Chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary ...disease (COPD). The process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. These adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient deficiency, osmolarity, low pH and antibiotic therapies. Phenotypic adaptations in bacterial pathogens from acute to chronic infection include, but are not limited to, antibiotic resistance, exopolysaccharide production (mucoidy), loss in motility, formation of small colony variants, increased mutation rate, quorum sensing and altered production of virulence factors associated with chronic infection. The evolution of Pseudomonas aeruginosa during chronic lung infection has been widely studied. More recently, the adaptations that other chronically colonising respiratory pathogens, including Staphylococcus aureus, Burkholderia cepacia complex and Haemophilus influenzae undergo during chronic infection have also been investigated. This review aims to examine the adaptations utilised by different bacterial pathogens to aid in their evolution from acute to chronic pathogens of the immunocompromised lung including CF and COPD.
Patients with chest pain comprise a large proportion of emergency presentations and place a major burden on healthcare resources. Therefore, efforts to safely and rapidly identify those with and ...without acute myocardial infarction (AMI) are needed. The challenge for clinicians is to accurately identify patients with acute coronary syndromes, while balancing the need to safely and rapidly reassure and discharge those without serious conditions.
This review summarizes the evidence to date on optimum accelerated strategies for the rule-in and rule-out of AMI, using strategies focused on optimum use of troponin results. Evidence based on both sensitive and highly sensitive troponin assay results is presented. The use of novel biomarkers is also addressed and the combination of biomarkers with other clinical information in accelerated diagnostic strategies is discussed.
The majority of patients, who are not at risk of myocardial infarction or other serious harm, may be suitable for discharge directly from the emergency setting using approaches focused on troponin algorithms and accelerated diagnostic protocols. Evidence about the clinical and health economic impact of use of such strategies is needed, as they may have major benefits for both patients and healthcare providers.
The new European Society of Cardiology guidelines to rule-in and rule-out acute myocardial infarction (AMI) in the emergency department include a rapid assessment algorithm based on high-sensitivity ...cardiac troponin and sampling at 0 and 1 hour. Emergency department physicians require high sensitivity to confidently rule-out AMI, whereas cardiologists aim to minimize false-positive results.
High-sensitivity troponin I and T assays were used to measure troponin concentrations in patients presenting with chest-pain symptoms and being investigated for possible acute coronary syndrome at hospitals in New Zealand, Australia, and Canada. AMI outcomes were independently adjudicated by at least 2 physicians. The European Society of Cardiology algorithm performance with each assay was assessed by the sensitivity and proportion with AMI ruled out and the positive predictive value and proportion ruled-in.
There were 2222 patients with serial high-sensitivity troponin T and high-sensitivity troponin I measurements. The high-sensitivity troponin T algorithm ruled out 1425 (64.1%) with a sensitivity of 97.1% (95% confidence interval CI, 94.0%-98.8%) and ruled-in 292 (13.1%) with a positive predictive value of 63.4% (95% CI, 57.5%-68.9%).The high-sensitivity troponin I algorithm ruled out 1205 (54.2%) with a sensitivity of 98.8% (95% CI, 96.4%-99.7%)) and ruled-in 310 (14.0%) with a positive predictive value of 68.1% (95% CI, 62.6%-73.2%).
The sensitivity of the European Society of Cardiology rapid assessment 0-/1-hour algorithm to rule-out AMI with high-sensitivity troponin may be insufficient for some emergency department physicians to confidently send patients home. These algorithms may prove useful to identify patients requiring expedited management. However, the positive predictive value was modest for both algorithms.
In practical terms, in preparation for the introduction of the sex- specific cutpoints at the New Zealand site a collaborative approach between pathologists, emergency physicians, and cardiologists ...developed a broad educational program with online support via the laboratory reporting system for interpretation of results. Author Contributions: All authors confirmed they have contributed to the intellectual content ofthispaper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition ofdata, or analysis and interpretation ofdata; (b) drafting or revising the article for intellectual content; and (c) final approval ofthe published article.
High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced ...performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol.
We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals.
Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 14.2%; 0/3-hour masked: 202/1632 12.4%;
=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 11.2%; 0/3-hour masked arm: 124/1486 8.3%;
=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 5.0% versus 0/3-hour: 62/1632 3.8%; hazard ratio, 1.32 95% CI, 0.95-1.83;
=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 3.7% versus 0/3-hour: 34/1486 2.3%; hazard ratio, 1.60 95% CI, 1.05-2.46;
=0.030).
Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.
Abstract
In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). ...Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality ‘high-flow nasal cannula’ seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique.
International guidelines to rule-in acute myocardial infarction (AMI) in patients presenting with chest pain to the emergency department (ED) recommend an algorithm using high-sensitivity cardiac ...troponin (hs-cTn) sampling on presentation and 3 h following presentation. We tested the diagnostic accuracy of this algorithm by pooling data from five distinct cohorts from three countries of prospectively recruited patients with independently adjudicated outcomes.
We measured high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) on presentation (0 h) and 3 h post-presentation samples in adult patients attending an ED with possible AMI to validate the European Society of Cardiology (ESC) Working Group on Acute Cardiac Care rule-in algorithm (ESC-rule-in). Specifically, (i) in patients with a 0 h hs-cTn concentration ≤99th percentile and a 3 h hs-cTn >99th percentile, positive patients are those with an absolute change in troponin ≥50% of the 99th percentile, and (ii) in patients with a 0 and 3 h hs-cTn >99th percentile, positive patients are those with a relative change in troponin of ≥20%. We concurrently assessed the efficacy of the 0 and 3 h hs-cTn <99th percentile to rule-out AMI.
1061 patients with hs-cTnI and 985 with hs-cTnT were included. The ESC-rule-in positive predictive value (PPV) was 83.5% (95% CI 74.9% to 90.1%) for hs-cTnI and 72.0% (95% CI 62.1% to 80.5%) for hs-cTnT. Forty-six AMIs (34.9%) were not ruled in using hs-cTnI and 62 (46.2%) using hs-cTnT. The sensitivity of the 99th percentile to rule-out AMI was 93.2% (95% CI 87.5% to 96.8%) for hs-cTnI and 94.8% (95% CI 89.5% to 97.9%) for hs-cTnT.
The ESC-rule-in algorithm has good PPV with hs-cTnI and reasonable with hs-cTnT and can rule-in over 50% of AMIs. However, the sensitivity of the 99th percentile to rule-out AMI is too low for clinical use.
Abstract Background High-sensitivity cardiac troponin (hs-cTn) may allow an earlier diagnosis of acute myocardial infarction (AMI). Methods We prospectively enrolled 1148 (derivation cohort) and 517 ...(external validation cohort) unselected patients presenting with suspected AMI to the emergency department. Final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnT was measured at presentation and after 2 hours. A diagnostic algorithm incorporating hs-cTnT values at presentation and absolute changes within the first 2 hours was derived. Results AMI was the final diagnosis in 16% of patients in the derivation and 9.1% in the validation cohort. The 2-hour algorithm developed in the derivation cohort classified 60% of patients as “rule-out,” 16% as “rule-in,” and 24% in the “observational-zone.” Resulting sensitivity and negative predictive value (NPV) were 99.5% and 99.9%, respectively, for rule-out, and specificity and positive predictive value (PPV) were 96% and 78%, respectively, for rule-in. Applying the 2-hour triage algorithm in the external validation cohort, 78% of patients could be classified as “rule-out,” 8% as “rule-in,” and 14% in the “observational-zone.” Resulting sensitivity and NPV were 96% and 99.5%, respectively, for rule-out, and specificity and PPV were 99% and 85%, respectively, for rule-in. Cumulative 30-day survival rates were 100%, 98.9%, and 95.2% ( P < .001), and 100%, 100%, and 95% ( P < .001) in patients classified as “rule-out,” “observational-zone,” and “rule-in” in the 2 cohorts, respectively. Conclusions A simple algorithm incorporating hs-cTnT baseline values and absolute changes over 2 hours allowed a triage toward safe rule-out, or accurate rule-in, of AMI in the vast majority of patients, with only 20% requiring more prolonged monitoring and serial blood sampling.
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