Rileyklint9320
omes.While numerous studies have confirmed the prognostic role of high-sensitivity troponin T (hsTnT) in pulmonary embolism (PE), high-sensitivity troponin I (hsTnI) is inappropriately studied. This study aimed to investigate the prognostic relevance of hsTnI in normotensive PE, establish the optimal cut-off value for risk stratification and to compare the prognostic performances of hsTnI and hsTnT. Based on data from 459 consecutive PE patients enrolled in a single-centre registry, receiver operating characteristic analysis was used to identify an optimal hsTnI cut-off value for prediction of in-hospital adverse outcomes (PE-related death, cardiopulmonary resuscitation or vasopressor treatment) and all-cause mortality. Patients who suffered an in-hospital adverse outcome (4.8%) had higher hsTnI concentrations compared with those with a favourable clinical course (57 (interquartile range (IQR) 22-197) versus 15 (IQR 10-86) pg·mL-1, p=0.03). A hsTnI cut-off value of 16 ng·mL-1 provided optimal prognostic performance and predicted in-hospital adverse outcomes (OR 6.5, 95% CI 1.9-22.4) and all-cause mortality (OR 3.7, 95% CI 1.0-13.3). Between female and male patients, no relevant differences in hsTnI concentrations (17 (IQR 10-97) versus 17 (IQR 10-92) pg·mL-1, p=0.79) or optimised cut-off values were observed. Risk stratification according to the 2019 European Society of Cardiology algorithm revealed no differences if calculated based on either hsTnI or hsTnT (p=0.68). Our findings confirm the prognostic role of hsTnI in normotensive PE. HsTnI concentrations >16 pg·mL-1 predicted in-hospital adverse outcome and all-cause mortality; sex-specific cut-off values do not seem necessary. Importantly, our results suggest that hsTnI and hsTnT can be used interchangeably for risk stratification.A clinical case in a paediatric subject highlights the urgent requirement for cardiopulmonary exercise testing age-related reference values to be harmonised, to ensure appropriate clinical interpretation and patient management https//bit.ly/36WgOSO.
Although the pathophysiological mechanisms involved in the development of dyspnoea and poor exercise tolerance in patients with COPD are complex, dynamic lung hyperinflation (DLH) plays a central role. Diaphragmatic excursions can be measured by ultrasonography (US) with high intra- and interobserver reliability. The objective of this study was to evaluate the effect of diaphragmatic excursions as assessed by US on exercise tolerance and DLH in patients with COPD.
Patients with COPD (n=20) and age-matched control subjects (n=20) underwent US, which was used to determine the maximum level of diaphragmatic excursion (DE
). Ventilation parameters, including the change in inspiratory capacity (ΔIC), were measured in the subjects during cardiopulmonary exercise testing (CPET). We examined the correlations between DE
and the ventilation parameters.
The DE
of patients with COPD was significantly lower than that of the controls (45.0±12.8 mm
64.6±6.3 mm, respectively; p<0.01). The perception of peak dyspnoea (Borg scale) was significantly negatively correlated with DE
in patients with COPD. During CPET, oxygen uptake/weight (
'
/
) and minute ventilation (
'
) were significantly positively correlated with DE
, while
'
/
'
and
'
/carbon dioxide output (
'
) were significantly negatively correlated with DE
in patients with COPD. DE
was also significantly positively correlated with ΔIC, reflecting DLH, and with
'
/
, reflecting exercise capacity.
Reduced mobility of the diaphragm was related to decreased exercise capacity and increased dyspnoea due to dynamic lung hyperinflation in COPD patients.
Reduced mobility of the diaphragm was related to decreased exercise capacity and increased dyspnoea due to dynamic lung hyperinflation in COPD patients.α1-antitrypsin deficiency (AATD) is a rare and under-recognised genetic condition. Owing to its low prevalence, international initiatives are key for conducting high-quality research in the field. From July 2018 to December 2019, the European Alpha-1 Research Collaboration (EARCO) developed and conducted two surveys, one for healthcare providers and one for patients and caregivers, aiming to identify research priorities and barriers in access to treatment for AATD. A survey on 164 research questions was electronically sent to 230 AATD experts in Europe, and 94 completed surveys from 24 countries were received. The top research areas identified by healthcare providers were causes of variable progression and poor outcomes, improvement in diagnosis, initiation and optimal dosing of augmentation therapy and effectiveness of self-management interventions. During the same period, 438 surveys were completed by patients and caregivers from 26 countries. The top research areas identified were improving knowledge about AATD, in particular among general practitioners, access to AATD specialised centres and access to reliable, easy to understand information about living with AATD. Regarding barriers to treatment, participants from countries where augmentation therapy was reimbursed prioritised improving knowledge in AATD, while respondents in non-reimbursed countries regarded access to AATD augmentation therapy and to specialised centres as the most relevant. XL413 concentration The main research and management priorities identified by healthcare providers and patients included understanding the natural history of AATD, improving information to physicians, improving access to specialised reference centres, personalising treatment and having equal opportunities for access to existing therapies.The diagnosis of primary ciliary dyskinesia (PCD) relies on clinical features and sophisticated studies. The detection of bi-allelic disease-causing variants confirms the diagnosis. However, a standardised genetic panel is not widely available and new disease-causing genes are continuously identified. To assess the accuracy of untargeted whole-exome sequencing (WES) as a diagnostic tool for PCD, patients with symptoms highly suggestive of