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PurposeTo assess the benefit-to-risk balance of bronchoalveolar lavage (BAL) in intensive care unit (ICU) patients.MethodsIn 16 ICUs, we prospectively collected adverse events during or within 24 h after BAL and assessed the BAL input for decision making in consecutive adult patients. The occurrence of a clinical adverse event at least of grade 3, i.e., sufficiently severe to need therapeutic action(s), including modification(s) in respiratory support, defined poor BAL tolerance. The BAL input for decision making was declared satisfactory if it allowed to interrupt or initiate one or several treatments.ResultsWe included 483 BAL in 483 patients [age 63 years (interquartile range (IQR) 53–72); female gender: 162 (33.5%); simplified acute physiology score II: 48 (IQR 37-61); immunosuppression 244 (50.5%)]. BAL was begun in non-intubated patients in 105 (21.7%) cases. Sixty-seven (13.9%) patients reached the grade 3 of adverse event or higher. Logistic regression showed that a BAL performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 BAL performed) was the main predictor of poor BAL tolerance in non-intubated patients [OR: 3.57 (95% confidence interval 1.04–12.35); P = 0.04]. A satisfactory BAL input for decision making was observed in 227 (47.0%) cases and was not predictable using logistic regression.ConclusionsAdverse events related to BAL in ICU patients are not infrequent nor necessarily benign. Our findings call for an extreme caution, when envisaging a BAL in ICU patients and for a mandatory accompaniment of the less experienced physicians.

IntroductionCorticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids.Methods and analysisRECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%–10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids’ effect in each subset, and (2) measure of interaction.Ethics and disseminationThe protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov Registry (NCT04280497).

Although many risk models have been tested in patients implanted by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), few scores assessed patients’ prognosis in the setting of ST-segment elevation myocardial infarction (STEMI) with refractory cardiogenic shock. We aimed at assessing the performance of risk scores, notably the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score, for predicting mortality in this particular population. This retrospective observational study included patients admitted to Tours University Hospital for STEMI with cardiogenic shock and requiring hemodynamic support by VA-ECMO. Among the fifty-one patients, the 30-day and 6-month survival rates were 63% and 56% respectively. Thirty days after VA-ECMO therapy, probabilities of mortality were 12, 17, 33, 66, 80% according to the ENCOURAGE score classes 0–12, 13–18, 19–22, 23–27, and ≥28, respectively. The ENCOURAGE score (AUC of the Receiving Operating Characteristic curve = 0.83) was significantly better compared to other risk scores. The hazard ratio for survival at 30 days for each point of the ENCOURAGE score was 1.10 (CI 95% (1.06, 1.15); p < 0.001). Decision curve analysis indicated that the ENCOURAGE score had the best clinical usefulness of the tested risk scores and the Hosmer–Lemeshow test suggested an accurate calibration. Our data suggest that the ENCOURAGE score is valid and the most relevant score to predict 30-day mortality after VA-ECMO therapy in STEMI patients with refractory cardiogenic shock. It may help decision-making teams to better select STEMI patients with shock for VA-ECMO therapy.

Vitis vinifera commonly known as grapevine is one of the most important fruit crops worldwide. Its cultivation started more than 7000 years ago in the Near East, and over the millennia was followed by the development of thousands of cultivars that were further selected and characterized for specific purposes. Its important pharmacological value and its richness in phytoconstituents were the triggers to perform this project. Seven extracts were prepared from five different V. vinifera varieties (V. vinifera ‘Black Pearl’ (BP), V. vinifera ‘Red Glob’ (RG), V. vinifera ‘Crimson’ (CR), V. vinifera ‘Beitamouni’ (BE) and V. vinifera ‘Superior’ (SU)) by separating the pulp from the seeds, followed by methanolic extraction. The phytochemical analysis showed that red colored grapes (RE, BP and CR), the seeds from V. vinifera ‘Black Pearl’ and V. vinifera ‘Red Globe’ contain higher amounts of primary and secondary metabolites such as polyphenols, anthocyanins and reducing sugars. In addition to their richness in phytoconstituents, these varieties/seeds possess an important antioxidant activity. The results of the cell viability assays showed that the red varieties have a potential anticancer activity against Capan-2 pancreatic cancer and MDA-MB231(TNBC) breast cancer cell lines, with the greatest promise when combined with the seeds.

Cancer is a major public health problem that ranks as the second leading cause of death. Anti-cancer drug development presents with various hurdles faced throughout the process. Nanoparticle (NP) formulations have emerged as a promising strategy for enhancing drug delivery efficiency, improving stability, and reducing drug toxicity. Previous studies have shown that the adamantyl retinoid ST1926 displays potent anti-tumor activities in several types of tumors, particularly in colorectal cancer (CRC). However, phase I clinical trials in cancer patients using ST1926 are halted due to its low bioavailability. In this manuscript, we developed ST1926-NPs using flash nanoprecipitation with polystyrene-b-poly (ethyleneoxide) as an amphiphilic stabilizer and cholesterol as a co-stabilizer. Dynamic light scattering revealed that the resulting ST1926-NPs Contin diameter was 97 nm, with a polydispersity index of 0.206. Using cell viability, cell cycle analysis, and cell death assays, we showed that ST1926-NP exhibited potent anti-tumor activities in human CRC HCT116 cells. In a CRC xenograft model, mice treated with ST1926-NP exhibited significantly lowered tumor volumes compared to controls at low drug concentrations and enhanced the delivery of ST1926 to the tumors. These findings highlight the potential of ST1926-NPs in attenuating CRC tumor growth, facilitating its further development in clinical settings.

