Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation

Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.This work was funded by projects PI16/01606, integrated in the Plan Nacional de R+D+I and co-funded by the ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). RTC-2017-6193-1 (AEI/FEDER UE). CIBER Enfermedades Respiratorias, and Fundació Parc Taulí

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

In vivo 5-flourouracil-induced apoptosis on murine thymocytes: Involvement of FAS, Bax and Caspase3

Apoptosis is a highly regulated and programmed cell breakdown process characterized by numerous changes. It was reported as the major mechanism of anticancer drug-induced cells death. Unfortunately, many of these drugs are non-specific and cause severe side effects. The effects of 5-fluorouracil (5-FU) on the apoptotic events in normal murine thymus were evaluated using an in vivo model. A single dose of 5-FU (150 mg/kg ip) was injected to CF-1 mice. A multiparametric analysis of thymic weight, cellularity, viability, architectural organization, apoptosis, DNA fragmentation, and the expression of several apoptotic proteins was evaluated in 10 days time-course study post-5-FU dosing. Total organ weights, thymocyte counts, and cell viabilities diminished drastically from the second day. The thymus architecture assessed through electron scanning microscopy revealed deep alterations and the lost of cell-cell contact between the first and the third days. DNA fragmentation and apoptotic indexes (May Grünwald Giemsa staining, double fluorescent dyes, and TdT-mediated dUTP nick-end labeling assay) revealed that cell death was maximal on the second day (three times over control). Furthermore, the pro-apoptotic proteins FAS and Bax were strongly up-regulated during the first 2 days. The aforementioned morphological and biochemical changes were also accompanied within the same period by caspase 3 activation. This study revealed that in vivo apoptosis in normal thymus after 5-FU administration is related to FAS, Bax, and Caspase 3 co-expressions under the current experimental conditions, these findings, therefore, contribute to a new insight into the molecular mechanisms involved during 5-FU administration upon the thymus and the possible events committed in the lymphophenia associated with chemotherapy.Fil: Aquino Esperanza, Jose A.. Universidad Nacional del Nordeste. Facultad de Medicina; ArgentinaFil: Aguirre, María Victoria. Universidad Nacional del Nordeste. Facultad de Medicina; ArgentinaFil: Aispuru, Gualberto R.. Universidad Nacional del Nordeste. Facultad de Medicina; ArgentinaFil: Lettieri, Carolina N.. Universidad Nacional del Nordeste. Facultad de Medicina; ArgentinaFil: Juaristi, Julian Antonio. Universidad Nacional del Nordeste. Facultad de Medicina; ArgentinaFil: Alvarez, Mirta Alba. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Brandan, Nora Cristina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

Cognitive phenotypes 1 month after ICU discharge in mechanically ventilated patients : a prospective observational cohort study

ICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored. A total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment. K-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n = 13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n = 33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n = 46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p = 0.016) and doses (p = 0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p = 0.001) than in K1 or K3. Cognitive reserve was significantly (p = 0.001) higher in K3 than in K1 or K2. One month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients. ClinicalTrials.gov Identifier:NCT02390024; March 17,2015

Soil macroinvertebrate communities: A world‐wide assessment

International audienceAim: Macroinvertebrates comprise a highly diverse set of taxa with great potential as indicators of soil quality. Communities were sampled at 3,694 sites distributed world-wide. We aimed to analyse the patterns of abundance, composition and network characteristics and their relationships to latitude, mean annual temperature and rainfall, land cover, soil texture and agricultural practices. Location: Sites are distributed in 41 countries, ranging from 55 degrees S to 57 degrees N latitude, from 0 to 4,000 m in elevation, with annual rainfall ranging from 500 to >3,000 mm and mean temperatures of 5-32 degrees C. Time period: 1980-2018. Major taxa studied: All soil macroinvertebrates: Haplotaxida; Coleoptera; Formicidae; Arachnida; Chilopoda; Diplopoda; Diptera; Isoptera; Isopoda; Homoptera; Hemiptera; Gastropoda; Blattaria; Orthoptera; Lepidoptera; Dermaptera; and "others". Methods: Standard ISO 23611-5 sampling protocol was applied at all sites. Data treatment used a set of multivariate analyses, principal components analysis (PCA) on macrofauna data transformed by Hellinger's method, multiple correspondence analysis for environmental data (latitude, elevation, temperature and average annual rainfall, type of vegetation cover) transformed into discrete classes, coinertia analysis to compare these two data sets, and bias-corrected and accelerated bootstrap tests to evaluate the part of the variance of the macrofauna data attributable to each of the environmental factors. Network analysis was performed. Each pairwise association of taxonomic units was tested against a null model considering local and regional scales, in order to avoid spurious correlations. Results: Communities were separated into five clusters reflecting their densities and taxonomic richness. They were significantly influenced by climatic conditions, soil texture and vegetation cover. Abundance and diversity, highest in tropical forests (1,895 +/- 234 individuals/m(2)) and savannahs (1,796 +/- 72 individuals/m(2)), progressively decreased in tropical cropping systems (tree-associated crops, 1,358 +/- 120 individuals/m(2); pastures, 1,178 +/- 154 individuals/m(2); and annual crops, 867 +/- 62 individuals/m(2)), temperate grasslands (529 +/- 60 individuals/m(2)), forests (232 +/- 20 individuals/m(2)) and annual crops (231 +/- 24 individuals/m(2)) and temperate dry forests and shrubs (195 +/- 11 individuals/m(2)). Agricultural management decreased overall abundance by <= 54% in tropical areas and 64% in temperate areas. Connectivity varied with taxa, with dominant positive connections in litter transformers and negative connections with ecosystem engineers and Arachnida. Connectivity and modularity were higher in communities with low abundance and taxonomic richness. Main conclusions: Soil macroinvertebrate communities respond to climatic, soil and land-cover conditions. All taxa, except termites, are found everywhere, and communities from the five clusters cover a wide range of geographical and environmental conditions. Agricultural practices significantly decrease abundance, although the presence of tree components alleviates this effect

Soil macroinvertebrate communities: A world‐wide assessment

International audienceAim Macroinvertebrates comprise a highly diverse set of taxa with great potential as indicators of soil quality. Communities were sampled at 3,694 sites distributed world-wide. We aimed to analyse the patterns of abundance, composition and network characteristics and their relationships to latitude, mean annual temperature and rainfall, land cover, soil texture and agricultural practices. Location Sites are distributed in 41 countries, ranging from 55 degrees S to 57 degrees N latitude, from 0 to 4,000 m in elevation, with annual rainfall ranging from 500 to >3,000 mm and mean temperatures of 5-32 degrees C. Time period 1980-2018. Major taxa studied All soil macroinvertebrates: Haplotaxida; Coleoptera; Formicidae; Arachnida; Chilopoda; Diplopoda; Diptera; Isoptera; Isopoda; Homoptera; Hemiptera; Gastropoda; Blattaria; Orthoptera; Lepidoptera; Dermaptera; and "others". Methods Standard ISO 23611-5 sampling protocol was applied at all sites. Data treatment used a set of multivariate analyses, principal components analysis (PCA) on macrofauna data transformed by Hellinger's method, multiple correspondence analysis for environmental data (latitude, elevation, temperature and average annual rainfall, type of vegetation cover) transformed into discrete classes, coinertia analysis to compare these two data sets, and bias-corrected and accelerated bootstrap tests to evaluate the part of the variance of the macrofauna data attributable to each of the environmental factors. Network analysis was performed. Each pairwise association of taxonomic units was tested against a null model considering local and regional scales, in order to avoid spurious correlations. Results Communities were separated into five clusters reflecting their densities and taxonomic richness. They were significantly influenced by climatic conditions, soil texture and vegetation cover. Abundance and diversity, highest in tropical forests (1,895 +/- 234 individuals/m(2)) and savannahs (1,796 +/- 72 individuals/m(2)), progressively decreased in tropical cropping systems (tree-associated crops, 1,358 +/- 120 individuals/m(2); pastures, 1,178 +/- 154 individuals/m(2); and annual crops, 867 +/- 62 individuals/m(2)), temperate grasslands (529 +/- 60 individuals/m(2)), forests (232 +/- 20 individuals/m(2)) and annual crops (231 +/- 24 individuals/m(2)) and temperate dry forests and shrubs (195 +/- 11 individuals/m(2)). Agricultural management decreased overall abundance by <= 54% in tropical areas and 64% in temperate areas. Connectivity varied with taxa, with dominant positive connections in litter transformers and negative connections with ecosystem engineers and Arachnida. Connectivity and modularity were higher in communities with low abundance and taxonomic richness. Main conclusions Soil macroinvertebrate communities respond to climatic, soil and land-cover conditions. All taxa, except termites, are found everywhere, and communities from the five clusters cover a wide range of geographical and environmental conditions. Agricultural practices significantly decrease abundance, although the presence of tree components alleviates this effect