Search

Aim: Asymptomatic atrial fibrillation (AF) is frequent and associated with disease progression. This meta-analysis aimed to estimate the prevalence of asymptomatic AF and identify risk factors associated with asymptomatic status., Methods: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until January 8, 2025. Double-independent study selection, data extraction and quality assessments were performed. Random-effects meta-analysis was used. Estimates are presented with the asymptomatic individuals in the nominator and the symptomatic patients in the denominator. The assessment of the prevalence of asymptomatic AF and the identification of risk factors associated with the asymptomatic status comprised the main endpoints., Results: Thirty-seven studies (224273 participants) were included. The prevalence of asymptomatic AF was 27% (95% confidence interval {CI}=[22%,33%]; I2=100%). Risk factors positively associated with the asymptomatic status were male sex (odds ratio {OR}=1.67, 95%CI=[1.48,1.89], p<0.001, I2=85%), diabetes mellitus (OR=1.19, 95%CI=[1.07,1.33], p=0.002, I2=87%), chronic kidney disease (OR=1.21, 95%CI=[1.08,1.36], p<0.001, I2=80%) and stroke/transient ischemic attack (OR=1.43, 95%CI=[1.18,1.73], p<0.001, I2=95%), while heart failure was negatively associated with asymptomatic AF (OR=0.71, 95%CI=[0.54,0.94], p=0.017, I2=97%). Asymptomatic status was also positively associated with permanent AF (OR=2.13, 95%CI=[1.28,3.55]; p=0.004; I2=98%) and negatively associated with catheter ablation (OR=0.63, 95%CI=[0.44,0.91]; p=0.012; I2=95%), beta-blockers (OR=0.90, 95%CI=[0.82,0.98]; p=0.018; I2=68%) and antiarrhythmics (OR=0.53, 95%CI=[0.35,0.79]; p=0.002; I2=95%)., Conclusions: Asymptomatic AF was estimated around 27%, with large variability depending on the prevalence of risk factors associated with asymptomatic status. Asymptomatic individuals had distinct characteristics compared to symptomatic patients, regardless of symptoms' assessment methods and rhythm/rate control interventions. Our results could inform AF screening practices to target asymptomatic individuals., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Postoperative outcomes of patients with normotensive pheochromocytomas are poorly documented. We aimed to evaluate the impact of preoperative hypertension on post-operative outcomes following adrenalectomy for pheochromocytoma., Methods: An international retrospective study of patients undergoing adrenalectomy for pheochromocytoma in 46 centers between 2012-2022 was performed. Hypertensive and normotensive pheochromocytoma were defined respectively by the presence or absence of hypertension history before or at the time of pheochromocytoma diagnosis. To evaluate differences in postoperative outcomes between hypertensive and normotensive patients, propensity score matched (PSM) analysis was performed., Results: Among 2,016 patients with pheochromocytoma, 1,034 (51.2%) had preoperative hypertension and 982 (49.8%) were normotensive. Hypertensive patients were 4.5 years older (p<0.001), had higher prevalence of type 2 diabetes (p<0.001), had a higher median Charlson Comorbidity Index (2.0 vs. 1.0; p<0.001) and had an ASA III-IV more frequently (41% vs. 19.9%, p<0.001) than normotensive patients. Non-adjusted analysis demonstrated that hypertensive patients had longer operative time (115.0 vs. 103.5 minutes; p=0.026), higher rate of vasopressors at skin closure (19.7% vs 15.4%; p=0.013), more perioperative blood transfusions (7.7% vs. 5.0%; p=0.016) and increased complication rate (21.6% vs. 17.7%; p=0.029). However, after 1:1 PSM, we found that readmission, complications, and serious complications were similar between cohorts., Conclusions: Patients with hypertensive pheochromocytomas have a higher risk of postoperative complications than normotensive cases due to the association of hypertension with a higher burden of comorbidities and older age. However, hypertension is not an independent risk factor of postoperative complications after pheochromocytoma surgery., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Surrogacy is the assisted reproductive technology (ART) practice in which a person becomes pregnant, carries, and delivers a child on behalf of another couple/person, who are the intended parent(s). Surrogacy is an especially complex practice as the interests of the intended parents, the gestational carrier, and the future child may differ. This paper considers ethical questions related to different forms of surrogacy. It concludes that non-commercial surrogacy is an acceptable method of assisted reproduction for specific indications. When using surrogacy to form a family, it is essential that there are measures to protect all parties, to guarantee well-considered decision-making, and to minimize risks. The current paper formulates recommendations to promote these measures. This paper is an update to the ESHRE Task Force Ethics and Law Paper 10: Surrogacy and replaces this paper., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Storm Daniel, characterized as the most severe 21st century flood event in Greece, struck the Regions of Thessaly and Central Greece in early September 2023, resulting in 17 reported direct fatalities., Methods: This study evaluated all-cause excess mortality in the prefectures of Fthiotida, Karditsa/Trikala and Magnesia affected by Storm Daniel. We compared weekly deaths during the first week and the 90 days following the flood, to expected deaths based on historical trends 2015-2019., Results: During the week of the flooding event, Fthiotida, Karditsa/Trikala and Magnesia prefectures experienced mortality increases of 57% (95%CI: 19%-95%), 40% (95%CI: 13%-66%) and 39% (95%CI: 7%-70%) over expected levels, respectively. A total of 54 (95% CI: 31-77) excess deaths were recorded during the week of Storm Daniel's landfall, with the cumulative number of excess deaths reaching to 335 (95% CI: 250-420) over subsequent 90 days., Conclusion: Conventional approaches that focus solely on immediate and direct flood fatalities underestimate the overall and actual health risks faced by flood-affected communities. Floods have complex and long-term health effects, necessitating continuous monitoring of the affected communities., (© The Author(s) 2025. Published by Oxford University Press on behalf of Faculty of Public Health.)

Introduction: The evolving landscape of general practice (GP)/family medicine (FM) in the post-COVID-19 era, focussing on integrating telemedicine and remote consultations requires a new definition for this specialty. Hence, a broader consensus-based definition of post-COVID-19 GP/FM is warranted., Methods: This study involved a modified electronic Delphi technique involving 27 specialists working in primary care recruited via convenient and snowball sampling. The Delphi survey was conducted online between August 2022 and April 2023, utilizing the Google Forms platform. Descriptive statistics were employed to analyse consensus across Delphi rounds., Results: Twenty-six international experts participated in the survey. The retention rate through the second and third Delphi rounds was 96.2% (n = 25). The broader consensus definition emphasizes person-centred care, collaborative patient-physician partnerships, and a holistic approach to health, including managing acute and chronic conditions through in-person or remote access based on patient preferences, medical needs, and local health system organization., Conclusion: The study highlights the importance of continuity of care, prevention, and coordination with other healthcare professionals as core values of primary care. It also reflects the role of GP/FM in addressing new challenges post-pandemic, such as healthcare delivery beyond standard face-to-face care (e.g. remote consultations) and an increasingly important role in the prevention of infectious diseases. This underscores the need for ongoing research and patient involvement to continually refine and improve primary healthcare delivery in response to changing healthcare landscapes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To investigate whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19+CD21-CD11c+T-bet+) and double-negative B cells/DN (CD19+IgD-CD27- CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans., Methods: Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients. Whole blood assay cultures, combined with in vitro pharmacological treatments, were performed to evaluate the effects of hydroxychloroquine, anifrolumab and fasudil (a ROCK kinase inhibitor) on T-bet+ B cells' percentage. Moreover, previously published single-cell RNA sequencing (scRNA-seq) data were used in a meta-analysis to allow characterization of genes and pathways associated with the biology of T-bet in B cells., Results: T-bet+ B cells displayed an expansion in SLE patients [1.47 (1.9 - 0.7) vs 10.85 (37.4 - 3.6)]. Similarly, both ABCs and DN were found to be expanded. Interestingly, percentages of T-bet+ B cells positively correlated with patients' SLEDAI scores (rs=0.55, p=0.007). Cell culture experiments conducted, revealed that all three agents tested can deplete T-bet+ B cells (without affecting the cell viability of lymphocytes, T cells and B cells). According to bioinformatics analyses, T-bet is highly expressed in two B cell clusters with pathogenic characteristics for SLE (designated as atypical memory B cells and activated naïve B cells). These clusters can be targeted for therapeutic interventions., Conclusions: T-bet+ B cells can serve as a putative prognostic biomarker of lupus severity. Circumstantial data suggest that these cells may promote disease pathogenesis and may represent a novel therapeutic target., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology.)

Haemodialysis (HD) is a life-saving therapy for individuals with kidney failure. Post-filter haemodiafiltration (HDF) and high-flux HD are the most widely used treatment modalities. To date, five randomised controlled trials (RCTs) have been performed that compare all-cause and cardiovascular (CV) mortality between HDF and low- or high-flux HD in adults receiving maintenance dialysis for at least one year. RCTs, meta-analyses and pooled individual patient data analyses have been published on this topic. However, all of them are limited by the heterogeneity of inclusion criteria and significant methodological shortcomings, including informative selection bias and the exclusion of poorly performing patients from the HDF arm after randomisation. Given this background, the European Dialysis Working Group of the European Renal Association presents a Consensus Statement on HDF and high-flux HD, addressing three key outcomes: survival, health-related quality of life and biochemical endpoints. A separate section is dedicated to paediatric patients. We searched five large electronic databases to identify parallel or cross-over RCTs comparing HDF with high-flux HD on pre-defined outcome measures. Using a mini-Delphi method, we developed twenty-two key consensus points by combining meta-analyses, clinical experience and expert opinion. They aim to inform and assist in decision-making and are not intended to define a standard of care. The key summary point is that HDF appears to be associated with improved overall and CV survival, provided high convection volumes are achieved. The generalizability of these findings to the entire dialysis population depends on the patient's overall health and requires further study., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Background: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes., Methods: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200-≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR >60 or <60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety., Results: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium-glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline., Conclusions: FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Motivation: Identifying antibody binding sites, is crucial for developing vaccines and therapeutic antibodies, processes that are time-consuming and costly. Accurate prediction of the paratope's binding site can speed up the development by improving our understanding of antibody-antigen interactions., Results: We present ParaSurf, a deep learning model that significantly enhances paratope prediction by incorporating both surface geometric and non-geometric factors. Trained and tested on three prominent antibody-antigen benchmarks, ParaSurf achieves state-of-the-art results across nearly all metrics. Unlike models restricted to the variable region, ParaSurf demonstrates the ability to accurately predict binding scores across the entire Fab region of the antibody. Additionally, we conducted an extensive analysis using the largest of the three datasets employed, focusing on three key components: (i) a detailed evaluation of paratope prediction for each complementarity-determining region loop, (ii) the performance of models trained exclusively on the heavy chain, and (iii) the results of training models solely on the light chain without incorporating data from the heavy chain., Availability and Implementation: Source code for ParaSurf, along with the datasets used, preprocessing pipeline, and trained model weights, are freely available at https://github.com/aggelos-michael-papadopoulos/ParaSurf., (© The Author(s) 2025. Published by Oxford University Press.)