Broadening the Berlin definition of ARDS to patients receiving high-flow nasal oxygen:an observational study in patients with acute hypoxemic respiratory failure due to COVID-19

BACKGROUND: High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation.METHODS: We applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay.RESULTS: Of 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively.CONCLUSIONS: Using a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates.TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier NCT04719182).</p

Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging Implications for Vascular Interventional Studies

AbstractObjectivesThis study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies.Background18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available.Methods18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results.ResultsAll 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta.ConclusionsWe report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006

Current therapies for lowering lipoprotein (a)

Lipoprotein (a) [Lp(a)] is a human plasma lipoprotein with unique structural and functional characteristics. Lp(a) is an assembly of two components: a central core with apoB and an additional glycoprotein, called apo(a). Ever since the strong association between elevated levels of Lp(a) and an increased risk for CVD was recognized, interest in the therapeutic modulation of Lp(a) levels has increased. Here, the past and present therapies aiming to lower Lp(a) levels will be reviewed, demonstrating that these agents have had varying degrees of success. The next challenge will be to prove that Lp(a) lowering also leads to cardiovascular benefit in patients with elevated Lp(a) levels. Therefore, highly specific and potent Lp(a)-lowering strategies are awaited urgentl

Increased Systemic and Plaque Inflammation in ABCA1 Mutation Carriers With Attenuation by Statins

We previously demonstrated that subjects with functional ATP-binding cassette (ABC) A1 mutations have increased atherosclerosis, which has been attributed to the role of ABCA1 in reverse cholesterol transport. More recently, a proinflammatory effect of Abca1 deficiency was shown in mice, potentially contributing to atherogenesis. In this study, we investigated whether ABCA1 deficiency was associated with proinflammatory changes in humans. Thirty-one heterozygous, 5 homozygous ABCA1 mutation carriers, and 21 matched controls were studied. (18)Fluorodeoxyglucose positron emission tomography with computed tomographic scanning was performed in a subset of carriers and controls to assess arterial wall inflammation (target:background ratio). Heterozygous ABCA1 mutation carriers had a 20% higher target:background ratio than in controls (target:background ratio; P=0.008). In carriers using statins (n=7), target:background ratio was 21% reduced than in nonstatin users (n=7; P=0.03). We then measured plasma cytokine levels. Tumor necrosis factor α, monocyte chemoattractant protein-1, and interleukin-6 levels were increased in heterozygous and homozygous ABCA1 mutation carriers. We isolated monocytes from carriers and controls and measured inflammatory gene expression. Only TNFα mRNA was increased in monocytes from heterozygous ABCA1 mutation carriers. Additional studies in THP-1 macrophages showed that both ABCA1 deficiency and lipoprotein-deficient plasma from ABCA1 mutation carriers increased inflammatory gene expression. Our data suggest a proinflammatory state in ABCA1 mutation carriers as reflected by an increased positron emission tomography-MRI signal in nonstatin using subjects, and increased circulating cytokines. The increased inflammation in ABCA1 mutation carriers seems to be attenuated by statin

Analysing Tuberculosis Cases Among Healthcare Workers to Inform Infection Control Policy and Practices.

OBJECTIVE To determine the number and proportion of healthcare worker (HCW) tuberculosis (TB) cases infected while working in healthcare institutions in the Netherlands and to learn from circumstances that led to these infections. DESIGN Cohort analysis. METHODS We included all HCW TB patients reported to the Netherlands TB Register from 2000 to 2015. Using data from this register, including DNA fingerprints of the bacteria profile and additional information from public health clinics, HCW TB cases were classified into 4 categories: (1) infected during work in the Netherlands, (2) infected in the community, (3) infected outside the Netherlands, or (4) outside these 3 categories. An in-depth analysis of category 1 cases was performed to identify factors contributing to patient-to-HCW transmission. RESULTS In total, 131 HCW TB cases were identified: 32 cases (24%) in category 1; 13 cases (10%) in category 2; 42 cases (32%) in category 3; and 44 cases (34%) in category 4. The annual number of HCW TB cases (P<.05), the proportion among reported cases (P<.01), and the number of category 1 HCW TB cases (P=.12) all declined over the study period. Delayed diagnosis in a TB patient was the predominant underlying factor of nosocomial transmission in 47% of category 1 HCW TB patients, most of whom were subsequently identified in a contact investigation. Performing high-risk procedures was the main contributing factor in the other 53% of cases. CONCLUSION In low-incidence countries, every HCW TB case should warrant timely and thorough investigation to help further define and fine-tune the HCW screening policy and to monitor its proper implementation. Infect Control Hosp Epidemiol 2017;38:976-982