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Background : Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods : We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results : The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model {0.86 vs. 0.69, P

Background: Lung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes. Method: Prospective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume 2O, peak pressure 2O, peripheral oxygen saturation ≥88% and dynamic mechanical power Results: Forty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001). Conclusion: Among critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.

Background Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p

Background Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for cardiovascular disease but mechanisms underlying this association are incompletely understood. The speed of beat-to-beat changes in systolic blood pressure (vSBP) was found to be pronounced in patients with elevated cardiovascular risk. Although increased vSBP may thus be a contributing mechanism to cardiovascular morbidity, no data exist on vSBP in patients with COPD. Therefore, the purpose of this study was to evaluate whether there is an association between severity of COPD and vSBP. Methods Resting beat-to-beat blood pressure was recorded during 5min. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different inter-beat intervals (IBI). Univariate and multivariate analyses were performed to evaluate the association between forced expiratory volume in 1s (FEV 1 ) and vSBP. Results This study comprised 60 patients with COPD (24 females) with a mean [SD] FEV 1 of 45.4 [22.7] %predicted and 34 healthy controls. Short-term fluctuations in SBP were more pronounced in patients with COPD compared to healthy controls. There was a significant inverse correlation between FEV1 and vSBP ( r =−0.41, p =0.001). Even after adjustment for covariates in multivariate analysis, FEV1 was found to be independently associated with vSBP. Conclusions Patients with COPD are characterised by steeper blood pressure changes than healthy controls. The speed of fluctuations in SBP is associated with the severity of airflow limitation. Increased vSBP may be a mechanism underpinning the association between COPD and cardiovascular disease.

Preliminary evidence supports an association between obstructive sleep apnea (OSA) and thoracic aortic dilatation, although potential causative mechanisms are incompletely understood; these may include an increase in aortic wall transmural pressures, induced by obstructive apneas and hypopneas. In patients undergoing cardiac catheterization, mean blood pressure (MBP) in the thoracic aorta and esophageal pressure was simultaneously recorded by an indwelling aortic pigtail catheter and a balloon-tipped esophageal catheter in randomized order during: normal breathing, simulated obstructive hypopnea (inspiration through a threshold load), simulated obstructive apnea (Mueller maneuver), and end-expiratory central apnea. Aortic transmural pressure (aortic MBP minus esophageal pressure) was calculated. Ten patients with a median age (range) of 64 (46–75) yr were studied. Inspiration through a threshold load, Mueller maneuver, and end-expiratory central apnea was successfully performed and recorded in 10, 7, and 9 patients, respectively. The difference between aortic MBP and esophageal pressure (and thus the extra aortic dilatory force) was median (quartiles) +9.3 (5.4, 18.6) mmHg, P = 0.02 during inspiration through a threshold load, +16.3 (12.8, 19.4) mmHg, P = 0.02 during the Mueller maneuver, and +0.4 (−4.5, 4.8) mmHg, P = 0.80 during end-expiratory central apnea. Simulated obstructive apnea and hypopnea increase aortic wall dilatory transmural pressures because intra-aortic pressures fall less than esophageal pressures. Thus OSA may mechanically promote thoracic aortic dilatation and should be further investigated as a risk factor for the development or accelerated progression of thoracic aortic aneurysms.

Increased blood pressure variability (BPV), even in the absence of hypertension, has been identified as an important independent cardiovascular risk factor (CVRF). However, the role of the speed of changes in systolic blood pressure (SBP; vSBP) on cardiovascular risk needs to be investigated. The objective of this study was to investigate whether subjects with a high cardiovascular risk profile have an increased degree and speed of changes in SBP compared with subjects with low or no risk. Resting beat-to-beat blood pressure (BP) was recorded for 5 min. Standard BPV measures in both time and frequency domains were conducted. The s.d. of SBP (s.d.-SBP) values was used to quantify the degree of BPV. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different interbeat intervals (IBI). Subjects were allocated to one of four groups according to the number of CVRFs (0, 1, 2, ≥ 3 CVRF). Of 122 subjects, 19.7% had 0 CVRF, 27.0% had 1, 32.0% had 2 and 21.3% had ≥ 3 CVRFs. There was an increase in vSBP across the four risk groups. The vSBP in patients without CVRF was 3.12 (1.09), 1 CVRF 3.23 (1.07), 2 CVRF 4.16 (2.26) and ≥ 3 CVRF 4.22 (1.66; P = 0.015). The s.d.-SBP was not significantly different between the cardiovascular risk groups. The speed of fluctuations in SBP rather than the degree of BPV is pronounced in patients with elevated cardiovascular risk. Increased speed of BP fluctuations may thus be a contributing mechanism to cardiovascular morbidity.

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aimed to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxaemia and physical activity on endothelial function in COPD. In stable COPD patients, assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock score), airflow obstruction (forced expiratory volume in 1 s (FEV1)), systemic inflammation (high-sensitivity C-reactive protein and interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex sensitivity), hypoxaemia (arterial oxygen tension), hypercapnia (arterial carbon dioxide tension ( P aCO2)), physical activity (steps per day) and exercise capacity (6-min walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analyses. 106 patients (Global Initiative for Chronic Obstructive Lung Disease stage I/II 35%, stage III 25% and stage IV 40%) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (sex, smoking, combined inhaled long-acting β-adrenergic and steroid medication, heart rate, baroreflex sensitivity and P aCO2) and adjusted for potential confounders (cardiovascular risk and age). In addition, the FMD and FEV1 association was modified by physical activity. The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association. In COPD, the association between airflow obstruction and impaired endothelial function is modified by physical activity

Background: The incidence of thoracic aortic aneurysm (TAA) is estimated to be six to ten cases per 100,000 patient years. Sixty percent of TAA involve the ascending aorta (AA). Recent findings from observational studies suggest a possible link between obstructive sleep apnea (OSA), thoracic aortic dilatation and aortic events in patients with Marfan9s syndrome. Whether there is a high prevalence of thoracic aortic aneurysm in patients with OSA is currently unknown. Methods: Patients who underwent in-hospital respiratory polygraphy between 1996 and 2014 and had an echocardiography within the same year were included in this retrospective study. The diagnosis of TAA was defined by the following parameters: AA diameter > 42 mm for females and > 46 mm for males. OSA was defined as mild (apnoea-hypopnoea index (AHI) 5-15/h), moderate (AHI 30/h). Results: 206 patients were included in the analysis. 55 patients (27 %) had mild OSA, 48 patients (23 %) were diagnosed with moderate OSA and 77 patients (37 %) had severe OSA. TAA was identified in 63 of the 206 patients (31 %). The prevalence of TAA was significantly higher in patients with an AHI > 15/h (39 %) when compared to patients with no or mild OSA (21 %) (P=0.0072). Conclusion: This is the first study to determine a high prevalence of TAA in patients with moderate to severe OSA. Prospective controlled cohort studies are needed to investigate whether OSA is associated with faster progression of aortic dilatation and aortic events.

Double-lumen endotracheal tubes (DLTs), which are commonly used for single-lung ventilation during surgery, are difficult to insert. In addition, they often move during surgical lung manipulation which can cause life-threatening complications. Flexible bronchoscopy is used routinely to establish and confirm proper DLT placement. The newly designed VivaSight DLT has an integrated camera, allowing continuous visualization of its position in the trachea. We hypothesized that the time to intubation using the VivaSight DLT would be faster than with a conventional DLT. We enrolled 40 adults scheduled for thoracic surgery. Patients were randomized to conventional DLT (n = 20) or VivaSight DLT (n = 20). Time to intubation was our primary outcome. Secondary outcomes were insertion success without flexible bronchoscopy, frequency of tube displacement, ease of insertion, quality of lung collapse, postoperative complaints, and airway injuries. Time [mean (SD)] to successful intubation was significantly faster with the VivaSight DLT [63 (58) sec] compared with the conventional DLT [97 (84) sec; P = 0.03]. The VivaSight DLTs were correctly inserted during all attempts. When malpositioning of the VivaSight DLT occurred, it was easily remedied, even in the lateral position. The devices were comparable with respect to postoperative coughing, hoarseness, and sore throat. Airway injuries tended to be more common with the VivaSight DLT, although this study was underpowered for airway injuries. The VivaSight DLT camera allowed faster insertion and facilitated initial positioning. It also confirmed proper tube positioning intraoperatively and facilitated repositioning when necessary. This trial was registered at clinicaltrials.gov: NCT01807676.

Background: Altered cardiac repolarization and increased dispersion of repolarization have been identified as risk factors for sudden cardiac death (SCD). The prevalence of and the mechanisms contributing to altered cardiac repolarization are currently unknown in COPD. Methods: In 91 COPD patients, 32 controls matched for age, cardiovascular risk and medication, and 41 healthy subjects, measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) were derived from 12-lead electrocardiography (ECG). Prevalence rates of heart rate corrected QT (QTc) >450ms and QT dispersion >60ms were determined to assess the number of subjects at risk for SCD. Univariate and multivariate analyses were used to identify possible factors contributing to altered cardiac repolarization. Results: QTc was found to be prolonged in 31.9% and QT dispersion in 24.2% of the COPD patients compared to 12.5% in matched controls and 0% in healthy subjects. The QTc interval was longer in COPD patients compared to matched and healthy controls respectively (437.9 ± 29.5 vs. 420.1 ± 25.3 ms, p = 0.001 and vs. 413.4 ± 18.2 ms, p < 0.001). QT dispersion was significantly increased in COPD patients compared to healthy subjects (45.4 (34.8 , 59.5) vs. 39.7 (29.3 , 54.8) ms, p = 0.049). Only oxygen saturation was independently associated with QTc duration in multivariate analysis (β = -0.29, p = 0.015). Conclusion: One third of a typical COPD population has altered cardiac repolarization and increased dispersion of repolarization, which may be related to hypoxia. Altered cardiac repolarization may expose these patients to an increased risk for malignant ventricular arrhythmias and SCD., BMC Pulmonary Medicine, 14, ISSN:1471-2466

Background: It has been suggested that exhaled breath contains relevant information on health status. Objectives: We hypothesized that a novel mass spectrometry (MS) technique to analyze breath in real time could be useful to differentiate breathprints from chronic obstructive pulmonary disease (COPD) patients and controls (smokers and nonsmokers). Methods: We studied 61 participants including 25 COPD patients [Global Initiative for Obstructive Lung Disease (GOLD) stages I-IV], 25 nonsmoking controls and 11 smoking controls. We analyzed their breath by MS in real time. Raw mass spectra were then processed and statistically analyzed. Results: A panel of discriminating mass-spectral features was identified for COPD (all stages; n = 25) versus healthy nonsmokers (n = 25), COPD (all stages; n = 25) versus healthy smokers (n = 11) and mild COPD (GOLD stages I/II; n = 13) versus severe COPD (GOLD stages III/IV; n = 12). A blind classification (i.e. leave-one-out cross validation) resulted in 96% sensitivity and 72.7% specificity (COPD vs. smoking controls), 88% sensitivity and 92% specificity (COPD vs. nonsmoking controls) and 92.3% sensitivity and 83.3% specificity (GOLD I/II vs. GOLD III/IV). Acetone and indole were identified as two of the discriminating exhaled molecules. Conclusions: We conclude that real-time MS may be a useful technique to analyze and characterize the metabolome of exhaled breath. The acquisition of breathprints in a rapid manner may be valuable to support COPD diagnosis and to gain insight into the disease.

Preliminary evidence supports an association between OSA and cardiac dysrhythmias. Negative intrathoracic pressure, as occurring during OSA, may provoke cardiac dysrhythmias. Thus, we aimed to study the acute effects of simulated apnea and hypopnea on arrhythmic potential and measures of cardiac repolarization [QTC and T peak to T end intervals ( $$ T_{\text{p}} T_{{{\text{e}}_{\text{c}} }} $$ )] in humans. In 41 healthy volunteers, ECG was continuously recorded prior, during and after simulated obstructive hypopnea (inspiration through a threshold load), simulated apnea (Mueller maneuver), end-expiratory central apnea and normal breathing in randomized order. The number of subjects with premature beats was significantly higher during inspiration through a threshold load (n=7), and the Mueller maneuver (n=7) compared to normal breathing (n=0) (p=0.008 for all comparisons), but not during end-expiratory central apnea (n=3, p=0.125). Inspiration through a threshold load was associated with a non-significant mean (SD) increase of the QTC interval [+5.4 (22.4)ms, 95%CI −1.7 to +12.4ms, p=0.168] and a significant increase of the $$ T_{\text{p}} T_{{{\text{e}}_{\text{c}} }} $$ interval [+3.7 (8.9)ms, 95%CI +0.9 to +6.6ms, p=0.010]. The Mueller maneuver induced a significant increase of the QTC interval [+8.3 (23.4)ms, 95%CI 0.9 to +15.6ms, p=0.035] and the $$ T_{\text{p}} T_{{{\text{e}}_{\text{c}} }} $$ interval (+4.2 (8.2)ms, 95%CI +1.6 to +6.8ms, p=0.002). There were no significant changes of the QTC and $$ T_{\text{p}} T_{{{\text{e}}_{\text{c}} }} $$ intervals during central end-expiratory apnea. These data indicate that simulated obstructive apnea and hypopnea are associated with an increase of premature beats and prolongation of QTC and $$ T_{\text{p}} T_{{{\text{e}}_{\text{c}} }} $$ intervals. Therefore, negative intrathoracic pressure changes may be a contributory mechanism for the association between OSA and cardiac dysrhythmias

BackgroundObjectively measuring daily physical activity (PA) using an accelerometer is a relatively expensive and time-consuming undertaking. In routine clinical practice it would be useful to estimate PA in patients with chronic obstructive pulmonary disease (COPD) with more simple methods.ObjectivesTo evaluate whether PA can be estimated by simple tests commonly used in clinical practice in patients with COPD.MethodsThe average number of steps per day was measured for 7 days with a SenseWear Pro™ accelerometer and used as gold standard for PA. A physical activity level (PAL) of ResultsIn 70 patients with COPD (21 females) with a mean [SD] FEV(1) of 43.0 [22.0] %predicted, PA was found to be significantly and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80, pConclusionsIn patients with COPD simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the Zutphen Physical Activity Questionnaire cannot be used to reliably predict physical inactivity.

AIMS: The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA. METHODS AND RESULTS: Forty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QT(c), TpTe(c) intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QT(c) and TpTe(c) intervals (mean difference between groups 21.4 ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95% CI 0.00-0.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QT(c) interval and the TpTe(c) interval (r = 0.60, 95% CI 0.36-0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively). CONCLUSION: Continuous positive airway pressure withdrawal is associated with the prolongation of the QT(c) and TpTe(c) intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac death.