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guideline for Identification and Management of Chronic Kidney Disease (CKD) is a welcome development, coming 12 years after the paradigm-changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists, now being proven in multiple randomized controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD Guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and the fact that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such, the KDIGO 2024 CKD Guideline should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Sex chromosomes differ in their inheritance properties from autosomes and hence may encode complementary information about past demographic events. We compiled and analyzed a range-wide resequencing data set of the red deer (Cervus elaphus), one of the few Eurasian herbivores of the Late Pleistocene megafauna still found throughout much of its historic range. Our analyses of 144 whole genomes reveal striking discrepancies between the population clusters suggested by autosomal and X-chromosomal data. We postulate that the genetic legacy of Late Glacial population structure is better captured and preserved by the X chromosome than by autosomes, for two reasons. First, X chromosomes have a lower Ne and hence lose genetic variation faster during isolation in glacial refugia, causing increased population differentiation. Second, following postglacial recolonization and secondary contact, immigrant males pass on their X chromosomes to female offspring only, which effectively halves the migration rate when gene flow is male mediated. Our study illustrates how a comparison between autosomal and sex chromosomal phylogeographic signals unravels past demographic processes that otherwise would remain hidden., Competing Interests: Conflict of Interest: The authors declare no conflicts of interest., (© The Author(s) 2025. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Study Question: Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART?, Summary Answer: Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator., What Is Known Already: All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth. A meta-analysis published in 2021 suggested that biosimilars of follitropin alfa are associated with lower live birth rates compared to the originator. Since then, more relevant RCTs have been published, and thus an updated critical synthesis of the available evidence is urgently warranted., Study Design, Size, Duration: A systematic review and meta-analysis were performed to compare biosimilars versus the originator of follitropin alfa in women undergoing ovarian stimulation for ART. A literature search was conducted until January 2024 in MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, WHO, Clinicaltrials.gov, and others to identify eligible RCTs. The primary outcome was live birth. Secondary outcomes included clinical and ongoing pregnancy, duration of gonadotrophin administration and total FSH dose, number of oocytes retrieved, and ovarian hyperstimulation syndrome (OHSS)., Participants/materials, Setting, Methods: Data were extracted independently by two reviewers. Quality was assessed using the RoB-2 Tool by Cochrane, and a sensitivity analysis was performed by excluding studies having high risk of bias. Meta-analysis was performed using the random or fixed effects model depending on the presence or not of significant (>50%) statistical heterogeneity (I2). Results were combined using the intention-to-treat principle and are reported as risk ratio (RR) or weighted-mean-difference (WMD) with 95% CIs., Main Results and the Role of Chance: Eight RCTs (n = 2987) (published between 2015 and 2023) were identified, assessing seven biosimilar products of follitropin alfa. The number of patients included in the eligible studies ranged from 100 to 1100. Three of the RCTs were deemed to be at high risk of bias. The duration of gonadotrophin administration was shorter in the biosimilars group (WMD: -0.19 days, 95% CI: -0.34 to -0.05; I2 = 0%, 5 studies, n = 2081), while no difference was observed in the total dose of FSH (WMD: -34.69 IUs, 95% CI: -74.54 to 5.16; I2 = 15.53%, 5 studies, n = 2081). No difference was observed in the number of oocytes retrieved (WMD: 0.27, 95% CI: -0.43 to 0.96; I2 = 10.7%, 6 studies, n = 1527) and OHSS rates (RR: 1.17, 95% CI: 0.90-1.52; I2 = 0%, 8 studies, n = 2986) between the two groups. A significantly lower live birth rate was observed using the biosimilars of follitropin alfa compared to the originator in women undergoing ovarian stimulation for ART (RR: 0.83, 95% CI: 0.72-0.96; I2 = 0%, 6 studies, n = 2335; moderate certainty of evidence). Similarly, clinical pregnancy (RR: 0.82, 95% CI: 0.73-0.92; I2 = 0%, 7 studies, n = 2876; low certainty of evidence) and ongoing pregnancy rates (RR: 0.81, 95% CI: 0.70-0.94; I2 = 0%, 7 studies, n = 1886; low certainty of evidence) were lower in the biosimilars group. These results were not materially altered in the sensitivity analyses performed where studies deemed at high risk of bias were excluded., Limitations, Reasons for Caution: This meta-analysis included RCTs evaluating seven different biosimilars of follitropin alfa; however, pooled data appeared to be homogeneous. No data were available comparing biosimilars of follitropin alfa with