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- Familial Hypercholesterolaemia In Children And Adolescents: A European Atherosclerosis Society Consensus StatementPublication . Wiegman, Albert; Bourbon, Mafalda; Freiberger, Tomas; Gidding, Samuel S; Greber-Platzer, Susanne; Groselj, Urh; Holven, Kirsten B.; Hudgins, Lisa C.; Humphries, Steve E.; Hutten, Barbara A.; Ibarretxe, Daiana; Pederiva, Cristina; Peretti, Noel; Raal, Frederick J.; Ramaswami, Uma; Sanin, Veronika; Santos, Raul D.; Steinhagen-Thiessen, Elisabeth; Watts, Gerald F.; Perkins, Rosie; Benn, Marianne; Binder, Christoph J.; Romeo, Stefano; Lennep, Jeanine E. Roeters vanFamilial hypercholesterolaemia (FH) is a common genetic disorder characterized by lifelong elevated LDL cholesterol (LDL-C) concentrations. FH exists in two forms: heterozygous FH (HeFH), which affects around 1 in 300 people worldwide, and homozygous FH (HoFH), which affects around 1 in 300 000. Individuals with FH are at increased risk of premature atherosclerotic cardiovascular disease (ASCVD) and death, and those with HoFH are, if untreated, at extreme risk of ASCVD manifestations even before adulthood. Early diagnosis and treatment in childhood can extend or normalize life expectancy, but limited awareness, underdiagnosis, and undertreatment remain major challenges. This consensus statement aims to address these challenges, supported by increased knowledge of the pathogenesis of FH and the availability of an increasing range of lipid-lowering therapies (LLTs) that can be used from early ages. To increase the detection rate of FH, all countries are encouraged to establish a paediatric screening programme and, given that current diagnostic criteria often fail to identify children with an FH-causing genetic variant, revised diagnostic criteria are presented. Updated LDL-C treatment goals are proposed, and the importance of starting LLTs before puberty in children with HeFH, and, if needed, from 6 years, is highlighted. Guidance on how to manage FH is provided, including treatment algorithms for use in children with either HeFH or HoFH and a discussion on how to promote a smooth transition to adult care. Early detection and optimal treatment as advocated in this consensus statement are crucial to improving life expectancy for children and adolescents with FH.
- Lynch Syndrome: An update of underlying molecular mechanisms, phenotypes and methods to classify variants of uncertain significancePublication . Rodrigues, Paulo; Matos, Paulo; Gonçalves, João; Jordan, PeterIn 2022, colorectal cancer (CRC) was the third most common type of cancer worldwide and the second most common in Europe. CRC ranked as the second leading cause of cancer-related deaths both worldwide and in Europe, with 904,019 and 247,966 deaths, respectively. The majority of CRC cases are sporadic (60–75%); however, 10–35% of CRC are estimated to result from the interaction of heritable and environmental factors. Among these, 5–6% are caused by inherited variants in genes that predispose to the development of CRC. Among the known inherited causes, Lynch Syndrome (LS), formerly known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is the most frequent and accounts for approximately 3% of all CRC. Here we review and update on multiple aspects of LS in the context of CRC, including its genetic and molecular basis, current guidelines for molecular screening and variant classification. Furthermore, we review functional assays that have been used to determine the biological impact of genetic variants of uncertain significance (VUS) and discuss future perspectives in the field.
- Re‐evaluation of sucralose (E 955) as a food additive and evaluation of a new application on extension of use of sucralose (E 955) in fine bakery waresPublication . EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Reginald; Fernandez, Maria Jose Frutos; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Batke, Monika; Dourus, Antonios; Chipman, James; Crebelli, Riccardo; Fürst, Peter; Halldorsson, Thorhallur; Mirat, Manuela; Mortensen, Alicja; Wright, Matthew; Lindtner, Oliver; Barmaz, Stefania; Civitella, Consuelo; Horvath, Zsuzsanna; Levorato, Sara; Mazzoli, Elena; Rasinger, Josef Daniel; Rincon, Ana Maria; Smeraldi, Camilla; Tard, Alexandra; Lodi, FedericaThe present opinion deals with the re‐evaluation of sucralose (E 955) as food additive and with the safety of a proposed extension of use in food category (FC) 7.2 ‘Fine bakery wares’. Based on the available data, no safety concerns arose for genotoxicity of sucralose (E 955) and its impurities and degradation products. Based on the weight of evidence (WoE), the Panel considered the decrease in body weight observed in rats as the relevant endpoint for the derivation of a reference point (RP). The Panel performed a benchmark dose (BMD) analysis on the data from the longest study (combined chronic and carcinogenicity study) with a modified benchmark dose response to account for the poor palatability of sucralose. The resulting RP was 55 mg/kg bw per day (benchmark dose lower confidence limit; BMDL). The Panel considered it appropriate to derive chemical‐specific assessment factor for sucralose and concluded that there is no need to revise the current ADI of 15 mg/kg bw per day of sucralose (E 955) previously established by the Scientific Committee on Food. The exposure estimates considering the currently authorised uses did not exceed the ADI. Therefore, the Panel concluded that there is no safety concern at the reported uses and use levels of sucralose (E 955). The overall exposure did not increase substantially when considering the proposed extension of use. However, based on the available data and the identified uncertainties regarding the potential formation of chlorinated compounds under the wide range of baking processes that may be applicable for FC 7.2, the Panel could not conclude on the safety of the proposed extension of use of E 955 in this FC. The Panel issued recommendations to the European Commission, primarily to consider a revision of the EU specifications for sucralose.
- Scientific opinion on the amendment of the specifications for vegetable carbon (E 153) as a food additivePublication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Furst, Peter; Gaffet, Eric; Loeschner, Katrin; Mast, Jan; Mirat, Manuela; Oomen, Agnes; Undas, Anna; Mech, Agnieszka; Smeraldi, Camilla; Rincon, Ana MariaThe food additive vegetable carbon (E 153) was re‐evaluated by the EFSA ANS Panel in 2012. During that re‐evaluation, data gaps were identified, in particular with respect to impurities and particle characterisation. Following a European Commission call for data to address these gaps, one interested business operator (IBO) submitted analytical data on toxic elements, polycyclic aromatic hydrocarbons (PAHs) and particle size distribution of commercial samples of E 153. The present opinion deals with the assessment of the data provided by the IBO in response to the European Commission call. Based on the analytical data provided, the Panel concluded that the information on toxic elements supports a revision of the current EU specification limits for arsenic, cadmium, mercury and lead, and the introduction of a limit for aluminium. Regarding PAHs, the Panel assessed the risks associated with benzo[a]pyrene and PAH4 under several scenarios and concluded that the resulting margins of exposure (MOE) were above the level of concern but recommended lowering the current limit for benzo[a]pyrene and introducing a limit for PAH4 in the EU specifications for E 153. For what concerns the data on particle size distribution and morphology, the Panel considered that, due to methodological limitations, these data did not allow a full characterisation of the materials used as a food additive and did not adequately support an amendment of the specifications in relation to particle properties. Nevertheless, the Panel concluded that a fraction of small particles, including nanoparticles, is present in vegetable carbon (E 153) and noted that the substance is insoluble in water. Therefore, in line with the EFSA Guidance on Particles‐TR, the Panel concluded that the risk assessment of E 153 performed by the EFSA ANS Panel in 2012 should be complemented with nanoscale considerations.
