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Abstract Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets ( 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of tartrazine as sensory additive (functional group: (a) colourants: (i) substances that add or restore colour in feedingstuffs). Tartrazine is intended to be incorporated in fishing baits up to a maximum of 30 mg/kg in complementary feed in order to colour them and attract fish in freshwater (ponds, rivers), for both recreational and competitive fishing. The additive is not intended for use in aquaculture. Tartrazine is already authorised for use with cats and dogs, ornamental fish, grain‐eating ornamental birds and small rodents. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of tartrazine in the preparation of baits for freshwater fish under the proposed conditions of use is of no concern for the target animals. The use of tartrazine as a feed additive under the proposed conditions of use is considered safe for the consumer and the environment. Regarding the user safety, the additive should be considered a dermal and respiratory sensitiser. Inhalation and dermal exposure are considered a risk. The FEEDAP Panel could not conclude on the irritation potential of the additive. In absence of data, no conclusion can be reached on the efficacy of tartrazine in freshwater fish baits.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of lutein‐rich extract of Tagetes erecta L. as sensory additive (functional group: Colourants (ii) substances which, when fed to animals, add colours to food of animal origin) for turkeys for fattening. The additive is already authorised for use in feed for chickens for fattening and minor poultry for fattening and laying hens and minor poultry for laying. The FEEDAP Panel concluded that the use of lutein‐rich extract of T. erecta is safe for turkeys for fattening when used up to the maximum proposed use level of 80 mg total carotenoids/kg complete feed. The Panel concluded that the use of lutein‐rich extract of T. erecta in feed for turkeys for fattening under the proposed conditions of use would not be of concern for the consumer, considering also its use in other poultry for fattening and for laying hens. Regarding user safety, the lutein‐rich extract of T. erecta extract is irritant to skin and eyes and any exposure is considered a risk. The conclusions on user safety reached for the lutein‐rich extract of T. erecta would, in principle, apply to preparations made with it. The use of the additive in feed for turkeys for fattening under the proposed conditions of use is safe for the environment. The FEEDAP Panel concluded that the additive has the potential to colour the skin of turkeys for fattening at the proposed conditions of use.

IntroductionAtrial tachycardia (AT) frequently occurs after cardiac surgery or surgical ablation procedures. The novel charge density-based mapping system (CDM) provides global chamber mapping and can detect crucial pathways of conduction; therefore, it has potential added value in catheter ablation (CA) of post-surgical ATs. We aimed to test the hypothesis that CDM-guided CA procedures are safe, feasible, and may improve outcome compared to conventional sequential 3D mapping (CARTO)-based CA.Methods and resultsConsecutive patients undergoing CA for post-surgical AT guided by CDM or CARTO were enrolled. Procedural safety and efficiency were analyzed. Acute success, one-year outcome was assessed. A total of 35 patients (mean age 60.8 ± 10.6 years, 42.9% female) underwent CA of AT using CDM (n = 20) and CARTO (n = 15). A total of 61 ATs were mapped (35 in CDM and 26 in CARTO group). Four patients had focal ATs, 22 macro re-entrant, and 8 patients had ATs with both mechanisms. No differences were found in procedural complication (CDM 3 vs. CARTO 1 patient, p = 0.61). There were no differences in procedure duration (185.9 vs. 147.9 min, p = 0.09), fluoroscopy dose (165.0 vs. 155.0 mGy, p = 0.31), RF application number (28.0 vs. 18.0, p = 0.17) or duration (1,251.5 vs. 1,060.0 s, p = 0.54). Acute success was 95.0% in CDM and 73.3% in CARTO group (p = 0.14). Cumulative AT recurrence rates were lower in CDM group compared to CARTO group (10.0% vs. 46.7%, p = 0.02).ConclusionsThe CDM system is feasible. Our data suggest that patients treated with CDM-guided CA developed fewer AT recurrences as compared to CARTO-guided procedures.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of diclazuril (Clinacox® 0.5%) as a coccidiostat for chickens for fattening and chickens reared for laying. The additive currently on the market complies with the existing conditions of authorisation. The additive remains safe for the target species and the consumer under the authorised conditions of use. The additive is irritant to skin, eyes and respiratory tract but is not a skin sensitiser. Exposure by inhalation cannot be excluded. The FEEDAP Panel cannot conclude on the safety for the environment of diclazuril from Clinacox® 0.5% due to lack of data. Diclazuril from Clinacox® 0.5% at a concentration of 1 mg diclazuril/kg complete feed has the potential to control coccidiosis in chickens for fattening. This conclusion is extended to chickens reared for laying. Development of resistance to diclazuril of field Eimeria spp. strains isolated from chickens should be monitored.

Not available.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on red carotenoid‐rich Paracoccus carotinifaciens NITE SD 00017 for salmon and trout (category: sensory additives; functional group: colourants; substances which when fed to animals add colours to food of animal origin) for the renewal of its authorisation. The applicant provided evidence that the additive complies with the conditions of the authorisation. The Panel concludes that the use of the additive in salmon and trout remains safe for the target species, the consumer and the environment under the authorised conditions of use. When assessing consumer exposure to canthaxanthin and adonirubin at the level of the existing maximum residue limits (MRL) for poultry and the proposed MRL for trout/salmon (5 mg/kg muscle), the exposure of consumers exceeds the acceptable daily intake (ADI) in the population classes toddlers and other children. The Panel considers that there is no need to restrict the use of the additive to fish older than 6 months or of more than 50 g. Red carotenoid‐rich Paracoccus carotinifaciens NITE SD 00017 is not irritant to the skin, but is irritant to the eyes. It is considered a dermal and respiratory sensitiser and any exposure via skin or the respiratory tract is a risk.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of indigo carmine as a colourant feed additive for cats, dogs and ornamental fish. In its previous opinion, the FEEDAP Panel concluded that indigo carmine is safe for cats and dogs at levels up to 250 mg/kg complete feed and for ornamental fish up to 1000 mg/kg complete feed. These conclusions were limited to indigo carmine with a purity of at least 93% colouring matter. For the current assessment, the applicant submitted additional data on the characterisation and on the toxicological profile to support the safety of the additive with the purity of at least 85% colouring matter. Based on the new data submitted, the FEEDAP Panel concludes that indigo carmine (purity of at least 85% colouring matter) is safe for cats and dogs at levels up to 250 mg/kg complete feed and for ornamental fish up to 1000 mg/kg complete feed.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety for the consumer of products from animals fed diets with feed additives containing selenium as an active substance. Based on the limited data set available and the several uncertainties, the FEEDAP Panel concluded that the use of organic selenium at the currently maximum authorised use level of 0.2 mg supplemented selenium from organic sources/kg complete feed (within a maximum of 0.5 mg total selenium/kg complete feed) leads to an exceedance of the UL for all the population categories (except elderly and very elderly), suggesting a concern for consumer safety. It was not possible to conclude on the safety of the currently maximum use level of 0.5 mg total selenium/kg complete feed for all consumer categories. Additional data from studies specifically designed to measure deposition of selenium in tissues and products from animal origin resulting from the use of the different sources of selenium would be required to perform a proper risk assessment.

Not available.

Chimeric antigen receptor T cells (CAR-T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR-T directed against CS1 or B Cell Maturation antigen. We found a decrease in naive T cells and elevated frequencies of exhaustion markers in T cells from treated MM patients. Interestingly, individuals treated with daratumumab display elevated ratios of central memory T cells. CAR-T derived from patients at relapse show reduced in vitro expansion and cytotoxic capacities in response to MM cells compared to those produced at diagnosis. Of note, CAR-T from daratumumab treated patients display intermediate defects. Reduced anti-myeloma activity of CAR T cells from treated patients was also observed in a mouse model. Our findings suggest that T cell defects in MM patients, specifically during relapse, have a major impact on their capacity to generate efficient therapeutic CAR-T. Selecting naive or central memory T cell subsets to generate therapeutic T cells could improve the CAR-T therapy for MM.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the coccidiostat salinomycin sodium (Sacox®) for rabbits for fattening. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of salinomycin sodium (SAL‐Na) from Sacox® does not raise safety concerns for the target species, consumers, users and the environment with regard to the production strain. In the absence of adequate tolerance studies, the FEEDAP Panel could not conclude on the safety of SAL‐Na from Sacox® for rabbits for fattening. The FEEDAP Panel concluded that the additive is safe for the consumer when it is used at the proposed maximum level of 25 mg SAL‐Na/kg complete feed for rabbits and a withdrawal period of 1 day is respected. The following maximum residue limits (MRL) are proposed for the marker residue compound salinomycin (SAL): 0.2 and 0.03 mg SAL/kg for liver and kidney, respectively. The additive is not irritant to skin and eyes but should be considered a potential dermal and respiratory sensitiser. A risk for inhalation toxicity could not be excluded. The use of the SAL‐Na from Sacox® in feed for rabbits for fattening up to the highest proposed level will not pose a risk for the terrestrial and aquatic compartment and ground water. The risk of secondary poisoning can be excluded for worm‐eating birds and mammals, while it cannot be excluded for fish‐eating birds and mammals. The FEEDAP Panel concludes that SAL‐Na from Sacox® at the minimum concentration of 20 mg SAL‐Na/kg complete feed has the potential to control coccidiosis in rabbits for fattening. Development of resistance to SAL‐Na of field Eimeria spp. strains isolated from rabbits for fattening should be monitored.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of monensin sodium (Coxidin®) as a coccidiostat for chickens for fattening, chickens reared for laying, turkeys for fattening and turkeys reared for breeding. The additive currently on the market complies with the existing conditions of authorisation. The FEEDAP Panel concluded that Coxidin® remains safe for turkeys for fattening (up to 16 weeks) and extends this conclusion to turkeys reared for breeding (up to 16 weeks). The Panel was not in the position to confirm that the current maximum authorised level of 125 mg monensin sodium/kg complete feed remains safe for chickens for fattening and chickens reared for laying. The use of monensin sodium from Coxidin® at the corresponding maximum authorised/proposed use levels in the target species is safe for the consumer. The existing maximum residue levels (MRLs) for poultry tissues ensure consumer safety. No withdrawal time is necessary. Both formulations of Coxidin® pose a risk by inhalation. The formulation with wheat bran as a carrier was neither irritant to the skin nor a skin sensitiser but it was irritant to the eyes. In the absence of data, no conclusions could be made on the potential of the formulation containing calcium carbonate to be irritant to skin and eyes and to be a skin sensitiser. The use of monensin sodium from Coxidin® in complete feed for the target species poses no risk for the terrestrial compartments and for sediment. No risk for groundwater is expected. For chickens for fattening the risk for aquatic compartment cannot be excluded, but no risks are expected for the other animal categories. There is no risk of secondary poisoning. Coxidin® is efficacious in controlling coccidiosis at a level of 100 mg/kg complete feed for chickens for fattening and at 60 mg/kg complete feed for turkeys for fattening. These conclusions are extended to chickens reared for laying and turkeys reared for breeding. The Panel noted that there are signs of development of resistance of Eimeria spp. to monensin sodium.

Abstract Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.

Silicon solar cells with both-side full-area passivating hole and electron contacts are viable candidates for application as bottom cells in tandem architectures. In this contribution, cells with poly-Si based contacts at both sides are investigated as a potential upgrade to the emerging i-TOPCon single junction devices featuring a passivating contact (poly-Si(n)/SiOx) only at the rear side and an alternative to the SHJ technology featuring a-Si based full-area passivating hole and electron contacts. We show that a higher thermal budget is needed to mediate between poly-Si(p)/SiOx hole and poly-Si(n)/SiOx electron contact when the same thermal interfacial SiOx is applied. This is addressed by using a PECVD oxide that is adapted to the needs of the hole and/or the electron contact. We present a proof-of-concept poly-Si(n)/SiOx/c-Si/SiOx/poly-Si(n) device with emphasis on a lean process flow. An all-PECVD process sequence for the hole contact, i.e., plasma oxides+i/p-a-Si deposited at 200°C in the same chamber was applied. With co-annealing of the contacts, no additional hydrogenation, and no edge insulation step, we observe no shunting and obtain efficiencies of up to 20.8% for M2 size cells, so far.

Plasma-Enhanced Chemical Vapor Deposition (PECVD) is an attractive tool for TOPCon production, as it enables uniformly in situ doped amorphous silicon (a-Si) and dielectric layer depositions with high throughput. However, a lean process requires in situ interfacial oxide growth in the same tool. In this work, we use Plasma-Assisted N2O Oxidation (PANO) in an industrial kHz direct plasma reactor (centrotherm c.PLASMA) to grow the oxide and deposit in situ phosphorus doped a-Si(n) as well as SiNx on asymmetric lifetime samples. Before optimization, the oxide thickness is non uniform on the wafer, and we show that it correlates with the passivation, the contact resistivity, and the doping profile in n-type TOPCon test structures. The passivation seems to benefit more from moderate in-diffusion in the case with PANO than in the case with thermal oxidation. This is probably due to enhanced field-effect passivation compensating for lower chemical passivation, which likely results from plasma-induced damage. After studying the influence of PANO process parameters on the oxide thickness and uniformity, we optimize them to obtain a non-uniformity as low as ±2% and a recombination current density down to 2.3 fA/cm² on planar wafers.

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of propyl gallate as a technological feed additive for all animal species. In its previous opinions on the safety and efficacy of the product, the FEEDAP Panel could not conclude on the safety for the consumer and on a safe level of propyl gallate for cats. Based on the new data provided, the FEEDAP Panel concluded that propyl gallate at a maximum concentration of 71 mg/kg complete feed is safe for cats. The FEEDAP Panel extrapolated the conclusions on the safety for the target species reached in its previous assessment to other physiologically related species and to all other animal species. Propyl gallate is considered safe for the consumer when used in complete feed for all animal species at the concentrations considered safe for the target species.

Objective The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities.Methods Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors.Results Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (−1.13, 95% CI −2.18 to –0.08); living in Canada (−1.33, 95% CI −2.40 to –0.26 (reference USA)) or the UK (−2.49, 95% CI −3.92 to –1.06); body mass index (−1.08 per SD, 95% CI −1.47 to –0.69); gastrointestinal involvement (−3.16, 95% CI −4.27 to –2.05); digital ulcers (−1.90, 95% CI −3.05 to –0.76); moderate (−1.62, 95% CI −2.78 to –0.45) or severe (−2.26, 95% CI −3.99 to –0.52) small joint contractures; interstitial lung disease (−1.11, 95% CI −1.97 to –0.25); pulmonary arterial hypertension (−2.69, 95% CI −4.08 to –1.30); rheumatoid arthritis (−2.51, 95% CI −4.28 to –0.73); and Sjogren’s syndrome (−2.42, 95% CI −3.96 to –0.88).Conclusion Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

Plotting Poetry 6: The Plot. Storytelling in Verse. Conference Report

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of phenylcapsaicin (aXiphen®) as a zootechnical additive (functional group: physiological condition stabilisers) in feed for chickens for fattening. The additive under assessment, phenylcapsaicin, is safe for chickens for fattening up to the maximum proposed use level of 15 mg/kg complete feed. A margin of safety could not be established. Phenylcapsaicin is not genotoxic. The reference point for phenylcapsaicin derived from a 90‐day repeated dose oral toxicity study in rats is 37.2 mg/kg body weight (bw) per day, the lowest of the model averaged BMDL20 values for alanine aminotransferase increase in plasma. The metabolic similarity in the laboratory animals and the target species was not demonstrated and the identity of the marker residue could not be established. In the absence of such data, the safety for the consumers could not be evaluated. The inhalation exposure of phenylcapsaicin (as liquid) for the user was considered unlikely. The FEEDAP Panel considered the additive irritant to the eyes but not to the skin and it is not a dermal sensitiser. In the absence of appropriate data, the environmental risk assessment for phenylcapsaicin could not be performed. It is unlikely that phenylcapsaicin bioaccumulates in the environment and the risk of secondary poisoning is considered low. The FEEDAP Panel could not conclude on the efficacy of the additive in chickens for fattening at the proposed conditions of use.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of folic acid as a nutritional feed additive. The additive is authorised for use in feed and water for drinking for all animal species. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation and the production process has not been modified. The FEEDAP Panel considers that there is no evidence to revise the conclusions reached in the previous assessment for the safety for the terrestrial species, consumers and for the environment. The use of folic acid in aquatic animal species to cover their nutritional needs is considered safe. However, the Panel is not in a position to set a maximum safe level for all fish and crustacean species. Considering the narrow margin between the requirement and the tolerated levels seen in some aquatic animal species, the FEEDAP Panel considers that supplementation should not exceed the requirements of the different aquatic animal species. The additive is neither a skin irritant nor a dermal sensitiser. The exposure through inhalation is likely. Due to the lack of data, the FEEDAP Panel is not in the position to conclude on the potential of folic acid to be harmful to the respiratory system and irritant to eyes. The Panel retains that the previously made conclusion on the efficacy remains valid.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of zinc chloride hydroxide monohydrate as a nutritional feed additive for all animal species (3b609). The applicant reported changes in the production process and requested a change in the specification of the additive. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) confirms that the use of the additive under the current authorised conditions of use is safe for the target species and the consumers. The use of the additive in animal nutrition at the proposed use levels for the terrestrial species and land‐based aquaculture systems is considered safe for the environment. The FEEDAP Panel cannot conclude on the safety of the additive for marine sediment compartment, when it is used in sea cages. The additive is an eye irritant, but not irritant to the skin and not a skin sensitiser. The exposure through inhalation is likely, but in the absence of data, the Panel is not in a position to conclude on the risk of exposure by inhalation. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

This work aimed at using pulsed laser ablation in water (PLAW) for the production of titanium dioxide nanoparticles in water from a commercially pure titanium target. There is great commercial interest in nanotitania, which can be found in products including paints, coatings, textiles, cosmetics, solar panels, and catalysts. Nevertheless, nanotitania is usually obtained through chemical routes, which are cost-intensive and cause a negative environmental impact. PLAW comes as a cleaner option for obtaining nano-TiO2 since it uses only solid titanium and deionized water as raw materials. After the process, an optical micrography of the Ti targets was carried out to assess the interaction of the laser with the metallic surface. The nanoparticles were characterized by DLS, TEM, Raman, XRD, and UV–Vis. Nano-TiO2 activity as a photocatalyst was tested for the degradation of the dye RR141. TEM images point to two populations of produced nanoparticles: one spherical with average sizes between 8 and 13 nm, and one spindle-like with the major axis average ranging between 17 and 35 nm. Composition analyses with XRD and Raman indicate the formation of anatase, rutile, and amorphous titania. The color of the solution produced was bluish, which may indicate the presence of surface defects that extend the light absorption band to the visible range. The catalysis experiments showed suitable results for the UV spectrum, and the calculated bandgaps were close to that of anatase, around 3.2 eV.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of Cylactin® as zootechnical additive. The active agent of the additive is Enterococcus lactis NCIMB 10415, and three additive formulations currently authorised: Cylactin® LBC G35, Cylactin® LBC ME10 and Cylactin® LBC ME20 plus. The additive is currently authorised in the EU for use in poultry (chickens and minor poultry species for fattening, chickens and minor species reared for laying), calves and kids for rearing and for fattening, sows, suckling and weaned piglets and pigs for fattening. The applicant is now seeking the renewal of its authorisation and the extension of use for chickens and minor poultry species reared for breeding, turkeys for fattening and reared for breeding, ornamental birds, lambs for rearing and for fattening, minor or other ruminants' species for rearing and fattening, minor suckling and weaned Suidae species, pigs and minor Suidae species for fattening, rearing or reproduction. In addition, the applicant is seeking authorisation for use in water for drinking for all above‐mentioned target species and categories. The applicant has provided evidence that the additive currently on the market complies with the conditions of authorisation. The FEEDAP Panel concludes that the additive is safe for the target animals, consumers and the environment under the authorised/new proposed conditions of use. The Cylactin® LBC ME10 and LBC ME20 plus are not skin and eye irritants, but no conclusion could be drawn on the potential of Cylactin® LBC G35 to be skin and eye irritant. Moreover, no conclusions could be drawn on the additive skin sensitisation potential. The additive is considered a potential respiratory sensitiser. The efficacy for the new target species/categories as well its use in water was extrapolated from the previous efficacy studies.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of dicopper chloride trihydroxide as a nutritional feed additive. The additive is currently authorised for use in all animal species (3b409). The applicant is requesting a modification in the current authorising specification: (i) replacing the alpha crystal form paratacamite with clinoatacamite; (ii) removing the ratio between crystal polymorphs from the authorising specification; (iii) changing the minimum for particles below 50 μm from 1% to 5%. The FEEDAP Panel considers that the proposed modifications do not introduce concern for the safety for the target species and that the additive remains safe for the target species and the consumers when used up to the maximum authorised levels. Regarding the safety for the environment, the use of the additive in feed for terrestrial animals and land‐based aquaculture is considered safe under the proposed conditions of use. The data available do not allow the FEEDAP Panel to reach a conclusion on the safety of the additive for marine sediment when it is used in sea cages. The additive is not corrosive to skin, but is an eye and skin irritant. Due to the nickel presence, it is considered a skin and respiratory sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

The objective of this study was to assess the clinical impact and financial costs of next-generation sequencing (NGS) in 5 categories of pediatric and adult hematological cancers. NGS prescriptions were prospectively collected from 26 laboratories, with varied technical and reporting practice (all or only significant targets). Impact was defined by the identification of (1) an actionable mutation, (2) a mutation with prognostic and/or theranostic value, and/or (3) a mutation allowing nosological refinement, reported by local investigators. A microcosting study was undertaken in 4 laboratories, identifying the types and volumes of resources required for each procedural step. Individual index prescriptions for 3961 patients were available for impact analysis on the management of myeloid disorders (two thirds) and, mainly mature B, lymphoid disorders (one third). NGS results were considered to impact the management for 73.4% of prescriptions: useful for evaluation of prognostic risk in 34.9% and necessary for treatment adaptation (actionable) in 19.6%, but having no immediate individual therapeutic impact in 18.9%. The average overall cost per sample was 191 € for the restricted mature lymphoid amplicon panel. Capture panel costs varied from 369 € to 513 €. Unit costs varied from 0.5 € to 5.7 € per kb sequenced, from 3.6 € to 11.3 € per target gene/hot-spot sequenced and from 4.3 € to 73.8 € per target gene/hot-spot reported. Comparable costs for the Amplicon panels were 5–8 € per kb and 10.5–14.7 € per target gene/hot-spot sequenced and reported, demonstrating comparable costs with greater informativity/flexibility for capture strategies. Sustainable funding of precision medicine requires a transparent discussion of its impact on care pathways and its financial aspects.

Objectives Acute myeloid leukemia (AML) with inv(16)/t(16;16) is among the most frequent AML subtypes. It is recognized by the detection of the CBFB-MYH11 fusion which confers a favorable prognosis, irrespective of the presence of secondary cytogenetic abnormalities. However, the effect of additional genetic anomalies on the behavior of inv(16) AML is debatable. Recent case reports describe an unfavorable prognosis for those patients, characterized by early relapse and death. In this study, we present a series of patients with CBFB-MYH11 fusion and high-risk rearrangements to increase knowledge about this potentially distinct subgroup.Methods All cases with inv(16)/ t(16;16) and one or more high risk abnormalities were reviewed at two tertiary healthcare centers between years 2006 and 2020 in terms of demographics, biological and clinical data.Results Among the total 1447 and 1283 AML cases, the frequency was found to be 0,2% and 0.3%. Clinical data could be retrieved for 5 patients. Detected high-risk abnormalities included TP53 and 5q deletion, complex and monosomal karyotype. The median age was 67 years, with a majority of females (M:F = 1:1.5). Two out of 5 patients presented with therapy related AML, with short latency periods. All patients presented with thrombocytopenia and/or leukocytopenia. Bone marrow aspirates revealed atypical morphology and the detection of rare CBFB-MYH11 fusion transcripts. All 5 patients died, with a short mean overall survival of 5.8 months.Discussion and Conclusion Our series suggests that the presence of high risk abnormalities confers distinct biological features and poor prognosis to inv(16) AML.

The purpose of this study was to examine the abilities of athletes with specific gait training (i.e., runners) discriminating personal gait from point-light videos were compared to athletes for whom gait is not a trained aspect of the sport (i.e., swimmers), and that of a control. It was hypothesized that runners would discriminate their gait among different individuals with greater accuracy than the other two groups and that runners would also devote more attention to the lower extremities for recognition indications. Results showed that runners group recognized themselves more often than the other two groups (p = .048, η2 = 0.18), and that runners allotted more visual attention to the lower extremities (p < .05, ηp 2 = 0.16) when viewing the point-light videos than the other groups. The findings were consistent with other investigations with point-light video representations of movement and suggest that experience and training lead to movement self-awareness that is both recognizable and accessible by a performer.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a feed additive consisting of 25‐hydroxycholecalciferol (produced by Pseudonocardia autotrophica DSM 32858) for all pigs, all poultry for fattening and ornamental birds and other poultry species. The production strain P. autotrophica DSM 32858 is not genetically modified however, uncertainties remain on the possible presence of its viable cells in the final product. Due to the lack of adequate safety data and uncertainty on the presence of nano particles, the FEEDAP Panel cannot conclude on the safety of the additive for the target species and the consumer. The additive was shown not to be irritant to skin or eyes and it is not a skin sensitiser. Considering the low dusting potential of the additive, the FEEDAP Panel concluded that the exposure through inhalation is unlikely. However, the FEEDAP Panel considered that uncertainties remain on genotoxicity and on the possible presence of viable cells of P. autotrophica DSM 32858 in the final product which might have an impact on the safety for the users. The use of the feed additive is considered safe for the environment. The Panel concluded that the additive has a potential to be efficacious under the proposed conditions of use.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium ferrocyanide as a technological feed additive, functional group anticaking agents, for all animal species. The additive potassium ferrocyanide is intended to be used in potassium chloride with a maximum content of 150 mg ferrocyanide anion/kg salt. The use of potassium ferrocyanide is safe, when added to potassium chloride at a maximum content of 150 mg ferrocyanide anions (anhydrous)/kg for: pigs for fattening and lactating sows, sheep, goats, salmon and dogs. In the absence of a margin of safety, the use of potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening, laying hens, turkeys, piglets, veal calf, cattle for fattening, dairy cows, horse, rabbit and cats. In the absence of information on the use of potassium chloride in the diets for any other animal species, no conclusion on a potentially safe level of potassium chloride, supplemented with 150 mg ferrocyanide/kg, can be made. The use of potassium ferrocyanide in animal nutrition is of no concern for consumer safety. The results of in vivo studies showed that potassium ferrocyanide is not irritant to skin and eye and is not a skin sensitiser. However, due to the presence of nickel, the additive should be considered as a respiratory and dermal sensitiser. The available data do not allow the FEEDAP Panel to conclude on the safety of the additive for the soil and the marine environment, while the use of the additive in land‐based aquaculture according to the proposed conditions of use is considered of no concern. Potassium ferrocyanide is considered to be efficacious as an anticaking agent when included in potassium chloride at the proposed use levels.

Human platelet lysate (HPL), rich in growth factors, is increasingly recognized for its potential in tissue engineering and regenerative medicine. However, its use in liquid or gel form is constrained by limited stability and handling difficulties. This study aimed to develop dry and porous aerogels from HPL hydrogel using an environmentally friendly supercritical CO2-based shaping process, specifically tailored for tissue engineering applications. The aerogels produced retained their three-dimensional structure and demonstrated significant mechanical robustness and enhanced manageability. Impressively, they exhibited high water absorption capacity, absorbing 87% of their weight in water within 120 min. Furthermore, the growth factors released by these aerogels showed a sustained and favourable biological response in vitro. They maintained the cellular metabolic activity of fibroblasts (BALB-3T3) at levels akin to conventional culture conditions, even after prolonged storage, and facilitated the migration of human umbilical vein endothelial cells (HUVECs). Additionally, the aerogels themselves supported the adhesion and proliferation of murine fibroblasts (BALB-3T3). Beyond serving as excellent matrices for cell culture, these aerogels function as efficient systems for the delivery of growth factors. Their multifunctional capabilities position them as promising candidates for various tissue regeneration strategies. Importantly, the developed aerogels can be stored conveniently and are considered ready to use, enhancing their practicality and applicability in regenerative medicine.

Background and aimA recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists.MethodsThis study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens.ResultsBesides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P

Abstract Chimeric antigen receptor T cells (CAR‐T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR‐T directed against CS1 or B Cell Maturation antigen. We found a decrease in naive T cells and elevated frequencies of exhaustion markers in T cells from treated MM patients. Interestingly, individuals treated with daratumumab display elevated ratios of central memory T cells. CAR‐T derived from patients at relapse show reduced in vitro expansion and cytotoxic capacities in response to MM cells compared to those produced at diagnosis. Of note, CAR‐T from daratumumab treated patients display intermediate defects. Reduced anti‐myeloma activity of CAR T cells from treated patients was also observed in a mouse model. Our findings suggest that T cell defects in MM patients, specifically during relapse, have a major impact on their capacity to generate efficient therapeutic CAR‐T. Selecting naive or central memory T cell subsets to generate therapeutic T cells could improve the CAR‐T therapy for MM.

Abstract Following a request from the European Commission, EFSA was asked to deliver a new scientific opinion on the coccidiostat halofuginone hydrobromide (STENOROL®) when used as a feed additive for chickens for fattening and turkeys for fattening/reared for breeding. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the safety for turkeys for fattening established in its previous opinion can be extended to turkeys for breeding up to 12 weeks of age. Based on the new data provided on the safety for consumer, environment and efficacy, the Panel updates its previous conclusions as follows: halofuginone hydrobromide is not genotoxic. Applying an uncertainty factor of 100 to the lowest no observed adverse effect level (NOAEL) of 0.03 mg/kg body weight (bw) per day, an acceptable daily intake (ADI) of 0.3 μg halofuginone/kg bw is established. The chronic exposure of consumers to residues of halofuginone would amount to 6–19% of the ADI after 3 days of withdrawal. Therefore, the Panel considers that the additive is safe for the consumer of tissues obtained from chickens for fattening and turkeys for fattening fed the additive at a maximum level of 3 mg/kg complete feed at a 3‐day withdrawal time. For control purposes, the Panel recommends the setting of the following maximum residue limits (MRLs): liver, 50 μg/kg; kidney, 40 μg/kg; muscle, 3 μg/kg; skin/fat, 10 μg/kg wet tissue. Based on an updated environmental risk assessment, no concern for groundwater is expected. Halofuginone is unlikely to bioaccumulate and the risk of secondary poisoning is not likely to occur. No safety concerns are expected for terrestrial and aquatic environments. The additive has the potential to control coccidiosis in chickens for fattening and turkeys for fattening/reared for breeding up to 12 weeks of age at a minimum level of 2 mg/kg complete feed.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of potassium and sodium ferrocyanide as technological feed additives for all animal species. The additives sodium‐ and potassium ferrocyanide are intended to be used in sodium chloride with a maximum content of 80 mg ferrocyanide anion (anhydrous)/kg salt. The FEEDAP Panel concluded that the use of sodium ferrocyanide and potassium ferrocyanide is safe, when added to sodium chloride at a maximum content of 80 mg ferrocyanide anion/kg for: turkey for fattening and laying hens and other laying/breeding birds; all porcine species and categories, all ruminant species and categories, rabbit, horse, salmonids and other minor fin fish, dogs and cats. In the absence of a margin of safety, the use of sodium and potassium chloride according to the proposed conditions of use is not considered to be safe for chickens for fattening and other poultry species for fattening or reared for laying/breeding other than turkeys. In the absence of information on the use of sodium chloride in the diets for any other animal species, no conclusion on a potentially safe level of sodium chloride, supplemented with 80 mg ferrocyanide anions (anhydrous)/kg, could be made. The use of sodium and potassium ferrocyanide in animal nutrition under the conditions of use proposed is of no concern for consumer safety. The results of in vivo studies showed that sodium and potassium ferrocyanide are not irritant to skin and eye and are not skin sensitisers. However, owing to the presence of nickel, sodium ferrocyanide, is considered a dermal and respiratory sensitiser. No conclusions could be reached on the safety of the user exposed via inhalation for potassium ferrocyanide. The use of sodium and potassium ferrocyanide as feed additives is considered safe for the environment. The additives are considered to be efficacious as anticaking agents in sodium chloride at the proposed use level.

• Risk stratification of heart transplanted patients with cardiac allograft vasculopathy (CAV) after percutaneous coronary intervention (PCI) remains challenging. • The CAV classification nomenclature of the International Society of Heart and Lung Transplantation (ISHLT) could apply for risk stratification after PCI. • SYNTAX-scores I and II could be complemental for risk stratification and individualization of invasive follow-up of patients after heart transplantation with CAV, before and after PCI. Percutaneous coronary intervention (PCI) might improve outcome at severe stages of cardiac allograft vasculopathy (CAV) among patients after heart transplantation (HTx). Yet, risk stratification of HTx patients after PCI remains challenging. To assess whether the International Society for Heart and Lung Transplantation (ISHLT) CAV classification remains prognostic after PCI and whether risk-stratification models of non-transplanted patients extend to HTx patients with CAV. At 2 European academic centers, 203 patients were stratified in cohort 1 (ISHLT CAV1, without PCI, n = 126) or cohort 2 (ISHLT CAV2 and 3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I, SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). RSXS-I > 0 defined incomplete revascularization (IR). SXS-II predicted mortality in cohort 1 (P = 0.004), whereas SXS-I (P = 0.009) and SXS-II (P = 0.002) predicted mortality in cohort 2. Post-PCI, IR (P = 0.004), high rISHLT (P = 0.02) and highest tertile of rSXS-II (P = 0.006) were associated with higher 5-year mortality. In bivariable Cox analysis, baseline SXS-II, IR and rSXS-II remained predictors of 5-year mortality post-PCI. There was a strong inverse relationship between baseline and rSXS-I (r = -0.55; P < 0.001 and r = -0.50; P = 0.003, respectively) regarding the interval to first reintervention. People with ISHLT CAV classification could apply for risk stratification after PCI. SYNTAX scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV. [Display omitted] Visual Take-Home Graphic Kaplan-Meier curves of post-procedural scores for the endpoint of overall mortality (above) and reintervention (below) in patients after heart transplantation with severe cardiac allograft vasculopathy at 5 years after first PCI. 1, Freedom from overall mortality: 1, A, Freedom from mortality according to residual ISHLT CAV grades. 1, B, Freedom from overall mortality according to dichotomization in complete vs incomplete revascularization (residual SYNTAX score I = 0 vs residual SYNTAX score I > 0).1, C, Freedom from overall mortality according to the tertiles of residual SYNTAX score II. 2, Freedom from reintervention: 2, A, Freedom from reintervention according to residual ISHLT CAV grades. 2, B, Freedom from reintervention according to dichotomization in complete vs incomplete revascularization (residual SYNTAX score I = 0 vs residual SYNTAX score I > 0). 2, C, Freedom from reintervention according to dichotomization in presence of diffuse narrowing vs no presence of diffuse narrowing. P values of log-rank tests are shown. CAV, cardiac allograft vasculopathy; ISHLT, International Society for Heart and Lung Transplantation; rISHLT grade, residual CAV grade according to ISHLT nomenclature; SXS, SYNTAX score; rSXS, residual SYNTAX score; PCI, percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

To survey practices concerning the use of anticoagulants and antiplatelets in microvascular free-flap reconstruction following oncological surgery of the head and neck. A survey of practices was carried out between September 2022 and March 2023. An online questionnaire was sent to members of the French GETTEC Head-and-Neck Tumor Study Group in all French centers practicing head-and-neck cancer surgery with reconstruction using microvascular free-flaps. The questionnaire asked surgeons about their practices regarding the use of intra- and postoperative anticoagulants and antiplatelets, preoperative management of comorbidities, and prevention of postoperative complications. Sixty-one percent of the 38 respondents (23/38) used intraoperative intravenous heparin injection, associated to flap irrigation with heparin for 76% of surgeons (29/38) and/or a heparin solution bath for 37% (14/38). Postoperative anticoagulation was used by 95% of surgeons (36/38), and antiplatelets by 40% (15/38). Postoperatively, 40% (15/38) carried out monitoring using an implantable micro-Doppler probe, associated to analysis of clinical characteristics of the flap. Reconstructive surgery using microvascular free-flaps involves numerous factors that can influence success. Prospective studies, particularly concerning the management of anticoagulants, could enable a national consensus on methods for free-flap reconstruction. [ABSTRACT FROM AUTHOR]