the originator regarding cumulative live birth rate per aspiration or the probability of live birth in frozen thawed cycles. The population examined in the eligible RCTs includes mainly normal responders and no RCTs were identified focusing on poor or high responders., Wider Implications of the Findings: Clinicians should be informed that although biosimilars of follitropin alfa produce similar number of oocytes with the originator, pregnancy rates after a fresh transfer are likely to be lower. Future research should focus on optimizing the production and use of biosimilars of follitropin alfa, so that they lead to pregnancy rates comparable to the originator., Study Funding/competing Interest(s): No external funding was used for this study. K.I.K. and A.S. have no competing interest to disclose. E.M.K. reports personal fees and non-financial support from Merck, Ferring, IBSA, and Vianex. B.W.M. has been supported by an investigator grant from NHMRC, has received consulting fees from Organon, Merck, and Norgine, research support and non-financial support from Merck KGaA, Darmstadt, Germany. B.W.M. also reports having stocks from OBsEva. C.A.V. reports grants, personal fees, and non-financial support from Merck KGaA, Darmstadt, Germany, personal fees, and non-financial support from Merck, Sharpe and Dohme, personal fees and non-financial support from Organon, grants and non-financial support from Ferring, personal fees from IBSA, and personal fees and non-financial support from Gedeon Richter and Vianex., Registration Number: Protocol for the systematic review registered in The International Prospective Register of Systematic Reviews (PROSPERO; CRD42024498237)., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

The role of microbial terroir for enhancing the geographical origin of wines is well appreciated. Still, we lack a good understanding of the assembly mechanisms driving carposphere grapevine microbiota. We investigated the role of cultivar, vintage, terroir units (TUs), and vineyard geographic location on the composition of the carpospheric microbiota of three important cultivars in the viticultural zone of Drama, Greece using amplicon sequencing. Our strategy to define TUs based on georeferencing analysis allowed us to disentangle the effects of TU and vineyards geographic location, considered as a lumped factor in most studies to date. We hypothesized that (i) these factors contribute differently on the assembly of the carposphere microbiome and that (ii) fungal and bacterial communities follow different assembly mechanisms. Vintage and TU were the stronger determinants of the carposphere fungal and bacterial communities, although the latter showed weaker response. The stronger effect of TU over vineyard geography and cultivar reinforces the role of microbial terroir in viticulture. We identified fungi (Cladosporium, Aureobasidium, Alternaria) and bacteria (Pseudomonas, Methylobacterium, Sphingomonadaceae) as main members of the core microbiome. These microorganisms were associated with specific cultivars and TUs, a feature that could be pursued towards a new microbiome-modulated paradigm of viticulture., (© The Author(s) 2025. Published by Oxford University Press on behalf of FEMS.)

Background: Dermoscopy is a valuable tool in the diagnosis of various skin conditions. It increases sensitivity and specificity in skin cancer diagnosis, as well as in infectious, inflammatory and hair diseases. However, mastering the intricacies of dermoscopy can be challenging. In this context, innovative educational methods are sought, including game-based learning (GBL) strategies., Objectives: To describe current perceptions, knowledge and use of GBL strategies in dermoscopy education, and identify strengths and challenges to enhance their use., Methods: A web-based cross-sectional survey with 25 questions was distributed to members of the International Dermoscopy Society -between October 2022 and April 2023. Responses were collected and analysed using frequency analysis and graphical representation., Results: In total, 801 responses were received. Of these, 46.6% of respondents were unfamiliar with gamification and serious games. Among those acquainted with these concepts, 56.3% reported using GBL strategies for education. Younger participants were more likely to use GBL strategies (P = 0.02). Participants familiar with GBL believed it enhanced medical education (78.5%) but should not entirely replace traditional teaching methods (96.0%). For dermoscopy education specifically, 22.1% of respondents had used GBL strategies, with Kahoot! (35.5%) and YOUdermoscopy (24.1%) being the most commonly used platforms. Respondents found gaming strategies to be fun (95.5%), motivating (91.0%) and valuable for e-learning (94.4%)., Conclusions: Results from this survey demonstrate a favourable perception of GBL strategies in dermatology education, including dermoscopy. While there are ongoing challenges in validation, GBL strategies are promising and valuable tools that can aid the learning and teaching experience. Addressing implementation barriers and validating existing games could optimize the impact of GBL on dermatology education., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome., Methods: A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included., Results: Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated., Conclusions: In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Epidermolysis bullosa (EB) is a group of rare, severe, genetic disorders characterised by persistent skin fragility and open wounds. EB manifests as cutaneous and mucosal blistering, erosions and impaired wound healing., Objectives: To determine the long-term efficacy, tolerability and safety of Oleogel-S10 (birch bark extract) in dystrophic (DEB) and junctional (JEB) EB in the 24-months open-label phase (OLP) of the EASE study., Methods: EASE was a double-blind, randomised, controlled, phase III study consisting of two phases: a 90-day double-blind phase (DBP), and a 24-month OLP. Patients from both former treatment groups in the DBP entered the single-arm OLP (n = 205). Patients received Oleogel-S10 on all EB partial thickness wounds. OLP endpoints included: incidence, severity/relatedness of adverse events (AEs), wound infection maximum severity, changes in body surface area percentage (BSAP) of wounds, EB Disease Activity and Scarring Index (EBDASI), pain, itch, disease severity and quality of life outcomes., Results: The OLP data demonstrated Oleogel-S10 target wound treatment adherence was >99% and mean treatment duration was 584.7 days (±246.1 days). 71.7% of patients in the OLP were aged <18 years and 86.8% had DEB; recessive DEB predominated (78.0%). AEs were reported in 77.1% of patients and were typically mild-to-moderate. Severe and serious AEs were observed in 18.0% and 24.4% of patients, respectively. AEs resulted in the withdrawal of 7.8% of patients (n = 16), including three with treatment-related AEs. Nine deaths were reported: none attributable to treatment. Incidence of target wound infections was low (n = 7); five were mild-to-moderate and two severe. In patients treated with Oleogel-S10 throughout, mean (SD) BSAP changes from DBP baseline at 3, 12 and 24 months were -4.3% (8.1), P < 0.0001; -5.9% (8.6), P < 0.0001; -3.7% (9.0), P = 0.0026, respectively. Similarly, significant changes in EBDASI skin activity score from DBP baseline were observed: -3.9 (8.3), P < 0.0001; -5.1 (8.2), P < 0.0001; -3.0 (8.3), P = 0.0068, at 3, 12 and 24 months, respectively., Conclusions: These data support an encouraging long-term safety profile of Oleogel-S10, and a sustained reduction in wound burden over at least 24 months of Oleogel-S10 treatment., (© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Changes in retinal vessel caliber are crucial for detecting early retinopathy, a significant cause of blindness in individuals with Diabetes Mellitus type 2 (T2DM). This study aims to evaluate the changes in retinal vessel caliber and identify factors associated with these changes in recently diagnosed T2DM patients., Methods: The study included newly diagnosed T2DM patients (within 6 months of diagnosis) who were free of antidiabetic treatment (except metformin) and matched individuals based on age and blood pressure (BP). Data collected included somatometric measurements, BP (office and 24-hour), hematological data, albuminuria (via 24-hour urine collections), ten-year atherosclerotic cardiovascular disease risk (ASCVD score), endothelial dysfunction (measured by Asymmetric Dimethylarginine, ADMA), retinal microvascular changes, assessed as central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) using specialized software on non-mydriatic fundus photographs., Results: The study involved 87 T2DM patients and 90 controls, aged 57±11 years. Key findings include no significant differences in CRAE, CRVE, and AVR between T2DM patients and controls. Age (p=0.019) and nighttime systolic BP (SBP) (p=0.002) were independent predictors of AVR. CRAE was independently associated with nighttime SBP (p=0.048). CRVE was independently associated with age (p=0.016), dipping (p=0.002), and smoking (p=0.018). In normotensive subjects, AVR was significantly lower in T2DM patients (p=0.035)., Conclusions: The study concludes that increased nighttime SBP is a more critical factor than hyperglycemia in affecting retinal vascular caliber changes in newly diagnosed T2DM patients. This highlights the importance of managing nocturnal hypertension to prevent retinal damage in this patient population., (© The Author(s) 2025. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: Increased aortic blood pressure (BP) and arterial stiffness are associated with higher cardiovascular risk in hemodialysis. Previous works showed that lower dialysate sodium is associated with lower brachial-BP; data on aortic-BP and arterial stiffness are limited. This study aimed to investigate the effects of different dialysate sodium concentrations on 72-hour aortic-BP and arterial stiffness parameters in hemodialysis patients., Methods: This analysis is part of a prospective, non-randomized interventional study. Twenty-five hemodialysis patients underwent a set of 3 periods of different dialysate sodium concentrations; 6 sessions with dialysate sodium of 137 mEq/l, followed consecutively by 6 sessions with 139 mEq/l and, finally, 6 sessions with 141 mEq/l. At the start of the sixth hemodialysis session on each sodium concentration, 72-hour ABPM (Mobil-O-Graph) was performed to evaluate aortic-BP and arterial stiffness indices during the overall 72-hour, different 24-hour, daytime, and nighttime periods., Results: Mean 72-hour aortic systolic blood pressure (SBP)/diastolic blood pressure (DBP) were higher with increasing dialysate sodium concentrations (137 mEq/l: 114.2 ± 15.3/77.0 ± 11.8 mm Hg vs. 139 mEq/l: 115.4 ± 17.3/77.9 ± 14.0 mm Hg vs. 141 mEq/l: 120.5 ± 18.4/80.5 ± 14.7 mm Hg, P = 0.002/P = 0.057, respectively). Wave-reflection parameters (AIx, AIx(75), AP) were not significantly different between the 3 dialysate sodium concentrations. Ambulatory pulse wave velocity (PWV) was significantly higher with increasing dialysate sodium concentrations (137 mEq/l: 8.5 ± 1.7 m/s vs. 139 mEq/l: 8.6 ± 1.6 m/s vs. 141 mEq/l: 8.8 ± 1.6 m/s, P < 0.001). In generalized linear mixed models including 72-hour brachial SBP as a random covariate, the adjusted marginal means of 72-hour PWV were not significantly different between groups., Conclusions: This study showed that higher dialysate sodium concentrations are associated with significant increases in ambulatory aortic BP and PWV. These findings further support the need for modification of dialysate sodium concentration in hemodialysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Previous studies have reported that patients with Multiple Sclerosis (MS) face cognitive difficulties. Much less, however, is known about their language abilities. The present study aims to provide a clear view of the language abilities of adults with MS, considering their cognitive skills and the type of the disorder., Method: Specifically, 20 patients with Relapsing-Remitting MS, 17 patients with Secondary Progressive MS, and two healthy control groups demographically matched with the clinical groups, took part in the study. Their language abilities were examined using the Adult Language Abilities Test, which explores morpho-syntactic and semantic phenomena of the Greek language in both comprehension and production modes., Results: Our results did not reveal statistically significant differences between the two clinical groups on any cognitive or language subtest. Both groups, however, performed poorer than the control groups in producing the correct form of verbs, possessive and weak personal pronouns, and in comprehending relative and passive clauses. Participants' performance in morphosyntax was found to be related to their processing speed., Conclusion: Mapping the cognitive and language abilities of patients with MS is crucial for designing effective targeted interventions, which can help them adopt strategies to manage their specific cognitive and language symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Until recently, major bodies producing guidelines for the management of hypertension in patients with chronic kidney disease (CKD) disagreed in some key issues. In June 2023, the European Society of Hypertension (ESH) published the new 2023 ESH Guidelines for the management of arterial hypertension a document that was endorsed by the European Renal Association. Several novel recommendations relevant to the management of hypertension in patients with CKD appeared in these guidelines, which have been updated to reflect the latest evidence-based practices in managing hypertension in CKD patients. Most of these are in general agreement with the previous 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines-some reflect different emphasis on some topics (i.e. detailed algorithms on antihypertensive agent use) while others reflect evolution of important evidence in recent years. The aim of the present review is to summarize and comment on key points and main areas of focus in patients with CKD, as well as to compare and highlight the main differences with the 2021 KDIGO Guidelines for the management of blood pressure in CKD., Competing Interests: A.O. is one of the former Editors-in-Chief of CKJ. M.K. is member of the CKJ Editorial Board., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Formation of galactose-deficient IgA1 (Gd-IgA1) immunoglobulin is the initial step in the immunological cascade leading to IgA nephropathy (IgAN). Targeted-release budesonide (TRB), an evidence-based regimen without major side-effects, has recently been approved for IgAN treatment; herein we present our preliminary real-world data regarding prompt response to TRB., Methods: Patients with primary IgAN who remained with Uprot >1 g/24 h despite conventional treatment for 6 months were started on TRB, and re-evaluated at 3 (T3) and 6 (T6) months. Reduction of proteinuria by ≥30%, at T3 and T6 was regarded as very early (VER) and early response (ER), respectively. Kidney biopsies were evaluated according to Oxford classification (MEST-C) score., Results: Thirty-seven IgAN patients, male/female 26/11, mean ± standard deviation age 50.38 ± 14.32 years and mean time since diagnosis 45.65 ± 56.67 months, were included. Seventeen (45.94%) patients demonstrated VER, increasing to 29 (78.3%) as ER ( P  = .004). Patients who demonstrated VER had a shorter time interval since diagnosis compared with non-VER, 29.41 ± 6.96 vs 65.37 ± 17.64 months ( P  = .05), and preserved estimated glomerular filtration rate at diagnosis and T0, while time since diagnosis was the main factor associated with ER, 38.36 ± 19.6 vs 78.67 ± 18.64 months, in ER and non-ER respectively ( P  = .05). Patients with M0, E0, S0 and T0 had no significant changes during T0-T6, while patients with M1, E1, S1 and even T1 had significantly reduced proteinuria ( P  = .006, P  = .0011, P  < .0001 and P  < .0001, respectively)., Conclusions: Almost half of the patients showed proteinuria reduction after TRB treatment at 3 months, and the proportion increased significantly at 6 months. Patients likely to have a prompt proteinuria reduction were relatively close to diagnosis, retained kidney function and had active lesions in kidney biopsy., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

In a quarter of patients with ureterovaginal fistula (UVF), a concurrent associated vesicovaginal fistula (VVF) can also be found. An increased clinical suspicion should be arised in cases of urinary vaginal discharge accompanied with unilateral flank pain following a gynecological procedure. A 43-year-old female patient diagnosed with a complex postoperative UVF and VVF following a total hysterectomy. After an unsuccessful initial conservative approach with the placement of a nephrostomy tube, an ureterocystotomy with antireflux reimplantation of the ureter was decided. The patient experienced an uneventful postoperative period and a year later, the patient remains asymptomatic without any evidence of fistula recurrent. Our case reports the relatively rare presence of a concurrent postoperative complex UVF and VVF formation in order to rise clinical suspicion in clinicians regarding the diagnostic approach and optimal management., Competing Interests: Authors have no conflict of interest to declare., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: Brugada Syndrome (BrS) is a life-threatening cardiac arrhythmia disorder associated with an increased risk of ventricular arrhythmias (VAs) and sudden cardiac death. Current management primarily relies on implantable cardioverter-defibrillators (ICDs), but patients may experience ICD shocks. Catheter ablation (CA) has emerged as a potential intervention to target the arrhythmogenic substrate. This systematic review aims to evaluate the safety and efficacy of CA in BrS patients., Methods and Results: Studies with BrS patients undergoing CA for VAs were included. Fourteen studies that involved a total population of 709 BrS patients, with CA performed in 528 of them, were included. CA resulted in the non-inducibility of VAs in 91% (95% CI: 83-99, I2 = 76%) and resolution of type 1 ECG Brugada pattern in 88% (95% CI: 81-96.2, I2 = 91%) of the patients. After a mean follow-up of 30.7 months, 87% (95% CI: 80-94, I2 = 82%) of patients remained free from VAs. The incidence of VAs during follow-up was significantly lower in the ablation cohort in comparison to the group receiving only ICD therapy (OR = 0.03, 95% CI: 0.01-0.12, I2 = 0%)., Conclusion: CA shows potential as a therapeutic approach to reduce VAs and improve outcomes in BrS patients. While further research with a long follow-up period is required to confirm these findings, it represents a valuable tool as an add-on intervention to ICD implantation in BrS patients with a high burden of VAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: This article presents the novel BioASQ Synergy research process which aims to facilitate the interaction between biomedical experts and automated question-answering systems., Materials and Methods: The proposed research allows systems to provide answers to emerging questions, which in turn are assessed by experts. The assessment of the experts is fed back to the systems, together with new questions. With this iteration, we aim to facilitate the incremental understanding of a developing problem and contribute to solution discovery., Results: The results suggest that the proposed approach can assist researchers to navigate available resources. The experts seem to be very satisfied with the quality of the ideal answers provided by the systems, suggesting that such systems are already useful in answering open research questions., Discussion: BioASQ Synergy aspires to provide a tool that gives the experts easy and personalized access to the latest findings in a fast-growing corpus of material., Conclusion: In this article, we envisioned BioASQ Synergy as a continuous dialogue between experts and systems to issue open questions. We ran an initial proof-of-concept of the approach, in order to evaluate its usefulness, both from the side of the experts, as well as from the side of the participating systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Intradialytic hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137 mEq/L) compared with standard (140 mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH., Methods: In this randomized, single-blind, crossover study, 29 patients with IDH underwent four hemodialysis sessions with low (137 mEq/L) followed by four sessions with standard (140 mEq/L) dialysate sodium, or vice versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed., Results: Mean 48-h systolic/diastolic BP (SBP/DBP) were significantly lower with low compared with standard dialysate sodium concentration (137.6 ± 17.0/81.4 ± 13.7 mmHg with low vs 142.9 ± 14.5/84.0 ± 13.9 mmHg with standard dialysate sodium, P = .005/P = .007, respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3 ± 22.3/91.2 ± 15.1 mmHg with low vs 166.6 ± 17.3/94.5 ± 14.9 mmHg with standard dialysate sodium, P < .001/P = .134, respectively) and intradialytic (141.4 ± 18.0/85.0 ± 13.4 mmHg with low vs 147.5 ± 13.6/88.1 ± 12.5 mmHg with standard dialysate sodium, P = .034/P = .013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B lines were also significantly decreased with low dialysate sodium., Conclusions: Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH., Trial Registration: ClinicalTrials.gov study number NCT05430438., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Aims: Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF., Methods: Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses., Results: Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80-1.17], cardiovascular mortality (HR 1.04, 95% CI .72-1.49), thromboembolism (HR 1.06, 95% CI .87-1.28), stroke (HR 1.06, 95% CI .84-1.34), hospitalization (HR 1.34, 95% CI .89-2.02), and myocardial infarction (HR .98, 95% CI .70-1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19-1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54-.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76-1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33-2.03) and ablation therapy (OR 1.47, 95% CI 1.06-2.05) compared to asymptomatic cases., Conclusions: The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the 2021 report in presenting cardiovascular disease (CVD) statistics for the ESC member countries. This paper examines inequalities in cardiovascular healthcare and outcomes in ESC member countries utilizing mortality and risk factor data from the World Health Organization and the Global Burden of Disease study with additional economic data from the World Bank. Cardiovascular healthcare data were collected by questionnaire circulated to the national cardiac societies of ESC member countries. Statistics pertaining to 2022, or latest available year, are presented. New material in this report includes contemporary estimates of the economic burden of CVD and mortality statistics for a range of CVD phenotypes. CVD accounts for 11% of the EU's total healthcare expenditure. It remains the most common cause of death in ESC member countries with over 3 million deaths per year. Proportionately more deaths from CVD occur in middle-income compared with high-income countries in both females (53% vs. 34%) and males (46% vs. 30%). Between 1990 and 2021, median age-standardized mortality rates (ASMRs) for CVD decreased by median >50% in high-income ESC member countries but in middle-income countries the median decrease was <12%. These inequalities between middle- and high-income ESC member countries likely reflect heterogeneous exposures to a range of environmental, socioeconomic, and clinical risk factors. The 2023 survey suggests that treatment factors may also contribute with middle-income countries reporting lower rates per million of percutaneous coronary intervention (1355 vs. 2330), transcatheter aortic valve implantation (4.0 vs. 153.4) and pacemaker implantation (147.0 vs. 831.9) compared with high-income countries. The ESC Atlas 2023 report shows continuing inequalities in the epidemiology and management of CVD between middle-income and high-income ESC member countries. These inequalities are exemplified by the changes in CVD ASMRs during the last 30 years. In the high-income ESC member countries, ASMRs have been in steep decline during this period but in the middle-income countries declines have been very small. There is now an important need for targeted action to reduce the burden of CVD, particularly in those countries where the burden is greatest., (© European Society of Cardiology 2024.)

