular ouTcomes (TREAT) observational cohort study was designed to recruit 1500 recreational athletes aged ≥40 to <70 years who will participate in Dutch walking, cycling and running events. Baseline and postexercise high-sensitivity cTnT and cTnI concentrations will be determined. The prevalence and magnitude of coronary atherosclerosis on computed tomography (eg, coronary artery calcium score, plaque type, stenosis degree and CT-derived fractional flow reserve) will be compared between n=100 athletes with high postexercise cTn concentrations vs n=50 age-matched, sex-matched and sport type-matched athletes with low postexercise cTn concentrations. The incidence of MACE and mortality will be assessed in the entire cohort up to 20 years follow-up. The TREAT study will advance our understanding of the clinical significance of exercise-induced cTn elevations in middle-aged and older recreational athletes. Trial registration number NCT06295081.
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BACKGROUND: Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients. METHODS: The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients. RESULTS: Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40â kDa intact:29â kDa fragment:15 to 18â kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48â h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18â kDa fragments were found for all matrices. CONCLUSIONS: The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18â kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.
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BACKGROUND: Coronary artery calcification (CAC) is associated with poor outcome in critically ill patients. A deterioration in cardiac conduction and loss of myocardial tissue could be an underlying cause. Vectorcardiography (VCG) and cardiac biomarkers provide insight into these underlying causes. The aim of this study was to investigate whether a high degree of CAC is associated with VCG-derived variables and biomarkers, including high-sensitivity troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: Mechanically ventilated coronavirus-19 (COVID-19) patients with an available chest computed tomography (CT) and 12-lead electrocardiogram (ECG) were studied. CAC scores were determined using chest CT scans. Patients were categorized into 3 sex-specific tertiles: low, intermediate, and high CAC. Daily 12 leads-ECGs were converted to VCGs. Daily hs-cTnT and NT-proBNP levels were determined. Linear mixed-effects regression models examined the associations between CAC tertiles and VCG variables, and between CAC tertiles and hs-cTnT or NT-proBNP levels. RESULTS: In this study, 205 patients (73.2% men, median age 65 years [IQR 57.0; 71.0]) were included. Compared to the lowest CAC tertile, the highest CAC tertile had a larger QRS area at baseline (6.65 µVs larger [1.50; 11.81], p = 0.012), which decreased during admission (- 0.27 µVs per day [- 0.43; - 0.11], p = 0.001). Patients with the highest CAC tertile also had a longer QRS duration (12.02 ms longer [4.74; 19.30], p = 0.001), higher levels of log hs-cTnT (0.79 ng/L higher [0.40; 1.19], p < 0.001) and log NT-proBNP (0.83 pmol/L higher [0.30; 1.37], p = 0.002). CONCLUSION: Patients with a high degree of CAC had the largest QRS area and higher QRS amplitude, which decreased more over time when compared to patients with a low degree of CAC. These results suggest that CAC might contribute to loss of myocardial tissue during critical illness. These insights could improve risk stratification and prognostication of patients with critical illness.
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The magnitude of exercise-induced cardiac troponin (cTn) elevations is dependent on cardiovascular health status, and previous studies have shown that occult coronary atherosclerosis is highly prevalent among amateur athletes. We tested the hypothesis that middle-aged and older athletes with coronary atherosclerosis demonstrate greater cTn elevations following a controlled endurance exercise test compared with healthy peers. We included 59 male athletes from the Measuring Athletes' Risk of Cardiovascular events 2 (MARC-2) study and stratified them as controls [coronary artery calcium score (CACS) = 0, n = 20], high CACS [≥300 Agatston units or ≥75th Multi-Ethnic Study of Atherosclerosis (MESA) percentile, n = 20] or significant stenosis (≥50% in any coronary artery, n = 19). Participants performed a cycling test with incremental workload until volitional exhaustion. Serial high-sensitivity cTn (hs-cTn) T and I concentrations were measured (baseline, after 30-min warm-up, and 0, 30, 60, 120, and 180 min postexercise). There were 58 participants (61 [58-69] yr) who completed the exercise test (76 ± 14 min) with a peak heart rate of 97.7 [94.8-101.8]% of their estimated maximum. Exercise duration and workload did not differ across groups. High-sensitivity cardiac troponin T (Hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) concentrations significantly increased (1.55 [1.33-2.14]-fold and 2.76 [1.89-3.86]-fold, respectively) over time, but patterns of cTn changes and the incidence of concentrations >99th percentile did not differ across groups. Serial sampling of hs-cTnT and hs-cTnI concentrations during and following an exhaustive endurance exercise test did not reveal differences in exercise-induced cTn release between athletes with versus without coronary atherosclerosis. These findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.NEW & NOTEWORTHY Exercise-induced cardiac troponin (cTn) release is considered to be dependent on cardiovascular health status. We tested whether athletes with coronary atherosclerosis demonstrate greater exercise-induced cTn release compared with healthy peers. Athletes with coronary atherosclerosis did not differ in cTn release following exercise compared with healthy peers. Our findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.
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Doença da Artéria Coronariana , Pessoa de Meia-Idade , Humanos , Masculino , Idoso , Doença da Artéria Coronariana/diagnóstico , Constrição Patológica , Troponina I , Troponina T , Atletas , BiomarcadoresRESUMO
The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.
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Ponte de Artéria Coronária , Infarto do Miocárdio , Humanos , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/etiologia , Troponina I , Troponina T , BiomarcadoresRESUMO
Myocardial infarction is the most common cause of death worldwide. An understanding of the alterations in protein pathways is needed in order to develop strategies that minimize myocardial damage. To identify the protein signature of cardiac ischemia/reperfusion (I/R) injury in rats, we combined, for the first time, protein matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and label-free proteomics on the same tissue section placed on a conductive slide. Wistar rats were subjected to I/R surgery and sacrificed after 24 h. Protein MALDI-MSI data revealed ischemia specific regions, and distinct profiles for the infarct core and border. Firstly, the infarct core, compared to histologically unaffected tissue, showed a significant downregulation of cardiac biomarkers, while an upregulation was seen for coagulation and immune response proteins. Interestingly, within the infarct tissue, alterations in the cytoskeleton reorganization and inflammation were found. This work demonstrates that a single tissue section can be used for protein-based spatial-omics, combining MALDI-MSI and label-free proteomics. Our workflow offers a new methodology to investigate the mechanisms of cardiac I/R injury at the protein level for new strategies to minimize damage after MI.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Traumatismo por Reperfusão , Animais , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Infarto do Miocárdio/patologia , ReperfusãoRESUMO
Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays. Initial studies suggested the presence of a macromolecule consisting of haptocorrin bound B12. Specific determinations of the B12-binding proteins revealed normal amounts of haptocorrin but a markedly increase in both total and B12 saturated transcobalamin (holo-TC). The results are in accord with the presence of macro-transcobalamin. These experiments reveal that determination of the nature of the B12-macromolecules is troublesome due to differences in assays applied to measure these proteins. In addition, this publication creates awareness of macro-holo-TC as a cause of an unexplained increased B12 level.
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Transcobalaminas , Deficiência de Vitamina B 12 , Humanos , Transcobalaminas/análise , Vitamina B 12RESUMO
Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (ß -0.93 [-1.37; -0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (ß -0.08 [-0.11; -0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.
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COVID-19 , SARS-CoV-2 , Biomarcadores , COVID-19/epidemiologia , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Estudos Prospectivos , Respiração Artificial , Troponina TRESUMO
PURPOSE: Employers play an important role in facilitating sustainable return to work (RTW) by workers with disabilities. The aim of this qualitative study was to explore how employers who were successful in retaining workers with disabilities at work fulfilled their supportive role, and which facilitators were essential to support these workers throughout the RTW process. METHODS: We conducted a semi-structured interview study among 27 employers who had experience in retaining workers with disabilities within their organization. We explored the different phases of RTW, from the onset of sick leave until the period, after 2-years of sick-leave, and when they can apply for disability benefit. We analyzed data by means of thematic analysis. RESULTS: We identified three types of employer support: (1) instrumental (offering work accommodations), (2) emotional (encouragement, empathy, understanding) and (3) informational (providing information, setting boundaries). We identified three facilitators of employer support (at organizational and supervisor levels): (1) good collaboration, including (in)formal contact and (in)formal networks; (2) employer characteristics, including supportive organizational culture and leadership skills; and (3) worker characteristics, including flexibility and self-control. CONCLUSIONS: Employers described three different possible types of support for the worker with disabilities: instrumental, emotional, and informational. The type and intensity of employer support varies during the different phases, which is a finding that should be further investigated. Good collaboration and flexibility of both employer and worker were reported as facilitators of optimal supervisor/worker interaction during the RTW process, which may show that sick-listed workers and their supervisors have a joint responsibility for the RTW process. More insight is needed on how this supervisor/worker interaction develops during the RTW process.
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Pessoas com Deficiência , Retorno ao Trabalho , Emprego , Humanos , Pesquisa Qualitativa , Retorno ao Trabalho/psicologia , Licença MédicaRESUMO
PURPOSE: Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. METHODS: This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. RESULTS: Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6-1.7)) in comparison to placebo treatment (1.5 (1.4-1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). CONCLUSIONS: Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.
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Arterite , Diabetes Mellitus Tipo 2 , Arterite/diagnóstico por imagem , Arterite/tratamento farmacológico , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fluordesoxiglucose F18 , Humanos , Inflamação/tratamento farmacológico , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Resveratrol/uso terapêuticoRESUMO
Various definitions of myocardial infarction type 5 after coronary artery bypass grafting (CABG) have been proposed (myocardial infarction [MI-5], also known as peri-procedural MI), using different biomarkers and different and arbitrary cut-off values. This meta-analysis aims to determine the expected release of high-sensitivity cardiac troponin T (hs-cTnT) after CABG in general and after uncomplicated surgery and off-pump CABG in particular. A systematic search was applied to 3 databases. Studies on CABG as a single intervention and reporting on postoperative hs-cTnT concentrations on at least 2 different time points were included. All data on hs-cTnT concentrations were extracted, and mean concentrations at various points in time were stratified. Eventually, 15 studies were included, encompassing 2,646 patients. Preoperative hs-cTnT was 17 ng/L (95% confidence interval [CI] 13 to 20 ng/L). Hs-cTnT peaked at 6 to 8 hours postoperatively (628 ng/L, 95% CI 400 to 856 ng/L; 45x upper reference limit [URL]) and was still increased after 48 hours. In addition, peak hs-cTnT concentration was 614 ng/L (95% CI 282 to 947 ng/L) in patients with a definite uncomplicated postoperative course (i.e., without MI). For patients after off-pump CABG compared to on-pump CABG, the mean peak hs-cTnT concentration was 186 ng/L (95% CI 172 to 200 ng/L, 13 × URL) versus 629 ng/L (95% CI 529 to 726 ng/L, 45 × URL), respectively. In conclusion, postoperative hs-cTnT concentrations surpass most of the currently defined cut-off values for MI-5, even in perceived uncomplicated surgery, suggesting thorough reassessment. Hs-cTnT release differences following on-pump CABG versus off-pump CABG were observed, implying the need for different cut-off values for different surgical strategies.
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Ponte de Artéria Coronária , Infarto do Miocárdio/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Troponina T/sangue , Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Infarto do Miocárdio/sangue , Período Perioperatório , Complicações Pós-Operatórias/sangueRESUMO
Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.
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Doenças Cardiovasculares/metabolismo , Exercício Físico , Troponina/metabolismo , Humanos , CinéticaRESUMO
Cardiac troponin T (cTnT) is a sensitive and specific biomarker for detecting cardiac muscle injury. Its concentration in blood can be significantly elevated outside the normal reference range under several pathophysiological conditions. The classical analytical method in routine clinical analysis to detect cTnT in serum or plasma is a single commercial immunoassay, which is designed to quantify the intact cTnT molecule. The targeted epitopes are located in the central region of the cTnT molecule. However, in blood cTnT exists in different biomolecular complexes and proteoforms: bound (to cardiac troponin subunits or to immunoglobulins) or unbound (as intact protein or as proteolytic proteoforms). While proteolysis is a principal posttranslational modification (PTM), other confirmed PTMs of the proteoforms include N-terminal initiator methionine removal, N-acetylation, O-phosphorylation, O-(N-acetyl)-glucosaminylation, N(É)-(carboxymethyl)lysine modification and citrullination. The immunoassay probably detects several of those cTnT biomolecular complexes and proteoforms, as long as they have the centrally targeted epitopes in common. While analytical cTnT immunoreactivity has been studied predominantly in blood, it can also be detected in urine, although it is unclear in which proteoform cTnT immunoreactivity is present in urine. This review presents an overview of the current knowledge on the pathophysiological lifecycle of cTnT. It provides insight into the impact of PTMs, not only on the analytical immunoreactivity, but also on the excretion of cTnT in urine as one of the waste routes in that lifecycle. Accordingly, and after isolating the proteoforms from urine of patients suffering from proteinuria and acute myocardial infarction, the structures of some possible cTnT proteoforms are reconstructed using mass spectrometry and presented.
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Infarto do Miocárdio , Troponina T , Humanos , Fosforilação , Processamento de Proteína Pós-Traducional , Proteólise , Troponina T/metabolismoRESUMO
BACKGROUND: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI. METHODS: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added. RESULTS: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively. CONCLUSION: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI. TRIAL REGISTRATION: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.
