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Background: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023., Methods: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths., Findings: Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period., Interpretation: Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures., Funding: US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests GD reports that the predecessor of the organisation he works for, Public Health England, received an unrestricted grant from GSK to undertake a study on the outcome of patients who received parenteral zanamavir. The funder received data and interim reports from Public Health England but did not influence analysis and reporting of the study. GD had no involvement in the GSK-funded study on parenteral zanamavir. Furthermore, the currently submitted work was part of the public health response activities to COVID-19 and had no relationship to GSK or the study on parenteral zanamivir. EP has received a personal grant from the Finnish Medical Foundation for PhD studies. JM declares that Public Health Scotland received funding from the EU Horizon 2020 programme for work in describing the epidemiology of COVID-19 and its impact on primary and secondary care as a partner in the IMOVE-COVID-19 project. MK declares having received consulting fees from Gilead Sciences for advising on development of a clinical module for collection of patient-reported outcome data from people living with HIV, and having received an honoraria from GESIDA for speaking at an annual conference on patient-reported outcome measures for people with HIV. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Evidence suggests that drug-coated balloons may benefit in-stent restenosis (ISR) treatment. However, the efficacy of new-generation sirolimus-coated balloon (SCB) compared with the latest generation drug-eluting stents (DESs) has not been studied in this setting., Methods: All patients in the EASTBORNE (The All-Comers Sirolimus-Coated Balloon European Registry) and DEB-DRAGON (DEB vs Thin-DES in DES-ISR: Long Term Outcomes) registries undergoing percutaneous coronary intervention for DES-ISR were included in the study. The primary study end point was target lesion revascularization at 24 months. Secondary end points were major adverse cardiovascular events, all-cause death, myocardial infarction, and target vessel revascularization at 24 months. Our goal was to evaluate the efficacy and safety of SCB versus thin-struts DES in ISR at long-term follow-up., Results: A total of 1545 patients with 1679 ISR lesions were included in the pooled analysis, of whom 621 (40.2%) patients with 621 lesions were treated with thin-strut DES and 924 (59.8%) patients with 1045 lesions were treated with SCB. The unmatched cohort showed no differences in the incidence of target lesion revascularization (10.8% versus 11.8%; P =0.568); however, there was a trend toward lower rates of myocardial infarction (7.4% versus 5.0%; P =0.062) and major adverse cardiovascular events (20.8% versus 17.1%; P =0.072) in the SCB group. After propensity score matching (n=335 patients per group), there were no significant differences in the rates of target lesion revascularization (11.6% versus 11.8%; P =0.329), target vessel revascularization (14.0% versus 13.1%; P =0.822), myocardial infarction (7.2% versus 4.5%; P =0.186), all-cause death (5.7% versus 4.2%; P =0.476), and major adverse cardiovascular event (21.5% versus 17.6%; P =0.242) between DES and SCB treatment., Conclusions: In patients with ISR, angioplasty with SCB compared with thin-struts DES is associated with comparable rates of target lesion revascularization, target vessel revascularization, myocardial infarction, all-cause death, and major adverse cardiovascular events at 2 years., Competing Interests: None.

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients., Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb., Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4., Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment., (© 2024 John Wiley & Sons Ltd.)

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years, the oak lace bug, Corythucha arcuata, has emerged as a significant threat to European oak forests. This species, native to North America, has in the last two decades rapidly extended its range in Europe, raising concerns about its potential impact on the continent's invaluable oak populations. To address this growing concern, we conducted an extensive study to assess the distribution, colonization patterns, and potential ecological niche of the oak lace bug in Europe. We gathered 1792 unique presence coordinates from 21 Eurasian countries, utilizing diverse sources such as research observations, citizen science initiatives, GBIF database, and social media reports. To delineate the realized niche and future distribution, we employed an ensemble species distribution modelling (SDM) framework. Two future greenhouse gas scenarios (RCP 4.5 and RCP 8.5) were considered across three-time intervals (2021-2040, 2061-2080, and 2081-2100) to project and evaluate the species' potential distribution in the future. Our analysis revealed that significant hotspots rich in host species occurrence for this invasive insect remain uninvaded so far, even within its suitable habitat. Furthermore, the native ranges of Turkey oak (Quercus cerris L.) and Hungarian oak (Quercus frainetto L.) species offer entirely suitable environments for the oak lace bug. In contrast, the pedunculate oak and sessile oak distribution ranges currently show only 40 % and 50 % suitability for colonization, respectively. However, our predictive models indicate a significant transformation in the habitat suitability of the oak lace bug, with suitability for these two oak species increasing by up to 90 %. This shift underlines an evolving landscape where the oak lace bug may exploit more of its available habitats than initially expected. It emphasises the pressing need for proactive measures to manage and stop its expanding presence, which may lead to a harmful impact on the oak population across the European landscape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies., (© 2024. The Author(s).)

Objectives: Gender difference in the outcome after type A aortic dissection (TAAD) surgery remains an issue of ongoing debate. In this study, we aimed to evaluate the impact of gender on the short- and long-term outcome after surgery for TAAD., Methods: A multicentre European registry retrospectively included all consecutive TAAD surgery patients between 2005 and 2021 from 18 hospitals across 8 European countries. Early and late mortality, and cumulative incidence of aortic reoperation were compared between genders., Results: A total of 3902 patients underwent TAAD surgery, with 1185 (30.4%) being females. After propensity score matching, 766 pairs of males and females were compared. No statistical differences were detected in the early postoperative outcome between genders. Ten-year survival was comparable between genders (47.8% vs 47.1%; log-rank test, P = 0.679), as well as cumulative incidences of distal or proximal aortic reoperations. Ten-year relative survival compared to country-, year-, age- and sex-matched general population was higher among males (0.65) compared to females (0.58). The time-period subanalysis revealed advancements in surgical techniques in both genders over the years. However, an increase in stroke was observed over time for both populations, particularly among females., Conclusions: The past 16 years have witnessed marked advancements in surgical techniques for TAAD in both males and females, achieving comparable early and late mortality rates. Despite these findings, late relative survival was still in favour of males., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts., (© 2024. The Author(s).)

Background: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention., Methods and Results: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 μV and <60 μV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 μV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P =0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit., Conclusions: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Background: Morganella spp are opportunistic pathogens involved in various infections. Intrinsic resistance to multiple antibiotics (including colistin) combined with the emergence of carbapenemase producers reduces the number of active antimicrobials. The aim of this study was to characterise genetic features related to the spread of carbapenem-resistant Morganella spp., Methods: This comparative genomic study included extensively drug-resistant Morganella spp isolates collected between Jan 1, 2013, and March 1, 2021, by the French National Reference Center (NRC; n=68) and European antimicrobial resistance reference centres in seven European countries (n=104), as well as one isolate from Canada, two reference strains from the Pasteur Institute collection (Paris, France), and two colistin-susceptible isolates from Bicêtre Hospital (Kremlin-Bicêtre, France). The isolates were characterised by whole-genome sequencing, antimicrobial susceptibility testing, and biochemical tests. Complete genomes from GenBank (n=103) were also included for genomic analysis, including phylogeny and determination of core genomes and resistomes. Genetic distance between different species or subspecies was performed using average nucleotide identity (ANI). Intrinsic resistance mechanisms to polymyxins were investigated by combining genetic analysis with mass spectrometry on lipid A., Findings: Distance analysis by ANI of 275 isolates identified three groups: Morganella psychrotolerans, Morganella morganii subspecies sibonii, and M morganii subspecies morganii, and a core genome maximum likelihood phylogenetic tree showed that the M morganii isolates can be separated into four subpopulations. On the basis of these findings and of phenotypic divergences between isolates, we propose a modified taxonomy for the Morganella genus including four species, Morganella psychrotolerans, Morganella sibonii, Morganella morganii, and a new species represented by a unique environmental isolate. We propose that M morganii include two subspecies: M morganii subspecies morganii (the most prevalent) and M morganii subspecies intermedius. This modified taxonomy was supported by a difference in intrinsic resistance to tetracycline and conservation of metabolic pathways such as trehalose assimilation, both only present in M sibonii. Carbapenemase producers were mostly identified among five high-risk clones of M morganii subspecies morganii. The most prevalent carbapenemase corresponded to NDM-1, followed by KPC-2, and OXA-48. A cefepime-zidebactam combination was the most potent antimicrobial against the 172 extensively drug-resistant Morganella spp isolates in our collection from different European countries, which includes metallo-β-lactamase producers. Lipid A analysis showed that the intrinsic resistance to colistin was associated with the presence of L-ARA4N on lipid A., Interpretation: This global characterisation of, to our knowledge, the widest collection of extensively drug-resistant Morganella spp highlights the need to clarify the taxonomy and decipher intrinsic resistance mechanisms, and paves the way for further genomic comparisons., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1 -carrying- P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1 -carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1 -carrying- P. stuartii and the third bla NDM-5 -carrying- P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10 , bla CMY-16 , rmtC and armA , which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Objectives: We aimed to assess the extent of integration of non-communicable disease (NCD) assessment and management in HIV clinics across Europe., Methods: A structured electronic questionnaire with 41 multiple-choice and rating-scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March-May 2023. One response per clinic was collected., Results: In all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow-up responded. Thirty-seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55-95%; and 70%, IQR: 50-88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85-100%) and metabolic disorders (90%, IQR: 75-100%) were regularly assessed, while mental health (72%, IQR: 63-85%) and pulmonary diseases (52%, IQR: 40-75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%)., Conclusion: Most HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Northern glacial refugia are a hotly debated concept. The idea that many temperate organisms survived the Last Glacial Maximum (LGM; ~26.5 to 19 thousand years) in several sites across central and northern Europe stems from phylogeographic analyses, yet direct fossil evidence has thus far been missing. Here, we present the first unequivocal proof that thermophilous trees such as oak ( Quercus ), linden ( Tilia ), and common ash ( Fraxinus excelsior ) survived the LGM in Central Europe. The persistence of the refugium was promoted by a steady influx of hydrothermal waters that locally maintained a humid and warm microclimate. We reconstructed the geological and palaeohydrological factors responsible for the emergence of hot springs during the LGM and argue that refugia of this type, allowing the long-term survival and rapid post-LGM dispersal of temperate elements, were not exceptional in the European periglacial zone.

Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT., Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m 2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m 2 on day 1, intravenous doxorubicin 50 mg/m 2 on day 1, intravenous vincristine 1·4 mg/m 2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m 2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m 2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m 2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m 2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258., Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238)., Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined., Funding: Janssen and Leukemia & Lymphoma Society., Competing Interests: Declaration of interests MD reports research grants for clinical studies from AbbVie, Bayer, Bristol-Myers Squibb/Celgene, Gilead/Kite, Janssen, and Roche; speakers' honoraria from AstraZeneca, BeiGene, Gilead/Kite, Janssen, Lilly, Novartis, and Roche; travel support from Janssen and Roche; and participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Gilead/Kite, Janssen, Lilly/Loxo Oncology, Novartis, and Roche. JDo reports payment for expert testimony (once Advisory Board) from Lilly. EG reports grants from Janssen; honoraria (educational lecture) from Genmab, Gilead, Janssen, and Lilly; support for attending meetings or travel from Janssen and Roche; and participation on a Data Safety Monitoring Board or Advisory Board for Gilead/Kite and Miltenyi Biotec. MJ reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Gilead/Kite, and Roche; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Gilead/Kite, Janssen, and Pierre Fabre. JW reports grants to his institution from GlaxoSmithKline/Novartis and Roche; honoraria for lectures from AbbVie, Amgen, Gilead, Novartis, Roche, Servier, and Takeda; participation on an Advisory Board from AbbVie, Gilead, Novartis, Roche, and Takeda. MHu reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, Celgene, Genmab, Janssen, Merck, Roche, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, AstraZeneca, Celgene, Genmab, Janssen, Merck, Roche, and Takeda. UM reports travel support from Amgen, Bristol-Myers Squibb/Celgene, Gilead, Janssen-Cilag, and Roche; Advisory Board role for Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Gilead, Incyte, Janssen-Cilag, Novartis, Pfizer, Roche, Sanofi, and Takeda; participation in national Guideline committee for the German-Swiss-Austrian Guideline for Mantle Cell Lymphoma. JR reports participation on an Advisory Board for AstraZeneca. VV reports consulting fees from AbbVie, BeiGene, Gilead, Lilly, and Roche; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Janssen; payment for expert testimony from Gilead and Roche; support for attending meetings or travel from AbbVie and Gilead. MGdS reports a research grant from AstraZeneca; payment for Advisory Boards from AbbVie, Gilead, Janssen-Cilag, Roche, and Takeda; payment or honoraria for educational events from Gilead and Janssen-Cilag; support for attending meetings or travel from AbbVie, Janssen-Cilag, Roche, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for Roche; leadership in a scientific society (Sociedade Portuguesa de Hematologia); administration board on a patient advocacy group (Associação Portuguesa Contra a Leucemia). SL reports grants or contracts to her institution from Bristol-Myers Squibb/Celgene, Genmab, HUTCHMED, Novartis, and Roche; consulting fees from AbbVie, Genmab, Gilead, Novartis, ORION Pharma, Roche, and Swedish Orphan Biovitrum (sobi); payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead, Incyte, and Novartis; participation on a Data Safety Monitoring Board or Advisory Board for Incyte. StS reports grants or contracts from any entity from AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem; consulting fees from AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem; support for attending meetings or travel from AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem; receipt of equipment, materials, drugs, medical writing, gifts, or other services from AbbVie, Acerta Pharma, Amgen, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Roche, Gilead, GlaxoSmithKline, Infinity Pharmaceuticals, Janssen, Novartis, Sunesis Pharmaceuticals, and Verastem. AK reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Bristol-Myers Squibb/Celgene, Novartis, Roche, Swedish Orphan Biovitrum (sobi), and Takeda; support for attending meetings or travel from AbbVie, BeiGene, EUSA Pharma, Swedish Orphan Biovitrum (sobi), and Takeda. RJ reports travel support for meeting attendance from BeiGene; meeting fee from Janssen. GH reports grants or contracts for clinical research from AbbVie, Gilead/Kite, Incyte, Janssen, MorphoSys, Pfizer, and Roche; consulting fees from AbbVie, ADC Therapeutics, AstraZeneca, Bristol-Myers Squibb, Genmab, Gilead/Kite, Incyte, Janssen, Lilly, Miltenyi Biotec, Novartis, and Roche; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, BeiGene, Bristol-Myers Squibb, Genmab, Gilead, Incyte, Janssen, Lilly, and Roche; support for attending meetings or travel from Gilead/Kite and Janssen; participation on a Data Safety Monitoring Board or Advisory Board for Miltenyi Biotec. CV reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, BeiGene, Bristol-Myers Squibb, Gilead/Kite, Incyte, Istituto Gentili, Janssen, Lilly, Novartis, Pfizer, Roche, and Servier; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Bristol-Myers Squibb, Incyte, Janssen, Lilly, Pfizer, and Roche. TvM reports payment or honoraria for educational lectures from Bristol-Myers Squibb/Celgene, Gilead/Kite, Janssen, and Lilly; participation on a Data Safety Monitoring Board or Advisory Board for GE HealthCare and Gilead/Kite. SW reports payment to his institution from AbbVie, Stemline Therapeutics, and Takeda; payment for expert testimony from Stemline Therapeutics; support for attending meetings or travel from AbbVie and BeiGene; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Astra Zeneca, Roche, and Stemline Therapeutics. PLZ reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, BeiGene, Bristol-Myers Squibb, Gilead, Incyte, Janssen, Kyowa Kirin, Merck Sharp and Dohme, Novartis, Roche, Swedish Orphan Biovitrum (sobi), and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, BeiGene, Bristol-Myers Squibb, Gilead, Incyte, Janssen, Kyowa Kirin, Merck Sharp and Dohme, Novartis, Roche, Swedish Orphan Biovitrum (sobi), and Takeda. UN reports consulting fees to his institution from AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Gilead, Incyte, Janssen-Cilag, Kyowa Kirin, Novartis, Pierre Fabre, Roche, and Takeda; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events to his institution from Bristol-Myers Squibb/Celgene, Gilead, Novartis, and Takeda; support for attending meetings or travel from Janssen, Gilead, Roche, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Gilead, Incyte, Janssen-Cilag, Kyowa Kirin, Novartis, Pierre Fabre, Roche, and Takeda. CH reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, Janssen, and Pfizer; support for attending meetings or travel from AbbVie and Janssen. MHa reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Falk Foundation, Gilead, Novartis, and Swedish Orphan Biovitrum (sobi); payment for expert testimony from Amgen, Bristol-Myers Squibb/Celgene, Gilead, Incyte, Janssen, Novartis, Pizer, Roche, Sanofi-Aventis, and Swedish Orphan Biovitrum (sobi). WK reports research grants provided to his institution from Amgen, Janssen, Roche, and Takeda. DG reports support for attending meetings and travel from Janssen. CS reports consulting fees from Bristol-Myers Squibb and Janssen; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca and Bristol-Myers Squibb; support for attending meetings or travel from Gilead/Kite. MU reports institutional funding of the TRIANGLE trial from Janssen. ML reports consulting fees from AstraZeneca, BeiGene, Janssen, and Lilly; honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, BeiGene, Janssen, and Lilly; participation on a Data Safety Monitoring Board with Acerta. All other authors (MT, OS, LJ, MC, LA, PH, FB, KS, JDi, CP, and EH) declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Surgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Extended aortic repair is considered a key issue for the long-term durability of surgery for DeBakey type 1 aortic dissection. The risk of aortic degeneration may be higher in young patients due to their long life expectancy. The early outcome and durability of aortic surgery in these patients were investigated in the present study., Methods: The subjects of the present analysis were patients under 60 years old who underwent surgical repair for acute DeBakey type 1 aortic dissection at 18 cardiac surgery centres across Europe between 2005 and 2021. Patients underwent ascending aortic repair or total aortic arch repair using the conventional technique or the frozen elephant trunk technique. The primary outcome was 5-year cumulative incidence of reoperation on the distal aorta., Results: Overall, 915 patients underwent surgical ascending aortic repair and 284 patients underwent surgical total aortic arch repair. The frozen elephant trunk procedure was performed in 128 patients. Among 245 propensity score-matched pairs, total aortic arch repair did not decrease the rate of distal aortic reoperation compared to ascending aortic repair (5-year cumulative incidence, 6.7% versus 6.7%, subdistributional hazard ratio 1.127, 95% c.i. 0.523 to 2.427). Total aortic arch repair increased the incidence of postoperative stroke/global brain ischaemia (25.7% versus 18.4%, P = 0.050) and dialysis (19.6% versus 12.7%, P = 0.003). Five-year mortality was comparable after ascending aortic repair and total aortic arch repair (22.8% versus 27.3%, P = 0.172)., Conclusions: In patients under 60 years old with DeBakey type 1 aortic dissection, total aortic arch replacement compared with ascending aortic repair did not reduce the incidence of distal aortic operations at 5 years. When feasible, ascending aortic repair for DeBakey type 1 aortic dissection is associated with satisfactory early and mid-term outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT04831073., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics., Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data., Design, Setting, and Participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146)., Outcome Measurements and Statistical Analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data., Results and Limitations: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent., Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data., Patient Summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid. We developed the VEGANScreener, a tool designed to assess the diet quality of vegans in Europe., Methods: Our approach combined best practices in developing diet quality metrics with scale development approaches and involved the following: (a) narrative literature synthesis, (b) evidence evaluation by an international panel of experts, and (c) translation of evidence into a diet screener. We employed a modified Delphi technique to gather opinions from an international expert panel., Results: Twenty-five experts in the fields of nutrition, epidemiology, preventive medicine, and diet assessment participated in the first round, and nineteen participated in the subsequent round. Initially, these experts provided feedback on a pool of 38 proposed items from the literature review. Consequently, 35 revised items, with 17 having multiple versions, were suggested for further consideration. In the second round, 29 items were retained, and any residual issues were addressed in the final consensus meeting. The ultimate screener draft encompassed 29 questions, with 17 focusing on foods and nutrients to promote, and 12 addressing foods and nutrients to limit. The screener contained 24 food-based and 5 nutrient-based questions., Conclusions: We elucidated the development process of the VEGANScreener, a novel diet quality screener for vegans. Future endeavors involve contrasting the VEGANScreener against benchmark diet assessment methodologies and nutritional biomarkers and testing its acceptance. Once validated, this instrument holds potential for deployment as a self-assessment application for vegans and as a preliminary dietary screening and counseling tool in healthcare settings.

During the growing season of 2021, 201 soil samples from conventionally and organically managed fields from 10 European countries and 8 cropping systems were taken, and 192 residues of synthetic pesticides were analyzed. Pesticide residues were found in 97% of the samples, and 88% of the samples contained mixtures of at least 2 substances. A maximum of 21 substances were found in conventionally managed fields, and a maximum of 12 were found in organically managed fields. The number and concentration of pesticide residues varied significantly between conventional and organic fields in 70 and 50% of the case study sites, respectively. Application records were available for a selected number of fields ( n = 82), and these records were compared to the detected substances. Residues from 52% of the applied pesticides were detected in the soils. Only 21% of the pesticide residues detected in the soil samples were applied during the 2021 growing season. From the application data, predicted environmental concentrations of residues in soil were calculated and compared to the measured concentrations. These estimates turned out not to be accurate. The results of this study show that most European agricultural soils contain mixtures of pesticide residues and that current calculation methods may not reliably estimate their presence.

Humans impact terrestrial, marine and freshwater ecosystems, yet many broad-scale studies have found no systematic, negative biodiversity changes (for example, decreasing abundance or taxon richness). Here we show that mixed biodiversity responses may arise because community metrics show variable responses to anthropogenic impacts across broad spatial scales. We first quantified temporal trends in anthropogenic impacts for 1,365 riverine invertebrate communities from 23 European countries, based on similarity to least-impacted reference communities. Reference comparisons provide necessary, but often missing, baselines for evaluating whether communities are negatively impacted or have improved (less or more similar, respectively). We then determined whether changing impacts were consistently reflected in metrics of community abundance, taxon richness, evenness and composition. Invertebrate communities improved, that is, became more similar to reference conditions, from 1992 until the 2010s, after which improvements plateaued. Improvements were generally reflected by higher taxon richness, providing evidence that certain community metrics can broadly indicate anthropogenic impacts. However, richness responses were highly variable among sites, and we found no consistent responses in community abundance, evenness or composition. These findings suggest that, without sufficient data and careful metric selection, many common community metrics cannot reliably reflect anthropogenic impacts, helping explain the prevalence of mixed biodiversity trends., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

To enhance our understanding of forest carbon sequestration, climate change mitigation and drought impact on forest ecosystems, the availability of high-resolution annual forest growth maps based on tree-ring width (TRW) would provide a significant advancement to the field. Site-specific characteristics, which can be approximated by high-resolution Earth observation by satellites (EOS), emerge as crucial drivers of forest growth, influencing how climate translates into tree growth. EOS provides information on surface reflectance related to forest characteristics and thus can potentially improve the accuracy of forest growth models based on TRW. Through the modelling of TRW using EOS, climate and topography data, we showed that species-specific models can explain up to 52 % of model variance (Quercus petraea), while combining different species results in relatively poor model performance (R 2  = 13 %). The integration of EOS into models based solely on climate and elevation data improved the explained variance by 6 % on average. Leveraging these insights, we successfully generated a map of annual TRW for the year 2021. We employed the area of applicability (AOA) approach to delineate the range in which our models are deemed valid. The calculated AOA for the established forest-type models was 73 % of the study region, indicating robust spatial applicability. Notably, unreliable predictions predominantly occurred in the climate margins of our dataset. In conclusion, our large-scale assessment underscores the efficacy of combining climate, EOS and topographic data to develop robust models for mapping annual TRW. This research not only fills a critical void in the current understanding of forest growth dynamics but also highlights the potential of integrated data sources for comprehensive ecosystem assessments., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Canopy accession strategies reveal much about tree life histories and forest stand dynamics. However, the protracted nature of ascending to the canopy makes direct observation challenging. We use a reconstructive approach based on an extensive tree ring database to study the variability of canopy accession patterns of dominant tree species (Abies alba, Acer pseudoplatanus, Fagus sylvatica, Picea abies) in temperate mountain forests of Europe and elucidate how disturbance histories, climate, and topography affect canopy accession. All four species exhibited high variability of radial growth histories leading to canopy accession and indicated varying levels of shade tolerance. Individuals of all four species survived at least 100 years of initial suppression. Fir and particularly beech, however, survived longer periods of initial suppression, exhibited more release events, and reached the canopy later on average, with a larger share of trees accessing the canopy after initially suppressed growth. These results indicate the superior shade tolerance of beech and fir compared to spruce and maple. The two less shade-tolerant species conversely relied on faster growth rates, revealing their competitive advantage in non-suppressed conditions. Additionally, spruce from higher-elevation spruce-dominated forests survived shorter periods of initial shading and exhibited fewer releases, with a larger share of trees reaching the canopy after open canopy recruitment (i.e. in absence of suppression) and no subsequent releases compared to spruce growing in lower-elevation mixed forests. Finally, disturbance factors were identified as the primary driver of canopy accession, whereby disturbances accelerate canopy accession and consequently regulate competitive interactions. Intensifying disturbance regimes could thus promote shifts in species composition, particularly in favour of faster-growing, more light-demanding species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe., Methods: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022., Results: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries., Conclusions: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors., Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita)., Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01)., Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study., Competing Interests: LH, PP, EP, EN received consultancy fees from IBSA Biochimique SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PM declared a shared affiliation with the author TB to the handling editor at the time of review., (Copyright © 2023 Žarković, Attanasio, Nagy, Negro, Papini, Perros, Cohen, Akarsu, Alevizaki, Ayvaz, Bednarczuk, Berta, Bodor, Borissova, Boyanov, Buffet, Burlacu, Ćirić, Díez, Dobnig, Fadeyev, Field, Fliers, Frølich, Führer, Galofré, Hakala, Jiskra, Kopp, Krebs, Kršek, Kužma, Lantz, Lazúrová, Leenhardt, Luchytskiy, McGowan, Melo, Metso, Moran, Morgunova, Mykola, Beleslin, Niculescu, Perić, Planck, Poiana, Puga, Robenshtok, Rosselet, Ruchala, Riis, Shepelkevich, Unuane, Vardarli, Visser, Vrionidou, Younes, Yurenya and Hegedüs.)

Owing to a long history of anthropogenic pressures, freshwater ecosystems are among the most vulnerable to biodiversity loss 1 . Mitigation measures, including wastewater treatment and hydromorphological restoration, have aimed to improve environmental quality and foster the recovery of freshwater biodiversity 2 . Here, using 1,816 time series of freshwater invertebrate communities collected across 22 European countries between 1968 and 2020, we quantified temporal trends in taxonomic and functional diversity and their responses to environmental pressures and gradients. We observed overall increases in taxon richness (0.73% per year), functional richness (2.4% per year) and abundance (1.17% per year). However, these increases primarily occurred before the 2010s, and have since plateaued. Freshwater communities downstream of dams, urban areas and cropland were less likely to experience recovery. Communities at sites with faster rates of warming had fewer gains in taxon richness, functional richness and abundance. Although biodiversity gains in the 1990s and 2000s probably reflect the effectiveness of water-quality improvements and restoration projects, the decelerating trajectory in the 2010s suggests that the current measures offer diminishing returns. Given new and persistent pressures on freshwater ecosystems, including emerging pollutants, climate change and the spread of invasive species, we call for additional mitigation to revive the recovery of freshwater biodiversity., (© 2023. The Author(s).)

Background: The appearance of Slavs in East-Central Europe has been the subject of an over 200-year debate driven by two conflicting hypotheses. The first assumes that Slavs came to the territory of contemporary Poland no earlier than the sixth century CE; the second postulates that they already inhabited this region in the Iron Age (IA). Testing either hypothesis is not trivial given that cremation of the dead was the prevailing custom in Central Europe from the late Bronze Age until the Middle Ages (MA)., Results: To address this problem, we determined the genetic makeup of representatives of the IA Wielbark- and MA Slav-associated cultures from the territory of present-day Poland. The study involved 474 individuals buried in 27 cemeteries. For 197 of them, genome-wide data were obtained. We found close genetic affinities between the IA Wielbark culture-associated individuals and contemporary to them and older northern European populations. Further, we observed that the IA individuals had genetic components which were indispensable to model the MA population., Conclusions: The collected data suggest that the Wielbark culture-associated IA population was formed by immigrants from the north who entered the region of contemporary Poland most likely at the beginning of the first millennium CE and mixed with autochthons. The presented results are in line with the hypothesis that assumes the genetic continuation between IA and MA periods in East-Central Europe., (© 2023. The Author(s).)

Background and Aims: Southwestern Asia is a significant centre of biodiversity and a cradle of diversification for many plant groups, especially xerophytic elements. In contrast, little is known about the evolution and diversification of its hygrophytic flora. To fill this gap, we focus on Cardamine (Brassicaceae) species that grow in wetlands over a wide altitudinal range. We aimed to elucidate their evolution, assess the extent of presumed historical gene flow between species, and draw inferences about intraspecific structure., Methods: We applied the phylogenomic Hyb-Seq approach, ecological niche analyses and multivariate morphometrics to a total of 85 Cardamine populations from the target region of Anatolia-Caucasus, usually treated as four to six species, and supplemented them with close relatives from Europe., Key Results: Five diploids are recognized in the focus area, three of which occur in regions adjacent to the Black and/or Caspian Sea (C. penzesii, C. tenera, C. lazica), one species widely distributed from the Caucasus to Lebanon and Iran (C. uliginosa), and one western Anatolian entity (provisionally C. cf. uliginosa). Phylogenomic data suggest recent speciation during the Pleistocene, likely driven by both geographic separation (allopatry) and ecological divergence. With the exception of a single hybrid (allotetraploid) speciation event proven for C. wiedemanniana, an endemic of southern Turkey, no significant traces of past or present interspecific gene flow were observed. Genetic variation within the studied species is spatially structured, suggesting reduced gene flow due to geographic and ecological barriers, but also glacial survival in different refugia., Conclusions: This study highlights the importance of the refugial regions of the Black and Caspian Seas for both harbouring and generating hygrophytic species diversity in Southwestern Asia. It also supports the significance of evolutionary links between Anatolia and the Balkan Peninsula. Reticulation and polyploidization played a minor evolutionary role here in contrast to the European relatives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anaplastic thyroid carcinoma (ATC) is a rare cancer accounting for 40% of thyroid cancer-specific deaths. In the last 5 years, improved insights into molecular pathways led the Food and Drug Administration to license BRAF/MEK inhibitors (B/Mi) in BRAF V600E -mutant ATC, and pembrolizumab in solid cancer with high tumour mutational burden (TMB-H) (≥10 mutations/megabase) (mut/Mb). In Europe, clinicians face challenges in prescribing novel treatments, as the European Medical Association (EMA) has not licensed B/Mi nor immunotherapy (IO) for ATC so far. Some patients manage to receive these drugs through alternative ways. We investigated the extent of this phenomenon launching an online survey from March 12th to 19th 2021 open to 239 Institutions in the EORTC Endocrine and Head & Neck Cancer Groups. Questions enquired about the number of ATC patients evaluated/year, feasibility of BRAF assessment, accessibility to B/Mi-IO, availability of clinical trials and interest in new studies. Colleagues from 94 Institutions (20 Countries) joined: 30 centres evaluated ≥5 ATC patients/year, with an overall incidence >200 patients/year. 80.8% tested BRAF status, 43.6% by next-generation sequencing. 62.7% and 70% of responders reported limitations in prescribing B/Mi and IO, respectively: either the impossibility of offering them, or drugs accessibility exclusively under certain conditions (e.g. health insurance, clinical trials, compassionate use, off-label). Only 13.8% had clinical trials ongoing while 91.5% of sites claimed ATC-dedicated trials. Disparities in access to novel treatments are diffuse. Access to cutting-edge therapies is an urgent issue in this setting, and clinical trials seem feasible within an appropriate network., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.D.L. received conference honoraria/Advisory Board from EISAI, MSD, Merck Serono, Eli Lilly, Sanofi, Sunpharma, IPSEN, Bayer, Roche, Gentili SrL, New Bridge and has been consultant for Eisai. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic has not only impacted intensive care units, but all healthcare services generally. This PsyGipo2C project specifically investigates how psychiatry and mental health professionals have been affected by the reorganizations and constraints imposed, which have reshaped their often already difficult working conditions., Methods: Our research combined quantitative and qualitative methods, surveying and interviewing health professionals of all occupations working in psychiatric and mental health services. A questionnaire was completed by 1241 professionals from 10 European countries, and 13 group interviews were conducted across 5 countries. In addition to this, 31 individual interviews were conducted in Belgium and France., Results: Among the questionnaire respondents, 70.2% felt that their workload had increased, particularly due to their tasks being diversified and due to increased complexity in the provision of care. 48.9% felt that finding a work-life balance had become more difficult, and 59.5% felt their health had been affected by the crisis. The impact of the health crisis nevertheless varied across professions: our data provides insight into how the health measures have had a differential impact on professional tasks and roles across the various categories of occupations, obliging professionals to make various adaptations. The distress incurred has been linked not only to these new constraints in their work, but also to the combination of these with other pressures in their personal lives, which has consequently compromised their well-being and their ability to cope with multiple demands., Discussion: The COVID-19 health crisis has had varying impacts depending on the profession and access to remote work, sometimes leading to conflicts within the teams. The suffering expressed by the professionals was tied to their values and patterns of investment in work. Our research also highlights how these professionals made little use of the psychological supports offered, probably due to a reluctance to acknowledge that their mental health was affected., (© 2022. The Author(s).)

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Martins dos Santos V et al.)

Background: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear., Methods: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause., Results: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04)., Conclusions: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.)., (Copyright © 2022 Massachusetts Medical Society.)

Viscum album L. is a plant of great importance due to its influence on the host trees and, by extension, entire ecosystems. The species is also significant to humans-on the one hand, because of its use in medicine, and on the other, because of the growing threat it poses to the stability of conifer stands. Therefore, it is important to recognize the future range of three mistletoe subspecies (Viscum album subsp. album, V. album subsp. austriacum, and V. album subsp. abietis). Modelling of the potential range of these subspecies was performed using MAXENT software. Locations were collected from literature and databases. A total number of 3335 stands were used. Bioclimatic data for the current conditions and three future scenarios (SSP 1.26, SSP 3.70, SSP 5.85) were downloaded from the CHELSA database. The results confirmed that the temperature is the key variable on the potential range of the analysed subspecies. V. album subsp. abietis is withdrawing from its range according to all scenarios. In the case of V. album subsp. austriacum, a slight range shift is visible. Only the V. album subsp. album will expand non-directionally. The reason is most likely a very large number of host species and greater genetic variability compared to the subspecies found on conifers., (© 2022. The Author(s).)

The Eurasian beaver is currently found in at least 32 European countries, with many of these populations being established in the 1960s. In most European countries, the beaver is under protection, however, when the population is strong, the beaver becomes a game species. In Poland, the beaver is partially protected despite the species having a strong population. In this study we aimed to compare the development trends of Eurasian beaver populations in two management regimes, in Poland (protected) and Belarus (hunted), between 2004 and 2019. We compared beaver population trends in both countries, and analyzed the factors that could impact population growth. In Poland, during this period the population increased 3.5 times, while in Belarus it was only 20%. Distinct differences in the rate of population numbers increase were also observed between regions in Poland, but a stable, slight increase similar in all regions in Belarus. Our study did not show that precipitation or the density of this species influenced the rate of population development in Poland. During this period, hunting and wolf density significantly and negatively impacted beaver population growth in Belarus, but in the long-term analysis, hunting had a lower impact on beaver population growth. We concluded that we can expect a further increase in this population in Poland. Long-term hunting at a level of 13,7% (based on the analysis of population dynamics and hunting bags for Belarus) of the annual population seems to be a safe value for the beaver population. Nevertheless more detailed analysis should be carried out in the face of the large differences between regions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The European Society of Gastrointestinal Endoscopy (ESGE) presents a short list of performance measures for colonoscopy in inflammatory bowel disease (IBD) patients. Current performance measures for colonoscopy mainly focus on detecting (pre)malignant lesions. However, these performance measures are not relevant for all colonoscopy indications in IBD patients. Therefore, our aim was to provide endoscopy services across Europe and other interested countries with a tool for quality monitoring and improvement in IBD colonoscopy. Eight key performance measures and one minor performance measure were recommended for measurement and evaluation in daily endoscopy practice., Competing Interests: R. Bisschops has received research grants and speaker’s fees from Fujifilm, Norgine, and Pentax; he has provided consultancy for Fujifilm, Norgine, and Pentax. E. Dekker has received a research grant and has endoscopic equipment on loan from Fujifilm; she has received speakerʼs fees from Olympus, GI Supply, Norgine, Ipsen, Paion, and Fujifilm; she has provided consultancy for Fujifilm, Olympus, GI Supply, Paion, and Ambu. J.E. East has received speaker’s fees from Falk and Jenssen, has served on clinical advisory boards for Paion, and has served on the clinical advisory board and has share options in Satisfai Health. M. Iacucci has received research grants from Olympus, Pentax, and Fujifilm. M.F. Kaminski has equipment on loan from Fujifilm; he has received speaker’s fees from Boston Scientific, Ipsen, and Recordati, and a research grant from Olympus; he has provided consultancy for Olympus and ERBE. J.G. Karstensen has received speaker’s fees from Norgine and provided for consultancy from Ambu and SNIPR Biome. M. Keuchel has received speaker’s fees from Medtronic and Olympus, and study support from AnXRobotics; he has provided consultancy for Medtronic. M. Pellisé has provided consultancy to Norgine Iberia, GI Supply, and Fujifilm; she has served on the editorial board of Thieme, has been the ESGE equity and diversity working group chair and a councillor for SEED, and is president elect of AEG; her department has received research support from Fujifilm and Casen Recordat. L. Peyrin-Biroulet has received personal fees from Abbvie, Janssen, Takeda, and Celltrion. None of the above conflicts of interest are of relevance to this manuscript. M. Bugajski, C. Carretero, G. Cortas, E.J. Despott, M. Löwenberg, A. Monged, A. Murino, K.J. Nass, O.M. Nardone, H. Neumann, M. Omar, and M.D. Rutter declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data., Methods: We analysed 2015-2020 MASK-air ® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms ('VAS Global Symptoms') and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year., Results: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p < .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H 1 -antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more., Conclusions: Allergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies., Methods: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021., Results: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables., Conclusions: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond., (© 2022. The Author(s).)

Objective: The Parliamentary Assembly invited the member states of the Council of Europe to 'guarantee women's effective exercise of their right of access to a safe and legal abortion'. While abortion legislation and statistics give an impression of the legislative, cultural, and religious views of the societies and the socio-economic health of the female population, only one study conducted in 2011 looked into the current legislation and trends in terminations of pregnancy in the European Union. Materials and Methods: From January 2017 to December 2018, a group of experts, the authors of the present article, liaised with colleagues practising in 32 European countries to collect data on abortion legislation and statistics using three different questionnaires. Results: The article presents the results of this initiative and compares the status quo and recent trends in abortion legislation and statistics across Europe. Conclusions: The European legislations are still very heterogenous and abortion rates vary widely between countries, confirming that laws do not correlate with abortion rates. This compilation of data, also available on a website (www.abort-report.eu), may help to change laws to better meet the needs of women who decided to have an abortion as a solution to the underlying problem of an unwanted pregnancy.

Since time immemorial, bodies of deceased have been an integral part of teaching anatomy, and therefore the study of medicine. Without them, the teaching of anatomy, clinical anatomy and many research projects could not be realized. Nowadays, the European countries allow to use exclusively bodies of the deceased donors. Recently, we have registered a growing trend in the needs of the bodies not only for the purposes of medical education, but also for those of clinical anatomy. The question also arose of the suitability of using COVID-19 positive donors or the legislative possibility of obtaining bodies in the absence of donors in the donor program. Our communication addresses current issues of body donation for teaching and research purposes and their use in the Czech Republic.

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species., (© 2021 John Wiley & Sons Ltd.)

BACKGROUND The supplementary treatment of burns with enzymatic debridement with Nexobrid® was approved in Europe in 2013. The 2017 European consensus guidelines on the removal of eschar in burns by bromelain-based enzymatic debridement were updated in 2020. This questionnaire-based study aimed to obtain a consensus from 5 Polish burns centers on eschar removal by Nexobrid® in burns following the 2020 updated European consensus guidelines. MATERIAL AND METHODS A panel of 5 experts representing the leading burn treatment centers in Poland (Cracow, Gryfice, Siemanowice Śląskie, Poznań, and Łęczna) was convened. A modified Delphi process was implemented with panel member selection, literature review, 2 rounds of voting in which panelists were asked to evaluate the European consensus and Polish consensus building by data analysis, statements preparation, final voting, and manuscript drafting. RESULTS The knowledge and experience of experts from Poland's leading burn centers resulted in the development of guidelines, formulated as 24 statements representing the following areas: indications and usage, pain management, application principles, post-enzymatic debridement wound dressing, and early and long-term outcomes. An analysis of the 7-point Likert scale polls revealed that 23 of the 24 statements achieved 100% consensus. CONCLUSIONS The findings from this survey from 5 major centers in Poland supported the main recommendations from the 2020 updated European consensus guidelines on the removal of eschar in burns by Nexobrid® and may serve as a practical guide for surgeons who care for patients with burns in this country.

The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland.

Introduction: unCoVer-Unravelling data for rapid evidence-based response to COVID-19-is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic., Methods and Analysis: From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients' baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded., Ethics and Dissemination: After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer's activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF <35% (HR 4.71, 95%CI 1.90 to 11.66) to CV death. Repeated PCI on ULMCA occurred in 91 (28%) patients during the course of follow up and did not significantly impact on freedom from all-cause or CV mortality. In conclusion, in a large, unselected population treated with PCI on ULMCA, 47% died after 15 years, 17% due to CV causes. Age, number of vessels treated during index PCI and depressed LVEF increased risk of all cause death, while re-PCI on ULMCA did not impact survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Domestication of horses fundamentally transformed long-range mobility and warfare 1 . However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling 2-4 at Botai, Central Asia around 3500 BC 3 . Other longstanding candidate regions for horse domestication, such as Iberia 5 and Anatolia 6 , have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association 7 between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC 8,9 driving the spread of Indo-European languages 10 . This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture 11,12 ., (© 2021. The Author(s).)

Background: Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma., Methods and Findings: We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer-in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations., Conclusions: We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DM reports grants, personal fees and non-financial support from GlaxoSmithKline, grants and personal fees from NeuroTrauma Sciences, personal fees from Pfizer Ltd, personal fees from PressuraNeuro, grants and personal fees from Lantmannen AB, grants and personal fees from Integra, outside the submitted work;DM is an Academic Editor on PLOS Medicine’s editorial board. AM reports grants from European Union Framework 7, grants from Integra Life Sciences, grants from Hannelore Kohl Stiftung, grants from Neurotrauma Sciences, grants from BioDirection, during the conduct of the study; personal fees from PressuraNeuro, personal fees from Integra LifeSciences, personal fees from NeuroTrauma Sciences, outside the submitted work;. F L reports grants from EU Framework 7, during the conduct of the study; grants from Trauma Audit and Research Network, outside the submitted work; there are no other relationships or activities that could appear to have influenced the submitted work. There are no other author competing interests.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis., Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements., Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable., Conclusions and Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD., (© 2021 John Wiley & Sons Ltd.)

Reproductive longevity is essential for fertility and influences healthy ageing in women 1,2 , but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations 3 . The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)