Eosinophilia and fractional exhaled nitric oxide levels in chronic obstructive lung disease

IntroductionCOPD is a heterogeneous disorder with varied phenotypes. We aimed to determine the prevalence of asthma history, peripheral eosinophilia and elevated FeNO levels along with the diagnostic utility of peripheral eosinophilia in identifying airway eosinophilic inflammation.MethodsNational Health and Nutrition Examination Survey data were analysed for the study period 2007–2010. Subjects aged ≥40 years with postbronchodilator FEV1/FVC ratio <0.70 were included. Receiver operator curve analysis was performed for sensitivity analysis. A p value of <0.001 is considered statistically significant.ResultsA total of 3 110 617 weighted COPD cases were identified; predominantly male (64.4%) and non-Hispanic whites (86.1%). Among our COPD subjects, 14.6% had a history of doctor diagnosed asthma, highest among females and other race Americans. The overall prevalence of peripheral eosinophilia is 36%, 38.3% among COPD subjects with asthma history, and 35.6% among COPD without asthma history. The overall prevalence of elevated FeNO ≥25 ppb is 14.3%; 28.7% among COPD subjects with asthma history and 13.0% among COPD without asthma history.DiscussionThe prevalence of FeNO levels ≥25 ppb and peripheral eosinophilia was significantly higher among COPD subjects with asthma compared with COPD without asthma history. Not all COPD subjects with peripheral eosinophilia and elevated FeNO levels have a reported history of asthma. Our study supports clinically phenotyping COPD subjects with eosinophilic inflammation be independent of their asthma history and peripheral eosinophilia can be used as a surrogate marker in resource-limited settings.

Relationship of D-dimer and prediction of pulmonary embolism in hospitalized COVID-19 patients: a multicenter study

Aim: COVID-19 is a known risk factor for pulmonary embolism (PE). In this retrospective, multicenter study, we aimed to determine an optimal D-dimer cutoff to predict PE in hospitalized patients with COVID-19. Materials & methods: A total of 193 patients underwent computerized tomographic pulmonary angiography imaging and were classified into PE positive and negative groups. Physiological, radiological and biochemical parameters were compared and receiver operator curve analysis was conducted to determine a predictive D-dimer threshold. Results: An optimal D-dimer cutoff of 2494 ng/ml was selected (Youden index: 0.906), giving a sensitivity of 100% (95% CI: 100–100) and specificity of 90.62% (95% CI: 90.5–90.8) for predicting PE. Conclusion: We propose that in the absence of other clinical signs, a D-dimer threshold of 2495 ng/ml could be used with high sensitivity and specificity to predict PE in hospitalized patients with COVID-19.

Cerebral microbleed distribution following cardiac surgery can mimic cerebral amyloid angiopathy

Background and aimsHaving anecdotally noted a high frequency of lobar-restricted cerebral microbleeds (CMBs) mimicking cerebral amyloid angiopathy (CAA) in patients with previous cardiac surgery (especially valve replacement) presenting to our transient ischaemic attack (TIA) clinic, we set out to objectively determine the frequency and distribution of microbleeds in this population.MethodsWe performed a retrospective comparative cohort study in consecutive patients presenting to two TIA clinics with either: (1) previous coronary artery bypass grafting (CABG) (n=41); (2) previous valve replacement (n=41) or (3) probable CAA (n=41), as per the Modified Boston Criteria, without prior cardiac surgery. Microbleed number and distribution was determined and compared.ResultsAt least one lobar-restricted microbleed was found in the majority of cardiac surgery patients (65%) and 32/82 (39%) met diagnostic criteria for CAA. Valve replacement patients had a higher microbleed prevalence (90 vs 51%, p<0.01) and lobar-restricted microbleed count (2.6±2.7 vs 1.0±1.4, p<0.01) than post-CABG patients; lobar-restricted microbleed count in both groups was substantially less than in CAA patients (15.5±20.4, p<0.01). In postcardiac surgery patients, subcortical white matter (SWM) microbleeds were proportionally more frequent compared with CAA patients. Receiver operator curve analysis of a ‘location-based’ ratio (calculated as SWM/SWM+strictly-cortical CMBs), revealed an optimal ratio of 0.45 in distinguishing cardiac surgery-associated microbleeds from CAA (sensitivity 0.56, specificity 0.93, area under the curve 0.71).ConclusionLobar-restricted microbleeds are common in patients with past cardiac surgery, however a higher proportion of these CMBs involve the SWM than in patients with CAA.

Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

Predicting mortality in acute ischaemic stroke treated with mechanical thrombectomy: analysis of a multicentre prospective registry

ObjectivesWe aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT).DesignAnalysis of a multicentre prospective registry.SettingIn six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively.Participants224 patients with AIS were treated by MT.ResultsOf 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality.ConclusionsWe developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated.Trial registration numberChinese Clinical Trial Registry (ChiCTR-OOC-17013052).

A 10-fold and greater increase in D-dimer at admission in COVID-19 patients is highly predictive of pulmonary embolism in a retrospective cohort study

Background: COVID-19 patients present with both elevated D-dimer and a higher incidence of pulmonary embolism (PE). This single-centre retrospective observational study investigated the prevalence of early PE in COVID-19 patients and its relation to D-dimer at presentation. Methods: The study included 1038 COVID-19-positive patients, with 1222 emergency department (ED) attendances over 11 weeks (16 March to 31 May 2020). Computed tomography pulmonary angiogram (CTPA) for PE was performed in 123 patients within 48 h of ED presentation, of whom 118 had D-dimer results. The remaining 875 attendances had D-dimer performed. Results: CTPA performed in 11.8% of patients within 48 h of ED presentation confirmed PE in 37.4% (46/123). Thrombosis was observed at all levels of pulmonary vasculature with and without right ventricular strain. In the CTPA cohort, patients with PE had significantly higher D-dimer, prothrombin time, C-reactive protein, troponin, total bilirubin, neutrophils, white cell count and lower albumin compared with non-PE patients. However, there was no difference in the median duration of inpatient stay or mortality. A receiver operator curve analysis demonstrated that D-dimer could discriminate between PE and non-PE COVID-19 patients (area under the curve of 0.79, p < 0.0001). Furthermore, 43% ( n = 62/145) of patients with D-dimer >5000 ng/ml had CTPA with PE confirmed in 61% ( n = 38/62), that is, 26% of >5000 ng/ml cohort. The sensitivity and specificity were related to D-dimer level; cutoffs of 2000, 3000, 4000, and 5000 ng/ml, respectively, had a sensitivity of 93%, 90%, 90% and 86%, and a specificity of 38%, 54%, 59% and 68%, and if implemented, an additional 229, 141, 106 and 83 CTPAs would be required. Conclusion: Our data suggested an increased PE prevalence in COVID-19 patients attending ED with an elevated D-dimer, and patients with levels >5000 ng/ml might benefit from CTPA to exclude concomitant PE.

Differentiating combined pulmonary fibrosis and emphysema from pure emphysema: utility of late gadolinium-enhanced MRI

Background Differentiating combined pulmonary fibrosis with emphysema (CPFE) from pure emphysema can be challenging on high-resolution computed tomography (HRCT). This has antifibrotic therapy implications. Methods Twenty patients with suspected CPFE underwent late gadolinium-enhanced (LGE) thoracic magnetic resonance imaging (LGE-MRI) and HRCT. Data from twelve healthy control subjects from a previous study who underwent thoracic LGE-MRI were included for comparison. Quantitative LGE signal intensity (SI) was retrospectively compared in regions of fibrosis and emphysema in CPFE patients to similar lung regions in controls. Qualitative comparisons for the presence/extent of reticulation, honeycombing, and traction bronchiectasis between LGE-MRI and HRCT were assessed by two readers in consensus. Results There were significant quantitative differences in fibrosis SI compared to emphysema SI in CPFE patients (25.8, IQR 18.4–31.0 versus 5.3, IQR 5.0–8.1, p < 0.001). Significant differences were found between LGE-MRI and HRCT in the extent of reticulation (12.5, IQR 5.0–20.0 versus 25.0, IQR 15.0–26.3, p = 0.038) and honeycombing (5.0, IQR 0.0–10.0 versus 20.0, IQR 10.6–20.0, p = 0.001) but not traction bronchiectasis (10.0, IQR 5–15 versus 15.0, IQR 5–15, p = 0.878). Receiver operator curve analysis of fibrosis SI compared to similarly located regions in control subjects showed an area under the curve of 0.82 (p = 0.002). A SI cutoff of 19 yielded a sensitivity of 75% and specificity of 86% in differentiating fibrosis from similarly located regions in control subjects. Conclusion LGE-MRI can differentiate CPFE from pure emphysema and may be a useful adjunct test to HRCT in patients with suspected CPFE.

Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 μg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 μg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 μg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 μg/mL was 3.7 (95% CI, 1.1–13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

P119: Emergency department census is useful as a real-time measure of crowding

Introduction: Crowding is associated with poor patient outcomes in emergency departments (ED). Measures of crowding are often complex and resource-intensive to score and use in real-time. We evaluated single easily obtained variables to establish the presence of crowding compared to more complex crowding scores. Methods: Serial observations of patient flow were recorded in a tertiary Canadian ED. Single variables were evaluated including total number of patients in the ED (census), in beds, in the waiting room, in the treatment area waiting to be assessed, and total inpatient admissions. These were compared with Crowding scores (NEDOCS, EDWIN, ICMED, three regional hospital modifications of NEDOCS) as predictors of crowding. Predictive validity was compared to the reference standard of physician perception of crowding, using receiver operator curve analysis. Results: 144 of 169 potential events were recorded over 2 weeks. Crowding was present in 63.9% of the events. ED census (total number of patients in the ED) was strongly correlated with crowding (AUC = 0.82 with 95% CI = 0.76 - 0.89) and its performance was similar to that of NEDOCS (AUC = 0.80 with 95% CI = 0.76 - 0.90) and a more complex local modification of NEDOCS, the S-SAT (AUC = 0.83, 95% CI = 0.74 - 0.89). Conclusion: The single indicator, ED census was as predictive for the presence of crowding as more complex crowding scores. A two-stage approach to crowding intervention is proposed that first identifies crowding with a real-time ED census statistic followed by investigation of precipitating and modifiable factors. Real time signalling may permit more standardized and effective approaches to manage ED flow.

P2468Clinical and cardiac structural differences between paroxysmal and persistent/permanent non-valvular atrial fibrillation

Background Atrial Fibrillation (AF) is a heterogeneous condition and is traditionally classified by duration (paroxysmal, persistent and permanent). There is a relationship between AF and left atrial (LA) remodeling, with increased likelihood of AF recurrence and maintenance with increasing LA volumes. Purpose To assess clinical and cardiac structural differences between the subtypes of AF. Methods We examined 1247 (68±13.4y; 50% men) consecutive admissions presenting to our institution with the primary diagnosis of AF. Repeat admissions (n=263) were excluded. Of remaining 984 subjects, a majority had diagnosed paroxysmal (72.2%), with lower numbers of persistent (23.4%) and permanent (4.4%) AF. Echo parameters of cardiac chamber size and function were examined in a subset of subjects with complete echo (n=646) performed during incident hospital admission. Results There were significantly higher rates of diabetes mellitus (p=0.03), ischaemic heart disease (IHD; p=0.04) and peripheral vascular disease (PVD; p=0.02) in those with persistent/permanent AF compared to paroxysmal AF. No significant differences in age (p=0.19), BMI (p=0.42), OSA (p=0.05), or hypertension (p=0.76) was noted. There were significant differences in left ventricular (LV) mass and systolic function, LA size and function between the two groups (Table 1). Receiver operator curve analysis revealed that LAEF was a discriminator for persistent/permanent AF with an area under the curve of 0.689 (95% CI, 0.646 to 0.732; p<0.001). Echo parameters in AF subtype Echocardiographic Parameters Paroxysmal AF (n=433) Persistent and Permanent AF (n=213) Significance (p value) LVEDD (cm) 4.8±3.0 5.0±0.9 0.29 LVESD (cm) 3.3±1.3 3.7±1.1 <0.01 IVS thickness (cm) 1.2±0.7 1.1±0.3 0.44 PW thickness (cm) 1.1±0.7 1.1±0.2 0.77 LV mass (g) 92.3±28.3 108.2±35.3 <0.01 LVEF (%) 56.1±14.1 47.4±16.8 <0.01 LA Expansion Index 89.4±69.1 53.4±40.3 <0.01 Min LA Volume indexed (ml/m2) 18.9±17.2 27.3±20.6 0.01 Max LA Volume indexed (ml/m2) 32.5±19.2 37.7±15.3 <0.01 LAEF (%) 41.8±16.4 31.5±13.6 <0.01 Conclusions Our results suggest diabetes, IHD and PVD are associated with persistent/permanent AF. Additionally, greater LA remodeling and reduced atrial function was noted in this group, suggestive of an association between duration of AF electrical burden and LA remodeling and function.