- Safety evaluation of pectin‐rich extract derived from Coffea arabica as food additivePublication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Barat Baviera, José Manuel; Degen, Gisela; Gott, David; Leblanc, Jean-Charles; Moldeus, Peter; Waalkens-Berendsen, Ine; Wölfle, Detlef; Mech, Agnieszka; Tard, Alexandra; Zakidou, Panagiota; Ruggeri, LauraThe EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety assessment of the proposed use of pectin rich extract derived from Coffea arabica L. as a food additive. The proposed food additive consists of 70%–85% dietary fibres (of which the major part is pectin), 4%–6.5% proteins and substances of potential concern including caffeine, chlorogenic acid, ■■■■■, caffeic acid, ■■■■■, trigonelline. The Panel integrated all available information including existing EFSA evaluations on pectins, coffee fruit pulp, and conducted a new quantitative structure–activity relationship (QSAR) analysis for the substances of potential concern. Studies from literature confirmed that the pectins are not absorbed intact but extensively fermented by intestinal microbiota. No adverse effects were reported in two 90‐day toxicity studies in rats up to 7.8 g/kg body weight (bw) per day and in one human study on sugar beet pectin at 0.2 g/kg bw per day for 4 weeks. The calculated MOE for ■■■■■ indicated that there is a low concern from a public health point of view. The Panel considered that the exposure to caffeine, caffeic acid, ■■■■■, chlorogenic acid, ■■■■■ and trigonelline from use of the proposed food additive would contribute only to a minimal increase over existing dietary exposure and is not of safety concern. Considering the composition of the proposed food additive, the absence of genotoxic concern of its components and lack of adverse effects of the major component (i.e. pectins), the Panel considered that there was no need for a numerical acceptable daily intake. The Panel concluded that the use of pectin‐rich extract derived from Coffea arabica as a new food additive does not raise a safety concern at the proposed use and use levels.
- Sand Quality on Portuguese Blue Flagged Beaches: Fungal and Faecal Contamination Across Two Bathing SeasonsPublication . Silva, Ana Margarida; Sarioglou, Konstantina; das Neves Pereira da Silva, Susana; Viegas, Carla; Ribeiro, Edna; Rebelo, Maria Teresa; Brandão, JoãoThere is growing concern about the quality of sand on beaches, as users tend to spend most of their time on the sand rather than in the water. Numerous pathogenic agents have reportedly been isolated from sand, including bacteria, nematodes and opportunistic fungi. The ability of sand to retain pollutants and facilitate the transmission of pathogens raises public health concerns. We analysed sand-monitoring data from the 2024 and 2025 bathing seasons on Blue Flag beaches to find trends and patterns in total fungal counts, enterococci, and E. coli. The values recorded for microorganisms showed considerable variability, which may reflect the possible combined influence of multiple climatic, environmental, and anthropogenic factors contributing to their presence in beach sand. Our findings suggest that the total fungal count on coastal beaches may be influenced by periods of rainfall, which increases the fungal load in the sand. Values recorded from inland beaches vary considerably between beaches which may reflect the influence of local environmental characteristics, particularly vegetation and beach morphology, although the smaller number of inland samples also makes it difficult to define clear patterns and consistent reference values for this parameter. Bacterial indicators may be particularly influenced by occasional anthropogenic disturbances and contamination events. This study adds significantly to the understanding of the microbiological quality of beach sand, encouraging the integration of sand monitoring into environmental surveillance and management programmes.
- Core Measure Set for Patient Safety in Perioperative Care: A Clinical Practice-Oriented Consensus StudyPublication . Nunes, Ana Beatriz; Teixeira, José Pedro; Leite, Andreia; Schäfer, Willemijn; Valli, Claudia; Martínez-Nicolas, Ismael; Paixão, Margarida; Seyfulayeva, Ayshe; Abelenda, Daniel Treviño; Rodríguez, Anna; Carvalho, Pedro Casaca; Heideveld-Chevalking, Anita; Emond, Yvette; Põlluste, Kaja; Calsbeek, Hiske; Arnal-Velasco, Daniel; Žaludek, Adam; Garel, Pascal; Wagner, Cordula; Groene, Oliver; Orrego, Carola; Sousa, Paulo; SAFEST Scientific Advisory Group; SAFEST Scientific Executive Group; SAFEST ConsortiumObjectives: To develop a consensus-based EU-wide Core Measure Set (CMS), including patient-reported measures, for evaluating perioperative patient safety in routine adult care. Methods: A four-phase approach was applied: 1) identification of candidate structure, process, and outcome measures through three literature reviews; 2) synthesis into an initial list via deduplication and merging; 3) consensus process using a two-round modified eDelphi technique, with subject-matter and lived-experienced experts rating the importance and feasibility of each measure (consensus: ≥75% rating 7–9, ≤15% rating 1–3), followed by an online Consensus Conference addressing measures highly valued by patients but lacking feasibility consensus; 4) refinement of the CMS for patient safety in perioperative care (CMS-PSPC). Results: Out of 9,717 records identified, 340 studies were included, yielding 1,305 measures. After refinement, 247 measures were consolidated; 84 reached consensus, and ten more were added via the Consensus Conference. The final CMS-PSPC comprised 76 measures: 22 outcome, 18 process, and 36 structure measures. Conclusion: The CMS-PSPC provides a standardised, patient-centred framework for evaluating, monitoring and benchmarking perioperative patient safety in routine clinical care, supporting EU-wide quality improvement efforts.
- The p.Ala1035Val variant in Niemann–Pick type C1: Clinical and molecular characterization in Brazilian and Portuguese patients suggests a shared founder effectPublication . Alegretti, Ana Paula; Hammerschmidt, Tatiane; Ribeiro, Isaura; Quelhas, Dulce; Polese-Bonato, Márcia; Saraiva-Pereira, Maria Luiza; Martins, Esmeralda; Guigliani, Roberto; Encarnação, Marisa; Alves Sandra; Regla Vargas, CarmenIntroduction: Niemann–Pick disease type C1 (NPC1, OMIM 257220) is a rare, progressive, and fatal autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NPC1 gene. These variants disrupt intracellular lipid trafficking, leading to the accumulation of cholesterol and glycosphingolipids and resulting in severe, multisystem dysfunction for which no cure currently exists. Materials and methods: To investigate the potential founder effect and shared ancestry of the p.Ala1035Val variant, we analyzed 30 genetically confirmed NPC1 cases, comprising 18 Brazilian (12 of whom were homozygous) and 12 Portuguese participants (3 of whom were homozygous), each carrying at least one p.Ala1035Val allele. Diagnosis was established by clinical evaluation, biochemical assays, and filipin staining, with molecular confirmation by NPC1 genotyping. Results: All analyzed individuals exhibited a conserved haplotype across the SNVs in exons 6 (c.644 A > G, p.His215Arg), 12 (c.1926G > C, p.Ile642Met), 17 (c.2572 A > G, p.Ile858Val), and 18 (c.2793C > T, p.Asn931=), strongly supporting a shared founder effect consistent with an Iberian-associated ancestral background. Among Brazilian (n = 14), visceral involvement occurred in 10/14 (71.4%), predominantly hepatosplenomegaly (6/14, 42.9%), and developmental/cognitive alterations in 10/14 (71.4%), followed by ataxia or gait disturbance in 4/14 (28.6%). Among the Portuguese (n = 3), all presented with visceral involvement, characterized by hepatosplenomegaly (3/3, 100%); one had developmental delay (1/3, 33.3%), and none exhibited ataxia/gait disturbance. Despite the small sample size, clinical patterns appeared similar between the two groups, with differences likely reflecting sampling variability. Discussion: These findings expand the known variant spectrum of NPC1 in Brazilian and Portuguese populations, supporting a possible founder effect resulting from Portuguese colonisation. They also highlight the clinical value of haplotype analysis as a tool for tracing disease origin and improving stratification in medical settings. Furthermore, they emphasise the importance of refining early diagnostic strategies to optimise patient management and improve outcomes in NPC, while highlighting the need for larger, multicenter studies to corroborate this hypothesis and refine its clinical and genetic implications.
- Gender-based violence against women and girls aged ≥15 years presenting to European emergency departments: a multinational, cross-sectional analysisPublication . Carannante, Anna; Pitidis, Alessio; Fondi, Gianni; Fian, Tabea; Alves, Tatiana; Valkenberg, Huib; Nijman, Susanne; Giustini, Marco; IDB groupBackground: Gender-based violence (GBV) is an important public health issue in Europe, yet standardised cross-national data remain scarce. Emergency departments (EDs) are often the first point of contact for an individual who has been assaulted. This study aimed to analyse GBV-related ED presentations using data from the European Injury Database (IDB). Methods: This cross-sectional study analysed IDB data from 16 European countries (Jan 1, 2008, to Dec 14, 2023), defining GBV as intentional injuries inflicted by male perpetrators, involving female individuals aged ≥15 years. Descriptive analyses compared GBV with other female injuries (female victims in whom the perpetrator was recorded as female or was not specified). Multivariable logistic regression assessed GBV-associated injury severity compared with other violence against girls and women, adjusting for age, period, and country. Findings: Of 5 643 295 injury-related ED attendances, 1 960 096 were other female injuries and 21 048 were violence cases, of which 10 315 were GBV. Mean age was 38·2 years (SD 15·7) for individuals subjected to GBV and 55·3 years (41·5) for those with other female injuries. There were higher rates of head and face injuries, contusions, and asphyxiation-related injuries in cases of GBV than other female injuries, but there were lower rates of fractures. Most GBV events occurred in domestic settings (5802 [56·3%] of 10 315 GBV cases) and during night-time hours (3931 [41·9%]), involving physical force (7340 [73·1%]); perpetrators were most commonly intimate partners (4906 [47·6%]) or strangers (1546 [15·0%]). Hospital admission was more frequent in GBV than in other female injuries (2210 [21·4%] of 10 315 vs 366 765 [18·7%] of 1 960 096; p<0·0001). GBV was associated with higher injury severity compared with other female injuries after adjustment (odds ratio 1·22, 95% CI 1·12-1·34; p<0·0001). Interpretation: GBV-related ED cases show distinct features that characterise the visible spectrum of violence against girls and women in emergency settings. These patterns highlight the need for improved documentation and greater awareness of less visible presentations. Cross-national variability underscores the need for harmonised surveillance protocols to capture the true burden of GBV in Europe.
- Predicted no effect concentrations of antifungals for wastewater management and agricultural usePublication . Gil, D.; José, S.; Ascenso, A.; Babič, M. Novak; Segal, E.; Meletiadis, J.; Gangneux, J.P.; Weiskerger, C.J.; Solo-Gabriele, H.M.; Valério, E.; Brandão, J.Antifungal resistance is an on-growing public health concern due to the difficulty in managing or treating medical conditions that often favour fatal fungal infections. The changing climate and globalisation, which increase fungal persistence and propagation, adds to that concern. Wastewater disposal is one potential source to the environment as antifungals are released into it. Considering that most fungal infections originate from the environment and considering the One Health principle, introducing antifungals through wastewater effluents has the potential to promote the emergence and dissemination of antifungal resistance. The objective of this study was to generate knowledge that can assist regulating the release of antifungals in the environment by quantifying predicted no-effect concentrations (PNECs) that would not promote antifungal resistance. For this purpose, a systematic review was performed to consolidate information on antifungals released to the environment and respective concentrations. The systematic literature review followed Preferred Reporting Items for Systematic literature reviews and Meta Analyses extension for Scoping Reviews (PRISMA-SLR). The analysis of 122 reviewed articles using this approach showed high concentrations and dispersion of antifungals in water, wastewater or soil. This highlights their potential dispersion in the environment, thus increasing the potential of fungal antimicrobial resistance. Due to the lack of PNEC values using fungi as model organisms in this review, PNECs for 17 antifungals were calculated using as model, as it is done for clinical purposes. We consider that the antifungal PNECs calculated and consolidated from the literature can be used to prioritise them for regulation and to determine acceptable levels in wastewater effluents.