RESUMO
The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.
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Alcanos , COVID-19 , SARS-CoV-2 , Viremia , Viremia/diagnóstico , Viremia/virologia , Humanos , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/virologia , COVID-19/sangue , Alcanos/química , Temperatura , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/análiseAssuntos
Biomarcadores , Troponina I , Troponina T , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores Etários , Biomarcadores/sangue , Troponina I/sangue , Troponina T/sangue , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mmâ Hg or diastolic blood pressure, 80-89 mmâ Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. METHODS: We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. We measured hs-cTnI (high-sensitivity cardiac troponin I), hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. RESULTS: Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. CONCLUSIONS: Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.
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Anti-Hipertensivos , Biomarcadores , Hipertensão , Inquéritos Nutricionais , Fragmentos de Peptídeos , Humanos , Masculino , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Anti-Hipertensivos/uso terapêutico , Adulto , Idoso , Fragmentos de Peptídeos/sangue , Medição de Risco/métodos , Peptídeo Natriurético Encefálico/sangue , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Troponina T/sangue , Troponina I/sangueRESUMO
BACKGROUND: Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)]. METHODS: From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients. Troponin concentrations were randomly varied several times based on absolute deviations of 0.5 to 3â ng/L and relative changes of 2% to 20% around the low-risk threshold (5â ng/L) and URLs, respectively. RESULTS: For both assays at the low-risk thresholds, there were negligible differences in sensitivity (<0.3%) with increasing analytical variation. The proportion of patients characterized as low risk reduced by 30% to 29% (Roche) and 53% to 44% (Abbott). At the URL, increasing analytical variation also did not change sensitivity; the PPV fell by less than 3%. For risk stratification, increased delta thresholds (change between serial troponin concentrations) increased sensitivity at the cost of a decreased percentage of patients below the delta threshold, with the largest changes at the greatest analytical variation. CONCLUSIONS: At the low-risk threshold, analytical variation up to 3â ng/L minimally impacted the safety metric (sensitivity) but marginally reduced effectiveness. Similarly, at the URL even relative variation up to 25% minimally impacted safety metrics and effectiveness. Analytical variation for delta thresholds did not negatively impact sensitivity but decreased effectiveness.
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Infarto do Miocárdio , Troponina I , Troponina T , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/sangue , Troponina T/sangue , Troponina I/sangueRESUMO
BACKGROUND: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States. METHODS: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants. A combined molecular and serologic assessment was used to determine the prevalence of SARS-CoV-2 infection. Vitamin D was examined as both a categorical (vitamin D status: deficient, insufficient, optimal) and continuous (vitamin D level) variable. Chi-squared testing, polynomial regression models, and logistic regression models were used to assess the relationship between vitamin D and SARS-CoV-2 infection. RESULTS: The overall SARS-CoV-2 infection rate among participants was 25.9%. Most participants were either vitamin D deficient (46.5%) or insufficient (29.7%), and 23.8% had an optimal level. Vitamin D status was significantly associated with key SARS-CoV-2 infection risk factors. As mean vitamin D levels increased, the proportion of participants with SARS-CoV-2 infection decreased. For every 10 ng/mL increase in vitamin D levels the odds of SARS-CoV-2 infection decreased by 12% when adjusting for race/ethnicity and age (main effect model). Participants who identified as Hispanic/Latino or Black non-Hispanic had approximately two times increased odds of SARS-CoV-2 infection when adjusting for age and vitamin D levels compared to white non-Hispanics. However, when additional factors were added to the main effect model, the relationship between vitamin D levels and SARS-CoV-2 infection did not remain significant. CONCLUSION: Vitamin D levels were associated with an increased risk of SARS-CoV-2 infection. Hispanic/Latino and Black, non-Hispanic compared to White, non-Hispanic participants were at increased odds for infection, after adjusting for race/ethnicity and age.
