Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

DESCRIPTION OF ESOPHAGOSTOMY TUBE PLACEMENT IN TWO GIANT ANTEATER (MYRMECOPHAGA TRIDACTYLA) CADAVERS.

Feeding of managed populations of giant anteater (Myrmecophaga tridactyla) is challenging in injured patients that present with anorexia. This report describes an approach for esophagostomy tube placement in this species. Cadavers of two adult giant anteaters were used for technique development. The animal was positioned in dorsal recumbency, and a guide feeding tube was inserted orally into the esophagus. A ventral midline incision in the midcervical region was made to access the esophagus and to protect submandibular salivary glands. The cervical musculature was dissected and retracted laterally to the right, the vagosympathetic nerve trunk was identified and preserved, and the esophagus was incised over the guide tube. The guide tube was removed to facilitate placement of the definitive tube, which was premeasured from its insertion point in the midcervical area to the level of the seventh-ninth intercostal space. The tube was secured to the cervical skin on the left side with a finger-trap suture.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Cost-Effectiveness Analysis of CCTA in SUS, as Compared to Other Non-Invasive Imaging Modalities in Suspected Obstructive CAD. / Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável.

BACKGROUND: The Brazilian public health system does not include computed tomography angiography (CTA). OBJECTIVE: Rank, according to the Brazilian public health system, the cost-effectiveness of different strategies for the diagnosis of coronary artery disease (CAD), combining exercise tests (ET), myocardial scintigraphy (MS), stress echocardiography (SE), and CTA in a hypothetical intermediate pre-test probability cohort of patients. METHODS: This study implemented a cost-effectiveness analysis through a decision tree. The incremental cost-effectiveness ratio (ICER) and net benefit were analyzed by adopting multiple thresholds of willingness to pay, from 0.05 to 1 GDP per capita per correct diagnosis. In sequential tests, a second confirmatory test was performed only when the first was positive. RESULTS: After excluding dominated or extended dominance diagnostic strategies, the efficiency frontier consisted of three strategies: ET, ET followed by SE, and SE followed by CTA, the last being the most cost-effective strategy. Through the net benefit, the ranking of the most cost-effective strategies varied according to willingness to pay. CONCLUSIONS: Using current concepts of health technology assessment, this study provides a ranking for decision-making concerning which diagnostic strategy to use in a population with an intermediate pre-test risk for CAD. With a feasible cost estimate adopted for CTA, the impact of including this to the list of the diagnostic arsenal would represent a cost-effective strategy in most of the evaluated scenarios with broad variations in the willingness to pay.

FUNDAMENTO: Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. OBJETIVOS: Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. MÉTODOS: Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. RESULTADOS: Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. CONCLUSÃO: Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

Real-time cardiac magnetic resonance cine imaging with sparse sampling and iterative reconstruction for left-ventricular measures: Comparison with gold-standard segmented steady-state free precession.

BACKGROUND: Segmented cine imaging with a steady-state free-precession sequence (Cine-SSFP) is currently the gold standard technique for measuring ventricular volumes and mass, but due to multi breath-hold (BH) requirements, it is prone to misalignment of consecutive slices, time consuming and dependent on respiratory capacity. Real-time cine avoids those limitations, but poor spatial and temporal resolution of conventional sequences has prevented its routine application. We sought to examine the accuracy and feasibility of a newly developed real-time sequence with aggressive under-sampling of k-space using sparse sampling and iterative reconstruction (Cine-RT). METHODS: Stacks of short-axis cines were acquired covering both ventricles in a 1.5T system using gold standard Cine-SSFP and Cine-RT. Acquisition parameters for Cine-SSFP were: acquisition matrix of 224×196, temporal resolution of 39ms, retrospective gating, with an average of 8 heartbeats per slice and 1-2 slices/BH. For Cine-RT: acquisition matrix of 224×196, sparse sampling net acceleration factor of 11.3, temporal resolution of 41ms, prospective gating, real-time acquisition of 1 heart-beat/slice and all slices in one BH. LV contours were drawn at end diastole and systole to derive LV volumes and mass. RESULTS: Forty-one consecutive patients (15 male; 41±17years) in sinus rhythm were successfully included. All images from Cine-SSFP and Cine-RT were considered to have excellent quality. Cine-RT-derived LV volumes and mass were slightly underestimated but strongly correlated with gold standard Cine-SSFP. Inter- and intra-observer analysis presented similar results between both sequences. CONCLUSIONS: Cine-RT featuring sparse sampling and iterative reconstruction can achieve spatial and temporal resolution equivalent to Cine-SSFP, providing excellent image quality, with similar precision measurements and highly correlated and only slightly underestimated volume and mass values.

Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável / Cost-Effectiveness Analysis of CCTA in SUS, as Compared to Other Non-Invasive Imaging Modalities in Suspected Obstructive CAD

Resumo Fundamento Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. Objetivos Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. Métodos Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. Resultados Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. Conclusão Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.

Abstract Background The Brazilian public health system does not include computed tomography angiography (CTA). Objective Rank, according to the Brazilian public health system, the cost-effectiveness of different strategies for the diagnosis of coronary artery disease (CAD), combining exercise tests (ET), myocardial scintigraphy (MS), stress echocardiography (SE), and CTA in a hypothetical intermediate pre-test probability cohort of patients. Methods This study implemented a cost-effectiveness analysis through a decision tree. The incremental cost-effectiveness ratio (ICER) and net benefit were analyzed by adopting multiple thresholds of willingness to pay, from 0.05 to 1 GDP per capita per correct diagnosis. In sequential tests, a second confirmatory test was performed only when the first was positive. Results After excluding dominated or extended dominance diagnostic strategies, the efficiency frontier consisted of three strategies: ET, ET followed by SE, and SE followed by CTA, the last being the most cost-effective strategy. Through the net benefit, the ranking of the most cost-effective strategies varied according to willingness to pay. Conclusions Using current concepts of health technology assessment, this study provides a ranking for decision-making concerning which diagnostic strategy to use in a population with an intermediate pre-test risk for CAD. With a feasible cost estimate adopted for CTA, the impact of including this to the list of the diagnostic arsenal would represent a cost-effective strategy in most of the evaluated scenarios with broad variations in the willingness to pay.

Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls.

Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* < 20 ms) in comparison with those without had significantly lower mean myocardial T1 times (868.9 ± 120.2 vs. 1170.3 ± 25.0 ms P = 0.005 respectively) and T2 times (34.9 ± 4.7 vs. 45.1 ± 2.0 ms P = 0.007 respectively). 3 T T1 and T2 times strongly correlated with 1.5 T, T2* times (Pearson's r = 0.95 and 0.91 respectively). T1 and T2 measures presented less variability than T2* in inter- and intra-observer analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification.