Efficacy of a feed additive consisting of ferrous lysinate sulfate for all animal species (Phytobiotis Futterzusatzstoffe GmbH).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the efficacy of ferrous lysinate sulfate (Plexomin® L-Fe) for all animal species. The additive has not been previously authorised as a feed additive in the European Union (EU). The safety of the additive for the target species, consumer, user and the environment has already been assessed in previous opinions. However, the efficacy remained inconclusive due to the absence of evidence of the bioavailability of the iron contained in the additive in the trials submitted either with chickens for fattening or with weaned piglets. For the present assessment, the applicant submitted a recalculation of the previous data on weaned piglets, which did not show evidence of bioavailability. Therefore, in the absence of adequate data, the FEEDAP Panel could not conclude on the efficacy of ferrous lysinate sulfate for all animal species.

Safety and efficacy of a feed additive consisting of muramidase produced with Trichoderma reesei DSM 32338 (Balancius™) for laying hens (DSM nutritional products).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of muramidase produced with Trichoderma reesei DSM 32338 (Balancius™) as a feed additive for laying hens. The additive is already authorised as a zootechnical additive (functional group: other zootechnical additives) for chickens, turkeys and minor poultry species for fattening or reared for breeding, and for weaned piglets. The enzyme is produced by fermentation with a genetically modified strain of Trichoderma reesei; viable cells of the production strain and its recombinant DNA were not detected in the additive. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive does not give rise to safety concerns regarding the genetic modification of the production strain. Based on the data available from a sub-chronic oral toxicity study, the Panel concluded that the additive is safe for laying hens at the maximum recommended level of 60,000 LSU(F) (muramidase activity units)/kg feed. The Panel also concluded that the additive is safe for the consumers and the environment. The liquid formulation of the additive is considered not irritant to the skin or eyes. The solid formulation of the additive is considered not irritant to the skin. The Panel cannot conclude on the potential of the additive (both formulations) to be a dermal sensitiser or on the potential of the solid formulation to be irritant to the eyes. Due to the proteinaceous nature, both forms of the additive should be considered respiratory sensitisers. The additive has the potential to be efficacious as a zootechnical additive for laying hens at 30,000 LSU(F)/kg feed.

Assessment of the feed additive consisting of Lacticaseibacillus paracasei ATCC PTA-6135 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lacticaseibacillus paracasei ATCC PTA-6135 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the active agent L. paracasei ATCC PTA-6135 remains safe for all animal species, consumers and the environment. Regarding user safety, the panel concluded that owing to the nature of the additive, L. paracasei ATCC PTA-6135 should be considered a potential skin and respiratory sensitiser, and any exposure through the skin and respiratory tract is considered a risk. In the absence of data, no conclusion could be drawn on the eye irritation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study.

Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain. Methods: Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION). Findings: From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes. Interpretation: Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity. Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".

Safety and efficacy of a feed additive consisting of a tincture derived from the leaves of Eucalyptus globulus Labill. (eucalyptus tincture) for all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a tincture from the leaves of Eucalyptus globulus Labill. (eucalyptus tincture) when used as a sensory additive for all animal species. The product is a ■■■■■ solution, with a dry matter content of ~ 1.86%, which contains on average 0.454% phenolic acids and flavonoids (of which 0.280% was gallic acid), 0.0030% 1,8-cineole and 0.00012% methyleugenol. In the absence of analytical data on the occurrence of mono- or diformylated adducts of acylphloroglucinols with terpenes in the tincture and in the absence of toxicity data, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) could not conclude on the use of eucalyptus tincture for long-living and reproductive animals. For short-living animals (species for fattening), the additive was considered of no concern at 4 mg/kg complete feed for chickens for fattening, 5 mg/kg for turkeys for fattening, 6 mg/kg for piglets and rabbits for meat production, 7 mg/kg for pigs for fattening, 16 mg/kg for veal calves (milk replacer), 14 mg/kg for cattle for fattening, sheep/goats and horses for fattening, and 15 mg/kg for salmonids. These levels were extrapolated to physiologically related minor species. No safety concern would arise for the consumer from the use of eucalyptus tincture up to the levels in feed considered of no concern. Eucalyptus tincture should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. The use of eucalyptus tincture as a flavour in animal feed was not expected to pose a risk for the environment. Since the leaves of E. globulus and their preparations were recognised to flavour food and their function in feed would be essentially the same, no demonstration of efficacy was considered necessary.

Safety and efficacy of feed additives consisting of ginkgo tinctures obtained from the leaves of Ginkgo biloba L. for use in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of tinctures obtained from the dried leaves of Ginkgo biloba L. (ginkgo tinctures) when used as sensory additives. The tinctures are water/ethanol solutions with a dry matter content of 5.7% (tincture A) and 3.0% (tincture B). The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additives under assessment are safe for the target species at the following concentrations in complete feed: (i) ginkgo tincture A at 240 mg/kg for horses and 750 mg/kg for dogs; (ii) ginkgo tincture B at 600 mg/kg for horses and 50 mg/kg for all other animal species. No safety concern would arise for the consumer from the use of ginkgo tinctures up to the maximum proposed use level in feed for the target species. The tinctures should be considered as irritants to skin and eyes, and as dermal and respiratory sensitisers. The use of ginkgo tinctures at the proposed use levels in feed for the target species is not considered to be a risk to the environment. While the available data indicate that Ginkgo preparations have a distinctive flavour profile, there is no evidence that ginkgo tinctures would impart flavour to a food or feed matrix. Therefore, the FEEDAP Panel cannot conclude on the efficacy of the additives.

Safety and efficacy of a feed additive consisting of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® Extra) for suckling and weaned piglets and other growing Suidae (Phytobiotics Futterzusatzstoffe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® Extra) as a zootechnical feed additive for suckling and weaned piglets and other growing Suidae. The additive is standardised to contain a concentration of the sum of the four alkaloids sanguinarine, chelerythrine, protopine and allocryptopine of 1.25%, with 0.5% sanguinarine. Owing to the presence of the DNA intercalators sanguinarine and chelerythrine, a concern for genotoxicity was identified. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) had no safety concerns for the target species when the additive is used at the recommended level of 0.750 mg sanguinarine/kg complete feed for suckling and weaned piglets and other growing Suidae. Since in all consumer categories the exposure to sanguinarine and chelerythrine via the use of Sangrovit® Extra exceeds the threshold of toxicological concern of 0.0025 µg/kg bw per day for DNA reactive mutagens and/or carcinogens, the FEEDAP Panel could not conclude on the safety for the consumers. The additive was shown to be irritant to the eyes but not irritant to skin or a skin sensitiser. The FEEDAP Panel could not exclude the potential of the additive to be a respiratory sensitiser. When handling the additive, exposure of unprotected users to sanguinarine and chelerythrine may occur. Therefore, to reduce the risk, the exposure of users should be reduced. The use of Sangrovit® Extra as a feed additive under the proposed conditions of use was considered safe for the environment. The additive Sangrovit® Extra had the potential to be efficacious in improving performance of weaned piglets at 0.600 mg sanguinarine/kg complete feed. This conclusion was extended to suckling piglets and extrapolated to other growing Suidae.

Safety and efficacy of a feed additive consisting of 6-phytase produced with Trichoderma reesei (CBS 126897) (Quantum® Blue) for fin fish (ROAL Oy).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of 6-phytase (Quantum® Blue) as a zootechnical feed additive for fin fish. The additive is authorised for use in poultry and pigs. The additive is available in solid and liquid forms, and the 6-phytase contained in the product is produced by fermentation with a genetically modified strain of Trichoderma reesei. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the genetic modification of the production strain does not give rise to safety concerns; viable cells of the production strain and its DNA were not detected in the final products. The FEEDAP Panel concluded that, based on the data available, the additive tested is safe for fin fish at the highest recommended level of 2500 phytase activity unit (FTU)/kg complete feed. The Panel concluded that Quantum® Blue is not an irritant to skin and eyes nor a skin sensitiser. Owing to the proteinaceous nature of the active substance, 6-phytase (Quantum® Blue) is considered a respiratory sensitiser. The use of Quantum® Blue as a feed additive is considered safe for the environment. The additive is considered to be efficacious as a zootechnical additive for salmonids and ornamental fish at 500 FTU/kg complete feed and other fin fish at 2500 FTU/kg complete feed.

Safety and efficacy of a feed additive consisting of Saccharomyces cerevisiae DSM 34246 (Canobios-BL) for cats and dogs (ACEL pharma s.r.l.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Saccharomyces cerevisiae DSM 34246 as a zootechnical feed additive for dogs and cats. The additive, with the trade name Canobios-BL, is intended for use in feed for cats and dogs at a proposed minimum inclusion level of 5 × 109 CFU/kg complete feed. Saccharomyces cerevisiae is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. Since the identity of the active agent has been clearly established and the additive is composed by dried cells of the active agent and an emulsifier, that are not expected to introduce any risk, the additive is considered safe for the target species. Canobios-BL is not a skin or eye irritant but should be considered a skin and respiratory sensitiser. Canobios-BL is considered to be efficacious in feedingstuffs for dogs and cats at the use level 5 × 109 CFU/kg complete feed.

Efficacy of a feed additive consisting of endo-1,4-beta-xylanase and endo-1,3(4)-beta-glucanase produced with Talaromyces versatilis IMI 378536 and DSM 26702 (ROVABIO® ADVANCE) for weaned piglets (Adisseo France SAS).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the efficacy of ROVABIO® ADVANCE (liquid and solid) which contains endo-1,4-beta-xylanase and endo-1,3(4)-beta-glucanase produced with Talaromyces versatilis IMI 378536 and DSM 26702 as a zootechnical feed additive for weaned piglets at the recommended use level of 1800 U xylanase and 1250 U glucanase per kg feed. In a previous assessment, three long-term trials in weaned piglets were submitted. Two of them were considered to support the efficacy of the additive while a third trial was not further considered due to the large number of veterinary treatments applied. A new trial was provided to support the efficacy of the additive, but it did not show a significant improvement of the performance parameters at the minimum recommended use level. Due to the lack of sufficient data, the FEEDAP Panel is not in the position to conclude on the efficacy of the additive for the target species.

Safety of the feed additive consisting of endo-1,4-ß-xylanase (produced with Trichoderma reesei CBS 143953), subtilisin (produced with Bacillus subtilis CBS 143946) and α-amylase (produced with Bacillus amyloliquefaciens CBS 143954) (Avizyme® 1505) for all poultry species (Danisco (UK) Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of the feed additive consisting of endo-1,4-ß-xylanase (produced with Trichoderma reesei CBS 143953), subtilisin (produced with Bacillus subtilis CBS 143946) and α-amylase (produced with Bacillus amyloliquefaciens CBS 143954) (Avizyme® 1505) as a zootechnical feed additive for all poultry species. The additive is authorised in feed for chickens and turkeys for fattening, ducks and laying hens. In 2020, the FEEDAP Panel issued an opinion for the renewal of the authorisation of the additive for the species/categories for which there is an authorisation, a reduction of the minimum recommended level in turkeys for fattening and the extension of use to all poultry species. In that assessment, the Panel could not conclude on the safety of the additive due to uncertainties on the characterisation of the production strains and the possible presence of their viable cells and DNA in the final product. Moreover, limitations were identified in the xylanase specifications and xylanase method of analysis. The applicant submitted information to address the limitations previously identified. The Panel concluded that the additive is safe for the target species under the proposed conditions of use. The use of Avizyme® 1505 in animal nutrition is considered safe for the consumer and the environment. The additive is a mild irritant to skin and eyes; it is not a dermal sensitiser but should be considered a respiratory sensitiser. The additive is efficacious in ducks at 75 U endo-1,4-ß-xylanase, 1000 U subtilisin and 100 U α-amylase/kg of complete feed. In other poultry species for fattening (including turkeys), reared for breeding and reared for laying, the additive is efficacious at 187.5 U endo-1,4-ß-xylanase, 2500 U subtilisin and 250 U α-amylase per kg of complete feed and at 300 U endo-1,4-ß-xylanase, 4000 U subtilisin and 400 U α-amylase per kg of complete feed for all poultry species for laying (except for ducks).

Assessment of the feed additive consisting of l-cystine for all animal species for the renewal of its authorisation (Bretagne Chimie Fine [BCF Life Sciences]).

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 l-cystine as nutritional feed additive. The additive is authorised for use in all animal species (3c391). The applicant has provided evidence that the additive currently in the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed concluded that the use of the feed additive in animal nutrition remains safe for the target species, the consumers and the environment. As regards the safety for the user, l-cystine is not an irritant to skin or eyes and is not a skin sensitiser. Exposure by inhalation of persons handling the additive cannot be excluded. The present application for the renewal of the authorisation does not include any modification proposal that would have an impact on the efficacy of the additive and therefore there is no need for reassessing the efficacy.

Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm3 to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m2/year, with no significant difference between treatment arms (difference deferred - immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m2). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.

Safety and efficacy of a feed additive consisting of a tincture derived from the flowers of Syzygium aromaticum (L.) Merr. & L.M. Perry (clove tincture) for all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a tincture from the dried flower bud of Syzygium aromaticum (L.) Merr. & L.M. Perry (clove tincture) when used as a sensory additive in feed and water for drinking for all animal species. The product is a ■■■■■) solution, with a dry matter content of ~ 1.66%. The product contains on average 0.511% phenolic acids (of which 0.0344% were flavonoids), 0.039% eugenol, 0.00019% methyleugenol and 0.00008% estragole. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of clove tincture is very unlikely to be of safety concern for the target species up to the maximum proposed use level of 50 mg clove tincture/kg complete feed for all animal species, except for horses, for which the proposed use level is 200 mg/kg complete feed. The FEEDAP Panel considers that the use in water for drinking alone or in combination with use in feed should not exceed the daily amount that is considered very unlikely to be of safety concern when consumed via feed alone. No safety concern would arise for the consumer and the environment from the use of clove tincture up to the maximum proposed use levels in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. When handling the additive, exposure of unprotected users to methyleugenol and estragole may occur. Therefore, to reduce the risk, the exposure of the users should be minimised. Since the flower buds of S. aromaticum and their preparations were recognised to flavour food and their function in feed would be essentially the same, no demonstration of efficacy was considered necessary.

Safety and efficacy of a feed additive consisting of an essential oil obtained from the wood of Juniperus deppeana Steud. (cedarwood Texas oil) for use in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from the wood of Juniperus deppeana Steud. (cedarwood Texas oil), when used as a sensory additive for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the essential oil under assessment is safe up to the maximum proposed use levels in complete feed of 15 mg/kg for veal calves (milk replacer), cattle for fattening, sheep, goats, horses, dogs, salmonids and ornamental fish. For the other species, the calculated safe concentrations in complete feed were 5 mg/kg for chickens for fattening, 8 mg/kg for laying hens, 7 mg/kg for turkeys for fattening, 10 mg/kg for piglets, 12 mg/kg for pigs for fattening, 14 mg/kg for sows and dairy cows, 8.5 mg/kg for rabbits and 4 mg/kg for cats. These conclusions were extrapolated to other physiologically related species. For any other species, the additive was considered safe at 4 mg/kg complete feed. The use of cedarwood Texas oil in water for drinking was considered safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. No concerns for consumers and the environment were identified following the use of the additive up to the maximum proposed use level in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a skin and respiratory sensitiser. Since the individual components of cedarwood Texas oil are recognised to flavour food and their function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles.

Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and the non-virulent Newcastle disease virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived PBT cell cultures and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, the analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of the identified expression profiles was further validated in vitro by screening additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique expression profiles. Such profiles may hold promise for future OV preselection with effective oncolytic potency in a specific tumor, therewith potentially improving OV responses.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

BACKGROUND: The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet. METHODS: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. RESULTS: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS. CONCLUSION: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain.

OBJECTIVES: Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more [or resistance to two or more plus contraindication to one or more] core ART classes) and limited treatment options (LTOs) in Spain. METHODS: This was an observational, retrospective, multicentre, cross-sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load [HIV-RNA >200 copies/mL], treatment-limiting drug-drug interaction [DDI], or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR-associated variables. RESULTS: Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/µL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non-nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%). CONCLUSIONS: The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.

Assessment of the feed additive consisting of Pediococcus pentosaceus DSM 14021 for all animal species for the renewal of its authorisation (Chr. Hansen A/S).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Pediococcus pentosaceus DSM 14021, a technological additive for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the Panel considers that any exposure through skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.