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COVID-19 , População Rural , SARS-CoV-2 , Deficiência de Vitamina D , Vitamina D , Humanos , COVID-19/epidemiologia , COVID-19/sangue , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Estados Unidos/epidemiologia , Grupos Minoritários/estatística & dados numéricos , Idoso , Prevalência , Adulto Jovem , Fatores de Risco , Área Carente de Assistência Médica , Estudos de CoortesRESUMO
BACKGROUND: The European Society of Cardiology (ESC) 0/1-h high sensitivity troponin T (hs-cTnT) algorithm does not differentiate risk based on known coronary artery disease (CAD: prior myocardial infarction [MI], coronary revascularization, or ≥ 70% coronary stenosis). We recently evaluated its performance among patients with known CAD at 30-days, but little is known about its longer-term risk prediction. The objective of this study is to determine and compare the performance of the algorithm at 90-days among patients with and without known CAD. METHODS: We performed a pre-planned subgroup analysis of the STOP-CP cohort, which prospectively enrolled ED patients ≥21 years old with symptoms suggestive of ACS without ST-elevation on initial ECG across 8 US sites (1/25/2017-9/6/2018). Participants with 0- and 1-h hs-cTnT measures (Roche, Basel, Switzerland) were stratified into rule-out, observe, and rule-in groups using the ESC 0/1-h algorithm. Algorithm performance was tested among patients with or without known CAD, as determined by the treating provider. The primary outcome was cardiac death or MI at 90-days. Fisher's exact tests were used to compare 90-day event and rule-out rates between patients with and without known CAD. Negative predictive values (NPVs) for 90-day cardiac death or MI with exact 95% confidence intervals were calculated and compared using Fisher's exact test. RESULTS: The STOP-CP study accrued 1430 patients, of which 31.4% (449/1430) had known CAD. Cardiac death or MI at 90 days was more common in patients with known CAD than in those without [21.2% (95/449) vs. 10.0% (98/981); p < 0.001]. Using the ESC 0/1-h algorithm, 39.6% (178/449) of patients with known CAD and 66.1% (648/981) of patients without known CAD were ruled-out (p < 0.001). Among rule-out patients, 90-day cardiac death or MI occurred in 3.4% (6/178) of patients with known CAD and 1.2% (8/648) without known CAD (p = 0.09). NPV for 90-day cardiac death or MI was 96.6% (95%CI 92.8-98.8) among patients with known CAD and 98.8% (95%CI 97.6-99.5) in patients without known CAD (p = 0.09). CONCLUSION: Patients with known CAD who were ruled-out using the ESC 0/1-h hs-cTnT algorithm had a high rate of missed 90-day cardiac events, suggesting that the ESC 0/1-h hs-cTnT algorithm may not be safe for use among patients with known CAD. TRIAL REGISTRATION: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436).
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Cardiologia , Doença da Artéria Coronariana , Humanos , Adulto Jovem , Adulto , Troponina T , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Estudos Prospectivos , Algoritmos , Morte , BiomarcadoresRESUMO
This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.
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COVID-19 , Vacinas , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/diagnóstico , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunoglobulina G , ImunoensaioRESUMO
BACKGROUND: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. METHODS: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. RESULTS: Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. CONCLUSIONS: Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.
Assuntos
Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/sangue , SARS-CoV-2/imunologia , Masculino , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Adulto , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Populações Vulneráveis/estatística & dados numéricos , População Rural/estatística & dados numéricos , Teste Sorológico para COVID-19/métodos , Teste Sorológico para COVID-19/estatística & dados numéricos , Idoso , Fosfoproteínas/imunologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Disparidades nos Níveis de SaúdeRESUMO
Objective: High sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). Methods: We studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. Results: Mean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). Conclusion: In US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.
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BACKGROUND: The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) 0/2-h algorithm is unclear among U.S. emergency department (ED) patients with acute chest pain. METHODS: A preplanned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 2-h hs-cTnT measures prospectively enrolled at eight U.S. EDs from January 2017 to September 2018 were stratified into rule-out, observation, and rule-in zones using the hs-cTnT 0/2-h algorithm alone and combined with the history, electrocardiogram, age, and risk factor (HEAR) score. The primary outcome was adjudicated 30-day cardiac death or myocardial infarction (CDMI). The sensitivity and negative predictive value (NPV) of the 0/2-h rule-out zone and specificity and positive predictive value (PPV) of the rule-in zone for 30-day CDMI were calculated. RESULTS: Of the 1307 patients accrued, 53.6% (700/1307) were male and 58.6% (762/1307) were White, with a mean ± SD age of 57.5 ± 12.7 years. At 30 days, CDMI occurred in 12.9% (168/1307) of participants. The 0/2-h algorithm ruled out 61.4% (802/1307) of patients. Among rule-out patients, 1.9% (15/802) experienced 30-day CDMI, resulting in a sensitivity of 91.1% (95% confidence interval [CI] 85.7%-94.9%) and NPV of 98.1% (95% CI 96.9%-98.9%). The 0/2-h algorithm ruled in 12.4% (162/1307) patients of whom 61.7% (100/162) experienced 30-day CDMI. The rule-in zone specificity was 94.6% (95% CI 93.1%-95.8%) and PPV was 61.7% (95% CI 53.8%-69.2%) for 30-day CDMI. The 0/2-h algorithm combined with HEAR score ruled out 30.7% (401/1307) of patients with a sensitivity and NPV for 30-day CDMI of 98.2% (95% CI 94.9%-99.6%) and 99.3% (95% CI 97.8%-99.8%), respectively. CONCLUSIONS: The hs-cTnT 0/2-h algorithm ruled out most patients. With NPV of <99% for 30-day CDMI, the hs-cTnT 0/2-h algorithm, many emergency physicians may not consider it safe to use for U.S. ED patients. When combined with a low-risk HEAR score, NPV was >99% for 30-day CDMI at the cost of reduced efficacy.
Assuntos
Infarto do Miocárdio , Troponina T , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Estudos de Coortes , Estudos Prospectivos , Fatores de Tempo , Infarto do Miocárdio/diagnóstico , Valor Preditivo dos Testes , Algoritmos , Serviço Hospitalar de Emergência , BiomarcadoresRESUMO
The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs <99% in each subgroup suggest the hs-cTnT ESC 0/1-h algorithm may not be safe for use in US EDs. Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436).
Assuntos
Cardiologia , Infarto do Miocárdio , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Troponina T , Estudos de Coortes , Fatores Raciais , Estudos Prospectivos , Infarto do Miocárdio/diagnóstico , Algoritmos , Morte , BiomarcadoresRESUMO
In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor.
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COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Química Clínica , SociedadesRESUMO
BACKGROUND: Artificial intelligence (AI) promises to become an important tool in the practice of laboratory medicine. AI programs are available online that can provide concise medical and laboratory information within seconds after a question is submitted. METHODS: We posed the following contemporary and relevant question for clinical chemists using an AI program: "Should labs eliminate CK-MB testing?" The results of this inquiry were critically reviewed by a cardiologist, emergency department physician, and clinical laboratorians for accuracy and appropriateness. RESULTS: An AI report answering this question was generated within 15 s. The experts felt that the information was inaccurate with the statements that CK-MB results are released earlier than cardiac troponin (cTn), and are more useful for detection of myocardial injury in patients with renal insufficiencies. The summary omitted discussion on the ongoing debate for periprocedural detection of acute myocardial infarction (MI), the perceived value for detection of reinfarction, the value in risk stratification compared to cTn, the economic justification for testing both CK-MB and cTn, and medicolegal aspects of testing when results are discordant. CONCLUSIONS: At this time, AI does not appear to be ready to be used by clinical laboratories for answering important practice questions.
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Serviços de Laboratório Clínico , Infarto do Miocárdio , Humanos , Inteligência Artificial , Laboratórios , Laboratórios Clínicos , Infarto do Miocárdio/diagnósticoAssuntos
Troponina T , Troponina , Humanos , Fatores de Risco , Biomarcadores , Valor Preditivo dos TestesRESUMO
The challenge of rapidly diagnosing myocardial ischemia in unstable angina (UA) patients presenting to the Emergency Department (ED) is due to a lack of sensitive blood biomarkers. This has prompted an investigation into microRNAs (miRNAs) related to cardiac-derived Nourin for potential diagnostic application. The Nourin protein is rapidly expressed in patients with acute coronary syndrome (ACS) (UA and acute myocardial infarction (AMI)). MicroRNAs regulate gene expression through mRNA binding and, thus, may represent potential biomarkers. We initially identified miR-137 and miR-106b and conducted a clinical validation, which demonstrated that they were highly upregulated in ACS patients, but not in healthy subjects and non-ACS controls. Using integrated comprehensive bioinformatics analysis, the present study confirms that the Nourin protein targets miR-137 and miR-106b, which are linked to myocardial ischemia and inflammation associated with ACS. Molecular docking demonstrated robust interactions between the Nourin protein and miR137/hsa-miR-106b, involving hydrogen bonds and hydrophobic interactions, with -10 kcal/mol binding energy. I-TASSER generated Nourin analogs, with the top 10 chosen for structural insights. Antigenic regions and MHCII epitopes within the Nourin SPGADGNGGEAMPGG sequence showed strong binding to HLA-DR/DQ alleles. The Cytoscape network revealed interactions of -miR137/hsa-miR--106b and Phosphatase and tensin homolog (PTEN) in myocardial ischemia. RNA Composer predicted the secondary structure of miR-106b. Schrödinger software identified key Nourin-RNA interactions critical for complex stability. The study identifies miR-137 and miR-106b as potential ACS diagnostic and therapeutic targets. This research underscores the potential of miRNAs targeting Nourin for precision ACS intervention. The analysis leverages RNA Composer, Schrödinger, and I-TASSER tools to explore interactions and structural insights. Robust Nourin-miRNA interactions are established, bolstering the case for miRNA-based interventions in ischemic injury. In conclusion, the study contributes to UA and AMI diagnosis strategies through bioinformatics-guided exploration of Nourin-targeting miRNAs. Supported by comprehensive molecular analysis, the hypoxia-induced miR-137 for cell apoptosis (a marker of cell damage) and the inflammation-induced miR-106b (a marker of inflammation) confirmed their potential clinical use as diagnostic biomarkers. This research reinforces the growing role of miR-137/hsa-miR-106b in the early diagnosis of myocardial ischemia in unstable angina patients.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , MicroRNAs , Infarto do Miocárdio , Humanos , Simulação de Acoplamento Molecular , MicroRNAs/metabolismo , Angina Instável/diagnóstico , Angina Instável/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Biomarcadores , Inflamação/metabolismoRESUMO
Importance: It is unclear to what extent insulin resistance is associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the general population after accounting for body composition. Objective: To characterize the association of insulin resistance with NT-proBNP independently of measures of body composition in US adults. Design, Setting, and Participants: In a cross-sectional design, data on participants aged 20 years or older were obtained from the 1999-2004 National Health and Nutrition Examination Survey with measures of NT-pro-BNP, body mass index (BMI), and dual energy x-ray absorptiometry (DEXA)-derived measures of body composition (fat and lean masses). Linear and logistic regression was used to characterize the associations of measures of body mass and composition (BMI, waist circumference, fat mass, and lean mass) with NT-proBNP, adjusting for cardiovascular risk factors. Linear regression was used to characterize the associations of homeostasis model assessment of insulin resistance [HOMA-IR] and NT-proBNP after adjusting for cardiovascular risk factors and body composition measures. The quantitative insulin sensitivity check index [QUICKI], triglyceride-glucose index [TyG index], insulin to glucose ratio [IGR], fasting insulin, and homeostasis model assessment of ß-cell function (HOMA-ß) were also examined. Data for this study were analyzed from August 10, 2022, to June 30, 2023. Main Outcomes and Measures: Adjusted changes in NT-proBNP by insulin resistance levels. Results: A total of 4038 adults without diabetes or cardiovascular disease were included (mean [SD] age, 44 years; 51.2% female; and 74.3% White). In sex-specific analyses, insulin resistance measures were inversely associated with NT-pro-BNP. After adjustment including cardiovascular risk factors, BMI, waist circumference, and DEXA-derived fat mass and lean mass, the percent change in NT-proBNP associated with an SD increase in HOMA-IR was -16.84% (95% CI, -21.23% to -12.21%) in women and -19.04% (95% CI, -24.14 to -13.59) in men. Similar associations were observed for other indices of insulin resistance, including QUICKI (women: 17.27; 95% CI, 10.92-23.99 vs men: 22.17; 95% CI, 15.27 to 29.48), TyG index women: -11.47; 95% CI, -16.12 to -6.57 vs men: -15.81; 95% CI, -20.40 to -10.95), IGR women: -15.15; 95% CI, -19.35 to -10.74 vs men: -16.61; 95% CI, -21.63 to -11.26), and fasting insulin (women: -16.32; 95% CI, -20.63 to -11.78 vs men: -18.22; 95% CI, -23.30 to -12.79), as well as HOMA-ß (women: -10.71; 95% CI, -14.71 to -6.52 vs men: -11.72; 95% CI, -16.35 to -6.85). Conclusions and Relevance: In a national sample of US adults, insulin resistance was inversely associated with NT-proBNP, even after rigorously accounting for multiple measures of fat mass and lean mass. These results suggest that the mechanisms linking NT-proBNP to insulin resistance are partially independent of excess adiposity and may be associated with hyperinsulinemia.
RESUMO
Objective: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is a marker of cardiac wall stress and is a predictor of cardiovascular disease. Higher diet quality is associated with lower risk of cardiovascular disease. The association between diet quality and subclinical cardiovascular disease assessed by NT-proBNP is uncharacterized. We investigated the associations between diet quality, using Healthy Eating Index-2015 (HEI-2015), and NT-proBNP from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Methods: We included 9,782 adults from NHANES 1999-2004 without self-reported cardiovascular disease. The HEI-2015 ranges from 0 to 100, with higher scores indicating better diet quality. The HEI-2015 was categorized into sex-specific quintiles. Regression models were used to quantify associations between the overall HEI-2015 score and its 13 components with log-transformed NT-proBNP. The beta coefficients were converted to percent differences. Results: Among 9,782 participants, mean age was 45 years, 48% were men, and 72% were non-Hispanic White adults. After adjusting for sociodemographic characteristics, lifestyle factors, and medical history, those in the highest vs. lowest HEI-2015 quintile had an 8.5% (95% CI: -14.6% to -2.0%) lower NT-proBNP level. There was a dose-response association between HEI-2015 and NT-proBNP (P value for trend = 0.01). Each 1-unit higher in sodium and added sugars score indicating lower intake was associated with lower NT-proBNP by 7.7% (95% CI: -12.8% to -2.2%) and 6.5% (95% CI: -12.0% to -0.7%), respectively. Conclusion: Higher diet quality, especially lower intakes of sodium and added sugars, was associated with lower serum levels of NT-proBNP.