Relationship between positive end-expiratory pressure levels, central venous pressure, systemic inflammation and acute renal failure in critically ill ventilated COVID-19 patients: a monocenter retrospective study in France

Background The role of positive pressure ventilation, central venous pressure (CVP) and inflammation on the occurrence of acute kidney injury (AKI) have been poorly described in mechanically ventilated patient secondary to coronavirus disease 2019 (COVID-19). Methods This was a monocenter retrospective cohort study of consecutive ventilated COVID-19 patients admitted in a French surgical intensive care unit between March 2020 and July 2020. Worsening renal function (WRF) was defined as development of a new AKI or a persistent AKI during the 5 days after mechanical ventilation initiation. We studied the association between WRF and ventilatory parameters including positive end-expiratory pressure (PEEP), CVP, and leukocytes count. Results Fifty-seven patients were included, 12 (21%) presented WRF. Daily PEEP, 5 days mean PEEP and daily CVP values were not associated with occurrence of WRF. 5 days mean CVP was higher in the WRF group compared to patients without WRF (median [IQR], 12 mm Hg [11-13] vs. 10 mm Hg [9–12]; P=0.03). Multivariate models with adjustment on leukocytes and Simplified Acute Physiology Score (SAPS) II confirmed the association between CVP value and risk of WRF (odd ratio, 1.97; 95% confidence interval, 1.12–4.33). Leukocytes count was also associated with occurrence of WRF in the WRF group (14 G/L [11–18]) and the no-WRF group (9 G/L [8–11]) (P=0.002). Conclusions In mechanically ventilated COVID-19 patients, PEEP levels did not appear to influence occurrence of WRF. High CVP levels and leukocytes count are associated with risk of WRF

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Molecular tools for metalloprotease sub-proteome generation

Collet M, Lenger J, Jenssen K, Plattner HP, Sewald N. Molecular tools for metalloprotease sub-proteome generation. Journal of Biotechnology. 2007;129(2):316-328.Molecular systems biology, the highly challenging post-genomic research area has many different facets like transcriptomics, proteomics, metabolomics, interactomics, modelling of cell cycles, etc. Among them, functional proteomics and interactomics represent exciting fields of research with high relevance towards biochemistry, medicinal chemistry, therapy, biotechnology and bioinformatics. The number of different proteins expressed by a cell under a set of certain conditions and the high dynamic range of these proteins together with different activation states require methods for sub-proteome generation on a mechanistic basis to reduce the amount of data. This can be achieved by application of tailor-made molecular tools that are based on inhibitors or, more generally, on protein ligands. Immobilised protein ligands proved to be suitable for the generation of sub-proteomes by affinity chromatography or by fishing using magnetic beads. Metalloproteases share a catalytically active metal ion in the active site. They can for example be addressed by hydroxamate type inhibitors like marimastat which are suitable for targeting active metalloproteases on a mechanistic basis aiming at the generation of an activity- and affinity-based sub-proteome. For such purposes, modified hydroxamate type inhibitors can be attached to a solid surface, e.g., chromatography material, magnetic beads, or a surface plasmon resonance sensor chip. The latter technique is a valuable tool for the optimisation of binding and elution conditions of biomolecules in affinity chromatography or on experiments using magnetic beads. Preliminary results are reported on the application of these probes in fishing experiments using magnetic beads. (c) 2007 Elsevier B.V. All rights reserved