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide-A (Sal-A) and salograviolide-B (Sal-B) are two STLs that have been isolated from Centaurea ainetensis, an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal-A and Sal-B were modified and successfully prepared into eight novel guaianolide-type STLs (compounds 1–8) bearing ester groups of different geometries. Sal-A, Sal-B, and compounds 1–8 were tested against a human colorectal cancer cell line model with differing p53 status; HCT116 with wild-type p53 and HCT116 p53−/− null for p53, and the normal-like human colon mucosa cells with wild-type p53, NCM460. IC50 values indicated that derivatization of Sal-A and Sal-B resulted in potentiation of HCT116 cell growth inhibition by 97% and 66%, respectively. The effects of the different molecules on cancer cell growth were independent of p53 status. Interestingly, the derivatization of Sal-A and Sal-B molecules enhanced their anti-growth properties versus 5-Fluorouracil (5-FU), which is the drug of choice in colorectal cancer. Structure-activity analysis revealed that the enhanced molecule potencies were mainly attributed to the position and number of the hydroxy groups, the lipophilicity, and the superiority of ester groups over hydroxy substituents in terms of their branching and chain lengths. The favorable cytotoxicity and selectivity of the potent molecules, to cancer cells versus their normal counterparts, pointed them out as promising leads for anti-cancer drug design.

Table grapes are harvested based on well-known maturity indices that must be monitored after fruit veraison. The aim of this study was to assess these indices across multiple locations and environmental conditions, encompassing different table grape cultivars such as Black Pearl, Crimson Seedless, Superior Seedless, and Red Globe. For this reason, grape sampling was conducted across six distinct locations characterized by varying altitudes above sea level (m asl) and environmental conditions over the ripening season. The main maturity indices, including pH, sugar content, titratable acidity, berry firmness, and other parameters were monitored over the growing season. Moreover, the quantification of total polyphenols, total anthocyanins, and antioxidant activity was determined using spectrophotometric assays at harvesting. The study has examined the effect of the vineyard’s location on grape quality and its interaction with the cultivar and environment. Crimson Seedless maintained a relatively high level of acidity with altitude near harvesting. Black Pearl exhibited a notable decline in both sugar content and berry firmness as elevation increased, whereas Red Globe demonstrated contrasting outcomes. The optimal maturity of Superior Seedless was observed at an elevation of 1000 m asl. Black Pearl and Crimson Seedless exhibited better adaptability to intermediate elevations (650 and 950 m asl), while Red Globe and Superior Seedless showed better adaptability to higher elevations (1000–1150 m asl). Among the studied cultivars, Black Pearl exhibited significantly higher levels of total polyphenols and anthocyanins, while close values were noticed between red and green cultivars.

Vitis vinifera commonly known as grapevine is one of the most important fruit crops worldwide. Its cultivation started more than 7000 years ago in the Near East, and over the millennia was followed by the development of thousands of cultivars that were further selected and characterized for specific purposes. Its important pharmacological value and its richness in phytoconstituents were the triggers to perform this project. Seven extracts were prepared from five different V. vinifera varieties (V. vinifera ‘Black Pearl’ (BP), V. vinifera ‘Red Glob’ (RG), V. vinifera ‘Crimson’ (CR), V. vinifera ‘Beitamouni’ (BE) and V. vinifera ‘Superior’ (SU)) by separating the pulp from the seeds, followed by methanolic extraction. The phytochemical analysis showed that red colored grapes (RE, BP and CR), the seeds from V. vinifera ‘Black Pearl’ and V. vinifera ‘Red Globe’ contain higher amounts of primary and secondary metabolites such as polyphenols, anthocyanins and reducing sugars. In addition to their richness in phytoconstituents, these varieties/seeds possess an important antioxidant activity. The results of the cell viability assays showed that the red varieties have a potential anticancer activity against Capan-2 pancreatic cancer and MDA-MB231(TNBC) breast cancer cell lines, with the greatest promise when combined with the seeds.

Background: Leafy greens, particularly romaine lettuce, are often associated with outbreaks due to their susceptibility to contamination from various environmental sources. This study aimed to evaluate the presence of E. coli, Salmonella, copper, nickel, zinc, and manganese in irrigation water, lettuce leaves, and agricultural soil in the Litani River Basin (LRB), Lebanon. Method: Samples were collected from five demonstration plots employing different agricultural practices. Heavy metal concentrations were determined using atomic absorption spectrometry, while E. coli and Salmonella testing were conducted through conventional culturing techniques. The impact of E. coli contamination on seed germination and the interaction effects between E. coli and heavy metals were also examined. The study also compared the effectiveness of various irrigation systems in reducing bacterial contamination. Results: The results demonstrated that contamination levels varied significantly across the plots and irrigation types. This variation underscores the necessity of site-specific mitigation strategies to enhance food safety. Our findings highlight the importance of selecting appropriate irrigation methods and implementing tailored agricultural practices to minimize the risk of contamination. Conclusion: This research provides valuable insights for optimizing agricultural practices in the LRB to ensure food safety and environmental sustainability.