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Síndrome Coronariana Aguda/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Adenosina/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Vasodilatadores/administração & dosagemRESUMO
Mass spectrometry imaging (MSI) can analyze the spatial distribution of hundreds of different molecules directly from tissue sections usually placed on conductive glass slides to provide conductivity on the sample surface. Additional experiments are often required for molecular identification using consecutive sections on membrane slides compatible with laser capture microdissection (LMD). In this work, we demonstrate for the first time the use of a single conductive slide for both matrix-assisted laser desorption ionization (MALDI)-MSI and direct proteomics. In this workflow, regions of interest can be directly ablated with LMD while preserving protein integrity. These results offer an alternative for MSI-based multimodal spatial-omics.
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Proteômica/instrumentação , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Cromatografia Líquida/métodos , Microdissecção e Captura a Laser , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To gain insight into 1) the symptoms and the disease process of healthcare professionals (HCPs) who tested positive for COVID-19 and were not hospitalized because of mild symptoms, 2) the impact on their psychological well-being and 3) the experiences with (after) care and infection prevention measures. DESIGN: Explorative mixed-methods study. METHOD: The municipal public health services of Groningen and Fryslân invited all HCPs aged above 18 years who tested positive for COVID-19 between March 18th and April 3rd 2020 to fill out an online questionnaire (n = 109), on average one month after diagnosis. 18 HCPs participated in telephone interviews. RESULTS: Almost all HCPs mentioned fatigue as a long-term symptom, less frequently mentioned were, among other things, feeling physically weak and having a cold. Nearly half of them did not have a fever, two-thirds experienced stress. HCPs with comorbidity had more symptoms. The interviews showed that stress in particular occurred in families with children and because of uncertainty about the duration of infectiousness, with lack of good (after)care. Respondents experienced many negative reactions of people in their environment that felt stigmatizing. The isolation at home was considered bearable. CONCLUSION: A COVID-19 infection has a significant impact on physical and mental health, even in HCPs with mild symptoms. Persistent fatigue in particular hinders patients' functioning. The absence of fever in almost half of the respondents is remarkable, as well as the negative impact on psychological well-being. HCPs are also dissatisfied with after-care. Infection prevention measures were relatively well-adhered too.
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Assistência ao Convalescente , COVID-19 , Fadiga , Pessoal de Saúde , Saúde Mental , Estresse Psicológico , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/psicologia , Assistência ao Convalescente/normas , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/psicologia , COVID-19/reabilitação , Autoavaliação Diagnóstica , Fadiga/diagnóstico , Fadiga/etiologia , Feminino , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Avaliação das Necessidades , Países Baixos/epidemiologia , SARS-CoV-2/isolamento & purificação , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologiaRESUMO
According to the European definition, rare diseases are life-threatening or chronically debilitating conditions that affect only 5 out of 10,000 people in the European Union. It is estimated that there are around 6000-8000 different rare diseases, affecting 6-8% of the population in the course of their lives. For the Netherlands, this means that about 1 million people are affected by a rare disease, or one in 17 people. Patients with rare diseases indicate that they often have a long and uncertain diagnostic journey behind them, while the first symptoms present in childhood in 75% of the rare diseases. In this perspective, we discuss some of the results from the research report 'Scherperzicht op diagnostischevertragingbijzeldzameaandoeningen' in which the diagnostic journey for patients with rare diseases is mapped out with figures. We also make recommendations to speed up the diagnostic process for patients with rare diseases.
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Diagnóstico Tardio/tendências , Doenças Raras/diagnóstico , Adulto , Criança , União Europeia , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Doenças Raras/epidemiologiaRESUMO
BackgroundThe course of the disease in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort; MaastrICCht. We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with SARS-CoV-2 infection. Study populationMechanically ventilated patients admitted to the Intensive Care with SARS- CoV-2 infection. Main messageWe will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, electrocardiograms, echocardiography as well as other imaging modalities to assess heterogeneity of the natural course of SARS-CoV-2 infection in critically ill patients. The MaastrICCht cohort is, also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national Intensive Care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. ConclusionThe spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS- CoV-2 infection in mechanically ventilated patients. Our design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht cohort. Strengths and limitations of this studyO_LISerial measurements that characterize the disease course of SARS-CoV-2 infection in mechanically ventilated patients C_LIO_LIData collection and analysis according to a predefined protocol C_LIO_LIFlexible, evolving design enabling the study of multiple aspects of SARS-CoV-2 infection in mechanically ventilated patients C_LIO_LISingle centre, including only ICU patients C_LI