Surg Endosc

Laparoscopic adrenalectomy (LA) is the gold standard for the resection of most adrenal lesions. A precise delineation of factors influencing its outcomes is lacking. The aim of this study was to assess factors associated with intraoperative complications, postoperative complications, and prolonged length of stay (LOS) after LA. Patients who underwent LA from 1999 to 2021 in a single-academic-institution were included. Patient and disease-specific data, intraoperative complications, postoperative complications according to Dindo-Clavien (DC) scale, and LOS were recorded. Predictive factors of complications and prolonged LOS were determined by logistic regression. We identified 530 patients who underwent 547 LA. Intraoperative complications occurred in 33 patients (6.0%). Postoperative complications ≥  DC grade 2 occurred in 73 patients (13.35%); severe postoperative complications ≥ DC grade 3 in 14 patients (2.56%). Postoperative complications were positively associated with age ≥ 72 (OR 1.14 [95% CI 1.02-1.29]), intraoperative complications (OR 1.36 [95% CI 1.14-1.63]), and negatively associated with non functional adenomas (OR 0.88 [95% CI 0.7-0.99]), and right adrenalectomy (OR 0.91 [95% CI 0.86-0.97]). Severe postoperative complications were positively associated with chronic obstructive pulmonary disease (COPD, OR 1.08 [95% CI 1.00-1.17]), and negatively associated with right adrenalectomy (OR 0.97 [95% CI 0.92-0.99]). Prolonged LOS was associated with age ≥ 72 (OR 1.21 [95% CI 1.05-1.41]), and COPD (OR 1.20 [95% CI 1.01-1.44]). LA remains safe when performed by surgeons with expertise. Right adrenalectomy resulted in less postoperative overall and severe complications. The risk-benefit equation should be carefully assessed before left LA in older patients with COPD

Preparation and characterization of a biologic scaffold for esophageal tissue engineering

The aim of this work is to obtain a suitable matrix for tissue engineering of the esophagus. Swine esophagi are decellularized following a new dynamic process. In vitro biocompatibility is evaluated and histological analyses and circumferential and longitudinal traction tests are performed. The results are encouraging, showing good decellularization and maintaining tissue structure, no toxicity of the final tubular matrix and mechanical properties compatible with the specifications of an esophagus substitute

Physico-chemical and agronomic results of soil remediation by In Situ Chemical Reduction applied to a chlordecone-contaminated nitisol at plot scale in a French Caribbean banana plantation

International audienceThe In Situ Chemical Reduction (ISCR) process was tested in a nitisol in a French Caribbean banana plantation using five different soil amendments. The addition of 2.8% or 4.0% of Zero Valent Iron (ZVI; dw/dw, 2 different trial plots) in the 0–40-cm soil layer lowered the initial chlordecone (CLD) concentration by up to 74% or 69% in 37 days or 94 days, with 75% of the decrease achieved after only 21 or 24 days of treatment depending on the trial plot. The addition of commercially available Daramend® was also tested by applying the 6% dose (dw/dw) recommended by the manufacturer and using either the regular alfalfa-based product or a bagasse-based product specifically formulated for the study. Both significantly lowered CLD concentrations, but to a lesser extent than with the ZVI-only amendment. A bagasse-ZVI mixture prepared on site produced results slightly better than the two Daramend®. The percentage decreases in CLD concentrations were correlated with the negative redox potentials achieved. In all the trial plots, dechlorinated transformation products appeared in the soil and soil water as the CLD concentrations decreased, with H atoms replacing up to 4 and 7 of the 10 Cl atoms, respectively. None of these degradation products appeared to accumulate in the soil or soil water during the treatment. Instead, the reverse occurred, with an overall downward trend in their concentrations over time. The effects of ISCR treatment on agronomic and human health–related parameters were measured in three different crops. The radishes produced with some treatments were visually of lower quality or smaller in size than those grown in the control plots. Lower yields were observed for the cucumbers and sweet potatoes grown after applying the bagasse-based amendments. Mortality among cucumber seedlings was observed after treatment with ZVI only. Simple operational solutions should suffice to remedy these negative agronomic effects. As regards human health–related effects, the CLD concentrations in radishes grown with three of the amendments were significantly lower than in the two control plots and well below the maximum residue level (MRL), which was substantially exceeded in the radishes grown on untreated soil. For cucumbers, the treatments with regular Daramend® and with a local bagasse-ZVI mixture produced fruits with CLD below the MRL and also below the concentrations in one of the two control plots. As for the sweet potatoes, adding a bagasse-ZVI mixture had a significant positive effect by decreasing contamination below the levels in the two control plots and below the MRL

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

International audienceDiagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients (n = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (Af-qPCR), and galactomannan testing were performed on all respiratory samples (n = 350). Serum galactomannan, β-d-glucan, and plasma Af-qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test, P = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) (P < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

International audienceDiagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients (n = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (Af-qPCR), and galactomannan testing were performed on all respiratory samples (n = 350). Serum galactomannan, β-d-glucan, and plasma Af-qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test, P = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) (P < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately