Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Awake Prone Positioning in COVID-19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single-center Retrospective Cohort Study.

BACKGROUND: Awake prone positioning has been widely used in patients with COVID-19 respiratory failure to avoid intubation despite limited evidence. Our objective was to evaluate if prone positioning is associated with a reduced intubation rate when compared to usual care. METHODS: This was a retrospective cohort study in the emergency department of a large quaternary hospital in Sao Paulo. We retrieved data from all admitted patients in need of oxygen supplementation (>3 L/min) and tachypnea (>24 ipm) from March 1 to April 30, 2020, excluding those who had any contraindication to the prone position or who had an immediate need for intubation. The primary endpoint was endotracheal intubation up to 15 days. Secondary outcomes included a 6-point clinical outcome ordinal scale, mechanical ventilation-free days, admission to the intensive care unit, and need of hemodialysis and of vasoactive drugs, all assessed at or up to 15 days. We analyzed unadjusted and adjusted effect estimates with Cox proportional hazards models, logistic regression, quantile regression, and sensitivity analyses using propensity score models. RESULTS: Of 925 suspected COVID-19 patients admitted off mechanical ventilation, 166 patients fulfilled inclusion and exclusion criteria: 57 were exposed to prone positioning and 109 to usual care. In the intervention group, 33 (58%) were intubated versus 53 (49%) in the control group. We observed no difference in intubation rates in the univariate analysis (hazard ratio = 1.21, 95% confidence interval [CI] = 0.78 to 1.88, p = 0.39) nor in the adjusted analysis (hazard ratio = 0.90, 95% CI = 0.55 to 1.49, p = 0.69). Results were robust to the sensitivity analyses. Secondary outcomes did not differ between groups. CONCLUSIONS: Awake prone positioning was not associated with lower intubation rates. Caution is necessary before widespread adoption of this technique, pending results of clinical trials.

Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19: A post-hoc analysis of a prospective cohort study

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Low educational status, smoking, and multidisciplinary team experience predict hospital length of stay after bariatric surgery.

OBJECTIVE: The objective of the present study was to identify new risk factors associated with longer hospitalization following bariatric surgery. METHODS: Patient clinical, social, and biochemical data in addition to multidisciplinary team experience were analyzed in a cohort that included all patients undergoing bariatric surgery at our hospital. The primary outcome was length of hospital stay (LOS). Mortality was recorded to validate the obesity surgery mortality risk score (OS-MRS). RESULTS: This study included 299 sequential patients, 41 ± 10 years of age, and BMI of 50 ± 8 kg/m(2) who underwent bariatric surgery. Two thirds (196) of patients were hypertensive, a third (86) were diabetic and a third (91) were current or former smokers. Overall, LOS was 8 ± 5 days. The predictors of a longer LOS were smoking (P < 0.05) and less multidisciplinary team experience (P < 0.05). Looking at only the last three years of data, LOS was 6 ± 5 days, and the predictors of a longer LOS were low educational attainment (P < 0.02) and smoking (P < 0.01) but not team experience. The global mortality was 2.6%, with the OS-MRS identifying a high-risk group. CONCLUSION: Excluding the initial learning phase, longer LOS independent predictors were patient low educational attainment and smoking. These predictors can help guide care to reduce complications.

Avaliação a médio prazo do controle de fatores de risco de doença cardiovascular em corte prospectiva de pacientes de alto risco tratados por intervenção coronária percutânea / Middle-term assessment of cardiovascular risk factor control in a prospective cohort of high-risk patients treated by percutaneous coronary intervention

INTRODUÇÃO: A prevenção secundária após intervenção coronária percutânea (ICP) é fundamental para melhorar a sobrevida livre de eventos e consiste principalmente no controle de fatores de risco. Analisou-se a prevenção secundária de pacientes de alto risco, incluídos prospectivamente no estudo Sequence Variation in Platelet Aggregation in Response to Clopidogrel and aspirin (SPARC). MÉTODOS: Foram arrolados 187 pacientes consecutivos entre dezembro de 2009 e fevereiro de 2011, tratados por ICP com stent e avaliados em retornos ambulatoriais de 30 dias, 3 meses, 6 meses e 12 meses quanto ao controle de hipertensão arterial, disglicemia, dislipidemia e tabagismo, e medidas terapêuticas respectivas. RESULTADOS: Houve aumento significativo de pacientes com controle pressórico (29%; P = 0,02), que cessaram tabagismo (18%; P = 0,003), e que receberam hipolipemiantes (19%; P < 0,0001) entre a internação para ICP e o primeiro retorno após o procedimento. Esse melhora do controle de fatores de risco refletiu-se em redução do escore de risco de Framingham médio observado no mesmo período (9,9%; P < 0,0001). Durante seguimento de até 12 meses o ganho atingido na internação para ICP se manteve para todos os fatores de risco. CONCLUSÕES: Observou-se efeito importante relativamente à internação índice para ICP, com aumento da prescrição de medicamentos para controle de fatores de risco e alcance de metas. Esse estudo identifica relevante janela de oportunidade para priorização do controle de fatores de risco na internação inicial, quando ganhos expressivos são observados e mantidos. Mas também explicita que esforços adicionais são necessários para expandir o benefício da prevenção secundária no seguimento a médio prazo de pacientes tratados por ICP.

BACKGROUND: Secondary prevention after percutaneous coronary intervention (PCI) is essential to increase event-free survival and consists mainly in risk factor control. We analyzed the secondary prevention of high-risk patients included prospectively in the Sequence Variation in Platelet Aggregation in Response to Clopidogrel and aspirin trial (SPARC). METHODS: From December 2009 to February 2011 we enrolled 187 consecutive patients who were submitted to PCI with stent implantation and were evaluated in outpatient visits at 1, 3, 6, and 12 months of follow-up for the control of hypertension, dysglycemia, hyperlipidemia and smoking and their respective therapeutic measures. RESULTS: There was a significant increa­se in the number of patients with controlled hypertension (29%; P = 0.02), who stopped smoking (18%; P = 0.003), and received statins (19%; P < 0.0001) between the index PCI and the first follow-up visit. The risk factor control improvement led to a decrease in the mean Framingham risk score (9.9%; P < 0.0001). During the 12 months follow-up the gains achieved at PCI admission were maintained for all risk factors. CONCLUSIONS: An important effect was observed on the index PCI admission with increased prescription of risk factor control drugs and achievement of therapeutic goals. This study identifies a relevant opportunity window for risk factor control at the index admission, when substantial gains are observed and maintained. However, it also shows further efforts are required to expand the benefit of secondary prevention in the middle-term follow-up of patients treated by PCI.

Specificity of modified Drosophila mariner transposons in the identification of Leishmania genes.

Genetic manipulation of the protozoan Leishmania has led to a better understanding of the survival and development of these pathogens within their hosts. The association of the Leishmania genome sequencing information with the ability of transposons to introduce or destroy phenotypes allows a global perspective on the role and importance of genes in cellular pathways. Herein we report the construction and testing of mariner transposable elements carrying the neomycin phosphotransferase, green fluorescent protein, or beta-glucuronidase genes as reporters for translational fusion events. We demonstrate that the expression of the reporter genes will occur only when the genes are inserted in-frame within predicted genes. Our results not only add to the mariner toolkit for gene manipulation but also strengthen the evidence that the mariner system is a reliable means for the study of gene expression in Leishmania.