Dries Testelmans

Bio: Dries Testelmans is an academic researcher from Katholieke Universiteit Leuven. The author has contributed to research in topics: Sleep apnea & Polysomnography. The author has an hindex of 22, co-authored 92 publications receiving 2100 citations. Previous affiliations of Dries Testelmans include Université catholique de Louvain & Bethesda Hospital.

A Novel Algorithm for the Automatic Detection of Sleep Apnea From Single-Lead ECG

Abstract: Goal: This paper presents a methodology for the automatic detection of sleep apnea from single-lead ECG. Methods: It uses two novel features derived from the ECG, and two well-known features in heart rate variability analysis, namely the standard deviation and the serial correlation coefficients of the RR interval time series. The first novel feature uses the principal components of the QRS complexes, and it describes changes in their morphology caused by an increased sympathetic activity during apnea. The second novel feature extracts the information shared between respiration and heart rate using orthogonal subspace projections. Respiratory information is derived from the ECG by means of three state-of-the-art algorithms, which are implemented and compared here. All features are used as input to a least-squares support vector machines classifier, using an RBF kernel. In total, 80 ECG recordings were included in the study. Results: Accuracies of about 85% are achieved on a minute-by-minute basis, for two independent datasets including both hypopneas and apneas together. Separation between apnea and normal recordings is achieved with 100% accuracy. In addition to apnea classification, the proposed methodology determines the contamination level of each ECG minute. Conclusion: The performances achieved are comparable with those reported in the literature for fully automated algorithms. Significance: These results indicate that the use of only ECG sensors can achieve good accuracies in the detection of sleep apnea. Moreover, the contamination level of each ECG segment can be used to automatically detect artefacts, and to highlight segments that require further visual inspection.

Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease.

Abstract: Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process.Objectives: To evaluate the presence of DC in small airways of patients with COPD.Methods: We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never-smokers, and smokers without COPD. Chemokine ligand 20 (CCL20, the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry.Measurements and Main Results: There is a significant increase in DC number in the epithelium (p = 0.007) and adventitia (p = 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventitia increases along with disease severi...

Increased duration of mechanical ventilation is associated with decreased diaphragmatic force: a prospective observational study

Abstract: Respiratory muscle weakness is an important risk factor for delayed weaning. Animal data show that mechanical ventilation itself can cause atrophy and weakness of the diaphragm, called ventilator-induced diaphragmatic dysfunction (VIDD). Transdiaphragmatic pressure after magnetic stimulation (TwPdi BAMPS) allows evaluation of diaphragm strength. We aimed to evaluate the repeatability of TwPdi BAMPS in critically ill, mechanically ventilated patients and to describe the relation between TwPdi and the duration of mechanical ventilation. This was a prospective observational study in critically ill and mechanically ventilated patients, admitted to the medical intensive care unit of a university hospital. Nineteen measurements were made in a total of 10 patients at various intervals after starting mechanical ventilation. In seven patients, measurements were made on two or more occasions, with a minimum interval of 24 hours. The TwPdi was 11.5 ± 3.9 cm H2O (mean ± SD), indicating severe respiratory muscle weakness. The between-occasion coefficient of variation of TwPdi was 9.7%, comparable with data from healthy volunteers. Increasing duration of mechanical ventilation was associated with a logarithmic decline in TwPdi (R = 0.69; P = 0.038). This association was also found for cumulative time on pressure control (R = 0.71; P = 0.03) and pressure-support ventilation (P = 0.05; R = 0.66) separately, as well as for cumulative dose of propofol (R = 0.66; P = 0.05) and piritramide (R = 0.79; P = 0.01). Duration of mechanical ventilation is associated with a logarithmic decline in diaphragmatic force, which is compatible with the concept of VIDD. The observed decline may also be due to other potentially contributing factors such as sedatives/analgesics, sepsis, or others.

Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep

Abstract: The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a "marker" of disease severity or a "mediator" of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation.

Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

Abstract: How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naive. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

Abstract: The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

Abstract: Background In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. Methods In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO 2 ) to the fraction of inspired oxygen (FiO 2 ) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. Results The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04), after adjustment for both the baseline PaO 2 :FIO 2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P = 0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. Conclusions In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique–Hopitaux de Marseille and the Programme Hospitalier de Recherche Clinique Regional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans.

Abstract: Background The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm. Methods We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). Case subjects had diaphragmatic inactivity and underwent mechanical ventilation for 18 to 69 hours; among control subjects diaphragmatic inactivity and mechanical ventilation were limited to 2 to 3 hours. We carried out histologic, biochemical, and gene-expression studies on these specimens. Results As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P = 0.001) and 53% (P = 0.01), respectively, decreased glutathione concentration of 23% (P = 0.01), increased active caspase-3 expression of 100% (P = 0.05), a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P = 0.002), and a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P = 0.001). Conclusions The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity.