Objectives
Guidelines recommend chest radiography (CR) in the workup of suspected acute aortic syndromes (AASs) if the pretest clinical probability is low. However, the diagnostic impact of CR ...integration for the rule‐in and rule‐out of AASs is unknown.
Methods
We performed a secondary analysis of the ADvISED multicenter study. Emergency department outpatients were eligible if an AAS was clinically suspected. Clinical probability was defined with the aortic dissection detection risk score (ADD‐RS). CR was evaluated blindly by a radiologist, who judged on mediastinum enlargement (ME) and other signs.
Results
In 2014 through 2016, a total of 1,129 patients were enrolled and 1,030 were analyzed, including 48 (4.7%) with AASs. ADD‐RS/ME and ADD‐RS/any CR sign (aCRs) integration were more accurate than ADD‐RS alone (area under the curve = 0.8 and 0.78 vs. 0.66, p < 0.001). The sensitivity and specificity of the integrated strategies were 66.7% (95% confidence interval CI = 51.5% to 79.9%) and 82.5% (95% CI = 79.9% to 84.8%) for ADD‐RS/ME and 68.8% (95% CI = 53.6% to 80.9%) and 76.5% (95% CI = 73.7% to 79.1%) for ADD‐RS/aCRs, respectively. The sensitivity and specificity of CR per se were 54.2% (95% CI = 39.2% to 68.6%) and 92.4% (95% CI = 90.5% to 93.9%) for ME and 60.4% (95% CI = 45.3% to 74.2%) and 85.2% (95% CI = 82.9% to 87.4%) for aCRs. The agreement (κ) between attending physicians and radiologists for ME was 0.44 (95% CI = 0.35 to 0.54). ADD‐RS/ME rule‐in (ADD‐RS ≤ 1 and ME‐present, or ADD‐RS > 1) applied to 204 versus 130 patients with ADD‐RS > 1, including 14 with AAS and 60 false‐positives (FP). ADD‐RS/aCRs rule‐in (ADD‐RS ≤ 1 and aCRs‐present, or ADD‐RS > 1) applied to 264 patients, including 15 with AAS and 119 FP. ADD‐RS/ME rule‐out (ADD‐RS ≤ 1 and ME‐absent) applied to 826 (80.2%) patients, including 16 with AAS (33.3% of cases). ADD‐RS/aCRs rule‐out (ADD‐RS ≤ 1 and aCRs‐absent) applied to 766 patients (74.4%), including 15 with AAS (31.3% of cases).
Conclusions
CR integration with clinical probability assessment showed modest rule‐in efficiency and insufficient sensitivity for conclusive rule‐out.
Background When acute aortic syndromes (AASs) are suspected, pretest clinical probability assessment and d-dimer (DD) testing are diagnostic options allowing standardized care. Guidelines suggest use ...of a 12-item/3-category score (aortic dissection detection) and a DD cutoff of 500 ng/mL. However, a simplified assessment tool and a more specific DD cutoff could be advantageous. Methods and Results In a prospective derivation cohort (n=1848), 6 items identified by logistic regression (thoracic aortic aneurysm, severe pain, sudden pain, pulse deficit, neurologic deficit, hypotension), composed a simplified score (AORTAs) assigning 2 points to hypotension and 1 to the other items. AORTAs≤1 and ≥2 defined low and high clinical probability, respectively. Age-adjusted DD was calculated as years/age × 10 ng/mL (minimum 500). The AORTAs score and AORTAs≤1/age-adjusted DD rule were validated in 2 patient cohorts: a high-prevalence retrospective cohort (n=1035; 22% AASs) and a low-prevalence prospective cohort (n=447; 11% AASs) subjected to 30-day follow-up. The AUC of the AORTAs score was 0.729 versus 0.697 of the aortic dissection detection score (
=0.005). AORTAs score assessment reclassified 16.6% to 25.1% of patients, with significant net reclassification improvement of 10.3% to 32.7% for AASs and -8.6 to -17% for alternative diagnoses. In both cohorts, AORTAs≥2 had superior sensitivity and slightly lower specificity than aortic dissection detection ≥2. In the prospective validation cohort, AORTAs≤1/age-adjusted DD had a sensitivity of 100%, a specificity of 48.6%, and an efficiency of 43.3%. Conclusions AORTAs is a simplified score with increased sensitivity, improved AAS classification, and minor trade-off in specificity, amenable to integration with age-adjusted DD for diagnostic rule-out.
The clinical utility of procalcitonin in the diagnosis and management of pneumonia remains controversial.
We assessed the clinical utility of procalcitonin in 2 prospective studies: first, a ...multicenter diagnostic study in patients presenting to the emergency department with acute dyspnea to directly compare the diagnostic accuracy of procalcitonin with that of interleukin 6 and C-reactive protein (CRP) in the diagnosis of pneumonia; second, a randomized management study of procalcitonin guidance in patients with acute heart failure and suspected pneumonia. Diagnostic accuracy for pneumonia as centrally adjudicated by 2 independent experts was quantified with the area under the ROC curve (AUC).
Among 690 patients in the diagnostic study, 178 (25.8%) had an adjudicated final diagnosis of pneumonia. Procalcitonin, interleukin 6, and CRP were significantly higher in patients with pneumonia than in those without. When compared to procalcitonin (AUC = 0.75; 95% CI, 0.71-0.78), interleukin 6 (AUC = 0.80; 95% CI, 0.77-0.83) and CRP (AUC = 0.82; 95% CI, 0.79-0.85) had significantly higher diagnostic accuracy (
= 0.010 and
< 0.001, respectively). The management study was stopped early owing to the unexpectedly low AUC of procalcitonin in the diagnostic study. Among 45 randomized patients, the number of days on antibiotic therapy and the length of hospital stay were similar (both
= 0.39) in patients randomized to the procalcitonin-guided group (n = 25) and usual-care group (n = 20).
In patients presenting with dyspnea, diagnostic accuracy of procalcitonin for pneumonia is only moderate and lower than that of interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected.
Pneumonia has diverse and often unspecific symptoms. As the role of biomarkers in the diagnosis of pneumonia remains controversial, it is often difficult to distinguish pneumonia from other illnesses causing shortness of breath. The current study prospectively enrolled unselected patients presenting with acute dyspnea and directly compared the diagnostic accuracy of procalcitonin, interleukin 6, and CRP for the diagnosis of pneumonia. In this setting, diagnostic accuracy of procalcitonin for pneumonia was lower as compared to interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected.
NCT01831115.
•We explore cardiac/inflammatory biomarkers to predict in-hospital mortality in endocarditis.•Troponin concentration measured at admission showed the highest accuracy for mortality ...prediction.•Inflammatory biomarkers had better accuracy at the 7th day than at admission.
Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE.
Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality.
Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8–6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4–5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3–3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1–3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1–2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0–3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759).
S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.
Introduction
The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to ...evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients.
Material and methods
This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction.
Results
The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858–0.982,
p
= 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046–1.325,
p
= 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031–1.334,
p
= 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022–1.524,
p
= 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed.
Conclusion
Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.
Abstract Background Pre-clinical trials have demonstrated that, during intravenous microbubble infusion, high mechanical index (HMI) impulses from a diagnostic ultrasound (DUS) transducer might ...restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). Objectives The purpose of this study was to test the safety and efficacy of this adjunctive approach in humans. Methods From May 2014 through September 2015, patients arriving with their first STEMI were randomized to either DUS intermittent HMI impulses (n = 20) just prior to emergent percutaneous coronary intervention (PCI) and for an additional 30 min post-PCI (HMI + PCI), or low mechanical index (LMI) imaging only (n = 10) for perfusion assessments before and after PCI (LMI + PCI). All studies were conducted during an intravenous perflutren lipid microsphere infusion. A control reference group (n = 70) arrived outside of the time window of ultrasound availability and received emergent PCI alone (PCI only). Initial epicardial recanalization rates prior to emergent PCI and improvements in microvascular flow were compared between ultrasound-treated groups. Results Median door-to-dilation times were 82 ± 26 min in the LMI + PCI group, 72 ± 15 min in the HMI + PCI group, and 103 ± 42 min in the PCI-only group (p = NS). Angiographic recanalization prior to PCI was seen in 12 of 20 HMI + PCI patients (60%) compared with 10% of LMI + PCI and 23% of PCI-only patients (p = 0.002). There were no differences in microvascular obstructed segments prior to treatment, but there were significantly smaller proportions of obstructed segments in the HMI + PCI group at 1 month (p = 0.001) and significant improvements in left ventricular ejection fraction (p < 0.005). Conclusions HMI impulses from a diagnostic transducer, combined with a commercial microbubble infusion, can prevent microvascular obstruction and improve functional outcome when added to the contemporary PCI management of acute STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330 )
The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates’ drugs. Nitazoxanide (NTZ) has a broad antiviral effect.
This was a randomized, double-blind pilot ...clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used.
Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01)
Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.
Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for ...index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications.
This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding.
In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units).
Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range IQR: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003).
A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267)
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