PCD were consecutively included. Patients underwent measurement of nasal nitric oxide (nNO) levels, ciliary transmission electron microscopy analysis (TEM) and WES. A confirmed PCD diagnosis in symptomatic patients was defined as a recognised ciliary ultrastructural defect on TEM and/or two pathogenic variants in a known PCD-causing gene. Forty-eight patients (46% male) were enrolled, with a median age of 10.0 years (range 1.0-37 years). In 36 patients (75%) a diagnosis of PCD was confirmed, of which 14 (39%) patients had normal TEM. A standalone untargeted WES had a diagnostic yield of 94%, identifying bi-allelic variants in 11 known PCD-causing genes in 34 subjects. A nNO less then 77 nL·min was nonspecific when including patients younger than 5 years (area under the receiver operating characteristic curve (AUC) 0.75, 95% CI 0.60-0.90). Consecutive WES considerably improved the diagnostic accuracy of nNO in young children (AUC 0.97, 95% CI 0.93-1). Finally, WES established an alternative diagnosis in four patients. In patients with clinically suspected PCD and low nNO levels, WES is a simple, beneficial and accurate next step to confirm the diagnosis of PCD or suggest an alternative diagnosis, especially in preschool-aged children in whom nNO is less specific.Molecular profiling of exhaled breath by electronic nose (eNose) might be suitable as a noninvasive tool that can help in monitoring of clinically unstable COPD patients. However, supporting data are still lacking. Therefore, as a first step, this study aimed to determine the accuracy of exhaled breath analysis by eNose to identify COPD patients who recently exacerbated, defined as an exacerbation in the previous 3 months. link2 Data for this exploratory, cross-sectional study were extracted from the multicentre BreathCloud cohort. Patients with a physician-reported diagnosis of COPD (n=364) on maintenance treatment were included in the analysis. Exacerbations were defined as a worsening of respiratory symptoms requiring treatment with oral corticosteroids, antibiotics or both. Data analysis involved eNose signal processing, ambient air correction and statistics based on principal component (PC) analysis followed by linear discriminant analysis (LDA). Before analysis, patients were randomly divided into a training (n=254) and validation (n=110) set. In the training set, LDA based on PCs 1-4 discriminated between patients with a recent exacerbation or no exacerbation with high accuracy (receiver operating characteristic (ROC)-area under the curve (AUC)=0.98, 95% CI 0.97-1.00). This high accuracy was confirmed in the validation set (AUC=0.98, 95% CI 0.94-1.00). link3 Smoking, health status score, use of inhaled corticosteroids or vital capacity did not influence these results. Exhaled breath analysis by eNose can discriminate with high accuracy between COPD patients who experienced an exacerbation within 3 months prior to measurement and those who did not. This suggests that COPD patients who recently exacerbated have their own exhaled molecular fingerprint that could be valuable for monitoring purposes.Severe hypereosinophilic asthma in children is extremely rare. This letter adds to the existing literature by providing long-term follow-up, and is the first report of the marked efficacy of benralizumab after failure of other biologic treatments. https//bit.ly/2G7Tc2k.The association between characteristics of sleep and physical activity in daily life (PADL) has not yet been investigated in depth in subjects with COPD. This study evaluated whether time spent per day in physical activity (PA) and sedentary behaviour are associated with sleep quantity and quality in this population. Sleep and PADL were objectively assessed by an activity monitor for 7 days and analysed on a minute-by-minute basis. Subjects also underwent spirometry and 6-min walking test (6MWT). Fifty-five subjects with moderate-to-severe COPD (28 male, 67±8 years) were studied. Subjects with total time in bed (TIB) per night ≥9 h had higher wake-after-sleep onset than TIB 7-9 h and TIB ≤7 h (195 (147-218) versus 117 (75-167) and 106 (84-156) min) and more fragmented sleep than TIB ≤7 h (8.2 (6.7-14.3) versus 6.3 (5.6-6.9) sleeping bouts; p less then 0.05 for all). Subjects with TIB ≥9 h also spent more time per day in sedentary behaviour and less time per day in PA of light and moderate-to-vigorous intensity than those with TIB 7-9 h and ≤7 h. In multiple linear regression, TIB ≥9 h was the only significant predictor of physical inactivity (β=-3.3 (-5.1, -1.6), p≤0.0001), accounting for 20% of its variation. Sleep fragmentation was frequent and more pronounced in physically inactive than active patients (7.5 (6.3-9.6) versus 6.4 (5.5-7.3) sleeping bouts; p=0.027). In summary, subjects with COPD with TIB ≥9 h·night-1 have more fragmented sleep, are more sedentary and less physically active than those with less then 9 h·night-1, independently of the awake time. Sleep quality is frequently poor and even worse in patients classified as physically inactive.The microcirculation comprising of arterioles, capillaries and post-capillary venules is the terminal vascular network of the systemic circulation. Microvascular homeostasis, comprising of a balance between vasoconstriction, vasodilation and endothelial permeability in healthy states, regulates tissue perfusion. In severe infections, systemic inflammation occurs irrespective of the infecting microorganism(s), resulting in microcirculatory dysregulation and dysfunction, which impairs tissue perfusion and often precedes end-organ failure. The common hallmarks of microvascular dysfunction in both septic shock and dengue shock, are endothelial cell activation, glycocalyx degradation and plasma leak through a disrupted endothelial barrier. Microvascular tone is also impaired by a reduced bioavailability of nitric oxide. In vitro and in vivo studies have however demonstrated that the nature and extent of microvascular dysfunction as well as responses to volume expansion resuscitation differ in these two clinical syndromes.
