ECMO Alone Versus ECPELLA in Patients Affected by Cardiogenic Shock: The Multicenter EVACS Study.

The objective was to investigate the outcomes of concomitant venoarterial extracorporeal membrane oxygenation (ECMO) and left ventricular unloading with Impella (ECPELLA) compared with ECMO alone to treat patients affected by cardiogenic shock. Data from patients needing mechanical circulatory support from 4 international centers were analyzed. Of 438 patients included, ECMO alone and ECPELLA were adopted in 319 (72.8%) and 119 (27.2%) patients, respectively. Propensity score matching analysis identified 95 pairs. In the matched cohort, 30-day mortality rates in the ECMO and ECPELLA were 49.5% and 43.2% ( P = 0.467). The incidences of complications did not differ significantly between groups ( P = 0.877, P = 0.629, P = 1.000, respectively). After a median follow-up of 0.18 years (interquartile range 0.02-2.55), the use of ECPELLA was associated with similar mortality compared with ECMO alone (hazard ratio 0.81, 95% confidence interval 0.54-1.20, P = 0.285), with 1-year overall survival rates of 51.3% and 46.6%, for ECPELLA and ECMO alone, respectively. ECMO alone and ECPELLA are both effective strategies in patients needing mechanical circulatory support for cardiogenic shock, showing similar rates of early and mid-term survival.

Trifluridine/tipiracil + oxaliplatin ± nivolumab vs FOLFOX ± nivolumab in HER2 negative advanced oesogastric adenocarcinoma: The PRODIGE73-UCGI40-LOGICAN trial.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. AIMS: The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. METHODS: This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. DISCUSSION: PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).

Lead removal from the aqueous solution by extracellular polymeric substances produced by the marine diatom Navicula salinicola.

Microbial extracellular polymeric substances (EPS) have recently emerged as significant contributors in diverse biotechnological applications. Extracellular polymeric substances (EPS), produced by a Navicula salinicola strain, have been studied for potential applications in a specific heavy metal (lead (Pb II)) removal from wastewater. The optimisation of operational parameters, mainly pH, Pb and EPS concentrations, using the Box-Behnken design (BBD) was undertaken to enhance lead uptake. The higher Pb adsorption capacity reached 2211.029 mg/g. Hydroxyl, carbonyl, carboxyl, phosphoric, and sulfhydryl groups were identified quantitatively as potential sites for Pb adsorption. EPS exhibited a notable flocculation rate of 70.20% in kaolin clay at a concentration of 15 mg/L. They demonstrated an emulsifying activity greater than 88%, showcasing their versatile potential for both sedimentation processes and stabilising liquid-liquid systems. EPS could be excellent nonconventional renewable biopolymers for treating water and wastewater.

A sulfated exopolysaccharide derived from Chlorella sp. exhibiting in vitro anti-α-D-Glucosidase activity.

There is a great scientific curiosity to discover all environments sheltering microalgae, especially those with exceptional characteristics from coldest to hottest ones, the purpose remains to explore the potential of the native microalgae flora and the research for new bioactive compounds. This study aimed to isolate a polysaccharide-producing microalga from an extreme ecosystem and to evaluate its capacity to inhibit the α-D-glucosidase enzyme. Chlorella strain is isolated from hypersaline Lake in the Algerian desert. The exopolysaccharide extraction was performed by the concentration of free-cell supernatant in a rotary evaporator. The infrared analysis showed a characteristic footprint of carbohydrates with particular functional groups, such as sulfate. Gas chromatography-mass spectrometry has revealed a hetero-exopolysaccharide composed of galactose 35.75%, glucose 21.13%, xylose 16.81%, fructose 6.96%, arabinose 5.10%, and glucuronic acid 2.68%. The evaluation of the anti-hyperglycemic activity demonstrated a significant α-D-glucosidase inhibition of 80.94 ± 0.01% at 10 mg mL-1 with IC50 equal to 4.31 ± 0.20 mg mL-1. This study opens a vast prospect to use exopolysaccharides as natural nutraceutical or food additive.

Standardized Bench Test Evaluation of Biomechanical Characteristics of Stents Used in Right Ventricular Outflow Tract Revalvulation.

PURPOSE: Pre-stenting of the right ventricular outflow tract (RVOT) is commonly performed before percutaneous pulmonary valve implantation (PPVI), to relieve obstruction, prevent valved stent fractures, and provide a landing zone. This study aimed to evaluate the biomechanical characteristics of the stents currently used to perform pre-stenting of the RVOT. METHODS: We assessed five commercially available stents: Cheatham-Platinum Stent ("CP Stent"), AndraStent XL, AndraStent XXL, Optimus XL, and Optimus XXL. Following stent deployment at nominal pressure, radial and longitudinal elastic recoils and radial resistance were measured. The bending stiffness of the stents crimped onto the balloons was also evaluated. RESULTS: Three samples were tested for each stent. Our study showed no significant difference between the stent platforms in terms of radial elastic recoil, which was relatively low (< 10%). The longitudinal elastic recoil was also low for all the devices (< 5%). Significant differences were observed in radial resistance (P < 0.001). CP Stent and AndraStent XL exhibited the highest radial resistances. The bending stiffnesses of the stents crimped on their balloons were significantly different (P < 0.00001). Optimus XL and XXL were more flexible than the other stents. CONCLUSION: This study highlights the significant differences between the stents currently used in RVOT pre-stenting. Stents with good radial resistance are preferred, especially for calcified vessels, and flexibility is crucial for tortuous vessels. We proposed an algorithm for selecting the most suitable stent according to the need for radial force and flexibility, which will help inform clinicians considering RVOT revalvulation.

Exopolysaccharide from marine microalgae belonging to the Glossomastix genus: fragile gel behavior and suspension stability.

With the aim to find new polysaccharides of rheological interest with innovated properties, rhamnofucans produced as exopolysaccharides (EPS) in a photobioreactor (PBR) and an airlift bioreactor (ABR) by the marine microalgae Glossomastix sp. RCC3707 and RCC3688 were fully studied. Chemical characterizations have been conducted (UHPLC - MS HR). Analyses by size-exclusion chromatography (SEC) coupled online with a multiangle light scattering detector (MALS) and a differential refractive index detector showed the presence of large structures with molar masses higher than 106 g.mol-1. The rheological studies of these EPS solutions, conducted at different concentrations and salinities, have evidenced interesting and rare behavior characteristic of weak and fragile hydrogels i.e. gel behavior with very low elastic moduli (between 10-2 and 10 Pa) and yield stresses (between 10-2 and 2 Pa) according to the EPS source, concentration, and salinity. These results were confirmed by diffusing wave spectroscopy. Finally, as one of potential application, solutions of EPS from Glossomastix sp. have evidenced very good properties as anti-settling stabilizers, using microcrystalline cellulose particles as model, studied by multiple light scattering (MLS) with utilization in cosmetic or food industry. Compared to alginate solution with same viscosity for which sedimentation is observed over few hours, microalgae EPS leads to a stable suspension over few days.

Galectin-1 Modulates the Fusogenic Activity of Placental Endogenous Retroviral Envelopes.

Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other cell fusion events. Since galectin-1 is a ß-galactoside-binding protein associated with cytotrophoblast fusion during placental development, we previously tested its effect on Syncytin-mediated cell fusion and showed that this protein differently modulates the fusogenic potential of Syncytin-1 and -2. Herein, we were interested in comparing the impact of galectin-1 on hERV envelope proteins in different cellular contexts. Using a syncytium assay, we first demonstrated that galectin-1 increased the fusion of Syncytin-2- and EnvP(b)-expressing cells. We then tested the infectivity of Syncytin-1 and -2 vs. VSV-G-pseudotyped viruses toward Cos-7 and various human cell lines. In the presence of galectin-1, infection of Syncytin-2-pseudotyped viruses augmented for all cell lines. In contrast, the impact of galectin-1 on the infectivity of Syncytin-1-pseudotyped viruses varied, being cell- and dose-dependent. In this study, we report the functional associations between three hERV envelope proteins and galectin-1, which should provide information on the fusogenic activity of these proteins in the placenta and other biological and pathological processes.

Impella for the Management of Ventricular Septal Defect Complicating Acute Myocardial Infarction: A European Multicenter Registry.

Ventricular septal defect (VSD) is a rare but severe complication of myocardial infarction (MI). Temporary mechanical circulatory support (MCS) can be used as a bridge to VSD closure, heart transplantation, or ventricular assist device. We describe the use of Impella device in this context based on a multicenter European retrospective registry (17 centers responded). Twenty-eight post-MI VSD patients were included (Impella device were 2.5 for 1 patient, CP for 20, 5.0 for 5, and unknown for 2). All patients were in cardiogenic shock with multiple organ failure (SAPS II 41 [interquantile range {IQR} = 27-53], lactate 4.0 ± 3.5 mmol/L) and catecholamine support (dobutamine 55% and norepinephrine 96%). Additional temporary MCS was used in 14 patients (50%), mainly extracorporeal life support (ECLS) (n = 9, 32%). Severe bleedings were frequent (50%). In-hospital and 1 year mortalities were 75%. Ventricular septal defect management was surgical for 36% of patients, percutaneous for 21%, and conservative for 43%. Only surgically managed patients survived (70% in-hospital survival). Type and combination of temporary MCS used were not associated with mortality (Impella alone or in combination with intra-aortic balloon pump [IABP] or ECLS, p = 0.84). Impella use in patients with post-MI VSD is feasible but larger prospective registries are necessary to further elucidate potential benefits of left ventricular unloading in this setting.

Role of some structural features in EPS from microalgae stimulating collagen production by human dermal fibroblasts.

Exopolysaccharides (EPS) from the microalgae Porphyridium cruentum, Chrysotila dentata, Pavlova sp., Diacronema sp., Glossomastix sp., Phaeodactylum tricornutum, and Synechococcus sp. were isolated and depolymerized. First, EPS were submitted to a high pressure pre-treatment step, followed by a solid acid-catalyzed hydrolysis step carried out in a batch or recycle fixed-bed reactor, using a strong acidic cation-exchange resin. Twenty-eight different EPS forms were thus obtained. After characterization of their main structural features (weight- and number-averaged molecular weight, polydispersity index, sulfate and uronic acid contents), we investigated the structure-function relationship of their pro-collagen activity. We found that native microalgae EPS were able to inhibit until 27% of human matrix metalloproteinase-1 (MMP-1) activity while the depolymerized forms were able to enhance collagen production by two different human fibroblast lines, used as cell models due to their major role in dermal collagen biosynthesis. The most active EPS forms, obtained by depolymerization in the recycle fixed-bed reactor of D. ennorea and Glossomastix sp. EPS, led to 390% increase in collagen production. Finally, principal component (PCA) and Pearson analyses indicated that MMP-1 inhibition was strongly correlated to the sulfate group content of EPS whereas collagen production by fibroblasts was mostly related to their proportion of low molecular weight polysaccharides (<10 kDa). Uronic acid content of EPS was also shown essential but only if the size of EPS was reduced in the first place. Altogether, these results gave new insights of the dermo-cosmetic potential of microalgae EPS as well as the key parameters of their activity.

Six new and original EPS from microalgae were isolated.Microalgae EPS were depolymerized by high pressure/solid acid-catalyzed hydrolysis.Native EPS inhibited human matrix metalloproteinase-1.Depolymerized EPS highly stimulated collagen production by human dermal fibroblasts.Structure­function studies revealed that sulfate groups and MW of EPS were crucial.

Primary structural features, physicochemical and biological properties of two water-soluble polysaccharides extracted from the brown Tunisian seaweed Halopteris scoparia.

Marine algae are the most abundant resource in the marine environment and are still a promising source of bioactive compounds including hydrocolloids. This study contributes to the evaluation of the biological and biotechnological potentials of two water soluble polysaccharides, namely alginates (AHS) and fucoidan (FHS), extracted and purified from Halopteris scoparia, an abundant Tunisian brown macroalgae collected in Tunisia (Tabarka region). The total sugars, neutral monosaccharides, uronic acids, proteins, polyphenols, and sulfate groups contents were quantified for both fractions, as well as their functional groups and primary structural features by Fourier transform infrared spectroscopy, ionic and/or gas chromatography and nuclear magnetic resonance analyses. AHS and FHS showed significant anti-inflammatory (IC50 ≈ 1 mg/mL), anticoagulant (e.g., 27-61.7 for the activated partial thromboplastin time), antihyperglycemic (0.1-40 µg/mL) and anti-trypsin (IC50 ≈ 0.3-0.4 mg/mL) effects. FHS and a hydrolyzed fraction showed a very promising potential against herpes viruses (HSV-1) (IC50 < 28 µg/mL). Besides, AHS and two hydrolyzed fractions were able to stimulate the natural defenses of tomato seedlings, assessing their elicitor capacity, by increasing the activity of phenylalanine ammonia-lyase (66-422 %) but also significantly changing the polyphenol content in the leaves (121-243 %) and roots (30-104 %) of tomato plants.

Bioprospecting for industrially relevant exopolysaccharide-producing cyanobacteria under Portuguese simulated climate.

Cyanobacterial exopolysaccharides (EPS) are potential candidates for the production of sustainable biopolymers. Although the bioactive and physicochemical properties of cyanobacterial-based EPS are attractive, their commercial exploitation is limited by the high production costs. Bioprospecting and characterizing novel EPS-producing strains for industrially relevant conditions is key to facilitate their implementation in various biotechnological applications and fields. In the present work, we selected twenty-five Portuguese cyanobacterial strains from a diverse taxonomic range (including some genera studied for the first time) to be grown in diel light and temperature, simulating the Portuguese climate conditions, and evaluated their growth performance and proximal composition of macronutrients. Synechocystis and Cyanobium genera, from marine and freshwater origin, were highlighted as fast-growing (0.1-0.2 g L-1 day-1) with distinct biomass composition. Synechocystis sp. LEGE 07367 and Chroococcales cyanobacterium LEGE 19970, showed a production of 0.3 and 0.4 g L-1 of released polysaccharides (RPS). These were found to be glucan-based polymers with high molecular weight and a low number of monosaccharides than usually reported for cyanobacterial EPS. In addition, the absence of known cyanotoxins in these two RPS producers was also confirmed. This work provides the initial steps for the development of cyanobacterial EPS bioprocesses under the Portuguese climate.

Optimization of energy recovery efficiency from sweet sorghum stems by ethanol and methane fermentation processes coupling.

Taken separately, a single sweet sorghum stem bioconversion process for bioethanol and biomethane production only leads to a partial conversion of organic matter. The direct fermentation of crushed whole stem coupled with the methanization of the subsequent solid residues in a two-stage process was experimented to improve energy bioconversion yield, efficiency, and profitability. The raw stalk calorific value was 17,144.17 kJ/kg DM. Fermentation step performed using Saccharomyces cerevisiae resulted in a bioconversion yield of 261.18 g Eth/kg DM, i.e. an energy recovery efficiency of 6921.27 kJ/kg DM. The methanogenic potentials were 279 and 256 LCH4/kg DM, respectively, for raw stem and fermentation residues, i.e. energy yields of 10,013.31 and 9187.84 kJ/kg DM, respectively. Coupling processes have significantly increased yield and made it possible to reach 13,309.57 kJ/kg DM, i.e. 77.63% of raw stem energy recovery yield, compared to 40.37% and 58.40%, respectively, for single fermentation and methanization processes.

Sweet sorghum stem is a viable feedstock source for efficient coproduction of ethanol and methaneSorghum stems calorific value determination revealed an energy potential of 17.15 MJ/kg DMEnergy recovery by single methanization yielded 18.03% more than ethanol fermentationCoupling processes has significantly increased energy recovery yield and profitability.

The ideal vulnerable road user - a study of parameters affecting VRU detection.

OBJECTIVE: Advanced Driving Assistance Systems (ADAS) have the potential to reduce occurrences and severity of collisions with Vulnerable Road Users (VRUs). However, the nearly infinite number of possible VRU visual appearances (e.g., size, clothing, accessories) represent a technical challenge as systems need to correctly detect and identify VRUs to take adequate mitigation measures. The aim of this study was to determine, through track testing, which parameters affect systems' capabilities in detecting pedestrians. METHODS: The standardized articulated adult male pedestrian (EPTa) and seven-year-old articulated child pedestrian (EPTc) targets were used as the control group. Evaluations on the track followed the Euro NCAP AEB-VRU test protocols, and derivatives thereof. An iterative test approach was used to benchmark the detection capabilities of systems with variations in target configuration and environmental conditions against the control group (baseline condition). Over 1,000 track tests using 24 configurations and 13 vehicles (model years 2019-2021) were conducted. The environmental conditions included nighttime and snow-covered roads. Pedestrians were dressed in winter clothing and/or equipped with accessories, including a hat, jackets of different colors, backpack, umbrella, and a scooter. Other scenarios involved parked vehicles as obstructions or using multiple pedestrian targets (to simulate a parent crossing the road with child or a crowd waiting at an intersection) to challenge the vehicles with realistic urban-like scenarios. RESULTS: This study illustrates how the variation of parameters outside the baseline condition can affect a vehicles' safety performance. Weather conditions and urban-like scenarios on the test track affected some systems more than others. The validity of these findings is however limited by the small vehicle sample size and number of tests performed per scenario. CONCLUSIONS: In Canada, vehicles are exposed to less-than-ideal road conditions and a wide range of pedestrian profiles. The vehicles tested demonstrated various levels of performance and capabilities when mitigating collisions with pedestrians. The research illustrates the safety risks associated with weather and types of VRUs.

Elicitor Activity of Low-Molecular-Weight Alginates Obtained by Oxidative Degradation of Alginates Extracted from Sargassum muticum and Cystoseira myriophylloides.

Alginates extracted from two Moroccan brown seaweeds and their derivatives were investigated for their ability to induce phenolic metabolism in the roots and leaves of tomato seedlings. Sodium alginates (ALSM and ALCM) were extracted from the brown seaweeds Sargassum muticum and Cystoseira myriophylloides, respectively. Low-molecular-weight alginates (OASM and OACM) were obtained after radical hydrolysis of the native alginates. Elicitation was carried out by foliar spraying 20 mL of aqueous solutions (1 g/L) on 45-day-old tomato seedlings. Elicitor capacities were evaluated by monitoring phenylalanine ammonia-lyase (PAL) activity, polyphenols, and lignin production in the roots and leaves after 0, 12, 24, 48, and 72 h of treatment. The molecular weights (Mw) of the different fractions were 202 kDa for ALSM, 76 kDa for ALCM, 19 kDa for OACM, and 3 kDa for OASM. FTIR analysis revealed that the structures of OACM and OASM did not change after oxidative degradation of the native alginates. These molecules showed their differential capacity to induce natural defenses in tomato seedlings by increasing PAL activity and through the accumulation of polyphenol and lignin content in the leaves and roots. The oxidative alginates (OASM and OACM) exhibited an effective induction of the key enzyme of phenolic metabolism (PAL) compared to the alginate polymers (ALSM and ALCM). These results suggest that low-molecular-weight alginates may be good candidates for stimulating the natural defenses of plants.

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.

BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

Description of the Wild Strain Rhizobium rosettiformans DSM26376, Reclassified under Peteryoungia rosettiformans comb.nov., for Producing Glucuronan.

Glucuronan is a polysaccharide composed of ß-(1,4)-linked d-glucuronic acids having intrinsic properties and biological activities recoverable in many fields of application. Currently, the description of Sinorhyzobium meliloti M5N1CS mutant bacterial strain as the sole source of glucuronan makes it relevant to the exploration of new microorganisms producing glucuronan. In this study, the Peteryoungia rosettifformans strain (Rhizobia), was identified as a wild producer of an exopolysaccharide (RhrBR46) related to glucuronan. Structural and biochemical features, using colorimetric assays, Fourier infrared spectroscopy, nuclear magnetic resonance, high pressure size exclusion chromatography coupled to multi-angle light laser scattering, and enzymatic assays allowed the characterization of a polyglucuronic acid, having a molecular mass (Mw¯) of 1.85 × 105 Da, and being partially O-acetylated at C-2 and/or C-3 positions. The concentration of Mg2+ ions in the cultivation medium has been shown to impact the structure of RhrBR46, by reducing drastically its Mw¯ (73%) and increasing its DA (10%). Comparative structural analyses between RhrBR46 and the glucuronan from Sinorhyzobium meliloti M5N1CS strain revealed differences in terms of molecular weight, degree of acetylation (DA), and the distribution of acetylation pattern. These structural divergences of RhrBR46 might contribute to singular properties or biological activities of RhrBR46, offering new perspectives of application.