Aims: Pericoronary adipose tissue (PCAT) attenuation obtained by coronary computed tomography angiography (CCTA) has been associated with coronary inflammation and outcomes. Whether PCAT attenuation is predictive of major adverse cardiac events (MACE) during long-term follow-up is unknown., Methods and Results: Symptomatic patients with coronary artery disease (CAD) who underwent CCTA were included, and clinical outcomes were evaluated. PCAT was measured at all lesions for all three major coronary arteries using semi-automated software. A comparison between patients with and without MACE was made on both a per-lesion and a per-patient level. The predictive value of PCAT attenuation for MACE was assessed in Cox regression models. In 483 patients (63.3 ± 8.5 years, 54.9% men), 1561 lesions were analysed over a median follow-up duration of 9.5 years. The mean PCAT attenuation was not significantly different between patients with and without MACE. At a per-patient level, the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE were 0.970 (95% CI: 0.933-1.008, P = 0.121) when the average of all lesions per patient was analysed, 0.992 (95% CI: 0.961-1.024, P = 0.622) when only the most obstructive lesion was evaluated, and 0.981 (95% CI: 0.946-1.016, P = 0.285) when only the lesion with the highest PCAT attenuation per individual was evaluated. Adjusted HRs for vessel-specific PCAT attenuation in the right coronary artery, left anterior descending artery, and left circumflex artery were 0.957 (95% CI: 0.830-1.104, P = 0.548), 0.989 (95% CI: 0.954-1.025, P = 0.550), and 0.739 (95% CI: 0.293-1.865, P = 0.522), respectively, in predicting long-term MACE., Conclusion: In patients referred to CCTA for clinically suspected CAD, PCAT attenuation did not predict MACE during long-term follow-up., Competing Interests: Conflict of interest: The Department of Cardiology of Leiden University Medical Center received research grants from Abbott Vascular, Bayer, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. J.J.B. received speaker fees from Abbott Vascular, Edwards Lifesciences, and Omron. J.W.J. received research grants from and/or was speaker (with or without lecture fees) on a.o.(CME accredited) meetings sponsored by Amarin, Amgen, Athera, Biotronik, Boston Scientific, Dalcor, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, the Netherlands Heart Foundation, CardioVascular Research the Netherlands (CVON), the Netherlands Heart Institute, and the European Community Framework KP7 Programme. J.K. received consultancy fees from GE Healthcare and Synektik Pharma and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer, and Merck, outside of the submitted work. A.S. received consultancy fees from Astra Zeneca and Pfizer and speaker fees from Abbott, Astra Zeneca, BMS, Janssen, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: We investigated the feasibility of the RehaCom cognitive rehabilitation software in illiterate and low-educated individuals with mild cognitive impairment (MCI) and its clinical effectiveness in improving cognitive functions., Methods: Twenty illiterate or low-educated individuals with MCI were randomly assigned to an intervention (IG; n = 10) and control group (CG; n = 10). The IG participated in the cognitive enhancement program for 6 weeks, twice a week and a duration of 50-60 min for each session, while the CG did not receive any kind of intervention., Results: The two groups were demographically matched. The IG successfully completed all sessions of the cognitive enhancement program. A within-subject comparison between baseline and post-intervention assessment of cognitive functions indicated that the IG improved significantly on all administered neuropsychological tests, in contrast to the CG, whose performance remained stable between baseline and final assessment. A between-group comparison found statistically significant differences between the IG and CG groups on the Hindi Mental State Examination, Mini-Mental State Examination, and on delayed memory and recognition tasks, in favor of the IG., Conclusions: The findings of the present study support the feasibility of applying computerized cognitive enhancement programs to illiterate and low-educated individuals. Moreover, these programs appear to contribute positively to improving the cognitive functions of this population group. In order to generalize and confirm similar findings in a broader population of illiterate and low-educated individuals, future studies should include larger samples, possibly with longer duration of treatment and control groups that will receive non-targeted interventions as placebo interventions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Anaemia is a common complication of chronic kidney disease (CKD) and is associated with poor long-term outcomes and quality of life. The use of supplemental iron, erythropoiesis-stimulating agents (ESAs) and blood transfusions has been the mainstay for treatment of anaemia in CKD for more than 3 decades. Despite available treatments, CKD patients with anaemia are undertreated and moderate-severe anaemia remains prevalent in the CKD population. Anaemia has consistently been associated with greater mortality, hospitalization, cardiovascular events and CKD progression in CKD patients, and the risk increases with anaemia severity. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors have a novel mechanism of action by mimicking the body's response to hypoxia and have emerged as an alternative to ESAs for treatment of anaemia in CKD. Their efficacy in correcting and maintaining haemoglobin has been demonstrated in >30 phase 3 clinical trials. Additionally, HIF activation results in various pleiotropic effects beyond erythropoiesis, with cholesterol reduction and improved iron homeostasis and potential anti-inflammatory effects. The long-term safety of these agents, particularly with respect to cardiovascular and thromboembolic events, and their possible effect on tumour growth needs to be fully elucidated. This article presents in detail the effects of HIF-PH inhibitors, describes their mechanisms of action and pharmacologic properties and discusses their place in the treatment of anaemia in CKD according to the available evidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Research on lean, energy-deficient athletic and military cohorts has broadened the concept of the Female Athlete Triad into the Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum of abnormalities induced by low energy availability (LEA), which serves as the underlying cause of all symptoms described within the REDs concept, affecting exercising populations of either biological sex. Both short- and long-term LEA, in conjunction with other moderating factors, may produce a multitude of maladaptive changes that impair various physiological systems and adversely affect health, well-being, and sport performance. Consequently, the comprehensive definition of REDs encompasses a broad spectrum of physiological sequelae and adverse clinical outcomes related to LEA, such as neuroendocrine, bone, immune, and hematological effects, ultimately resulting in compromised health and performance. In this review, we discuss the pathophysiology of REDs and associated disorders. We briefly examine current treatment recommendations for REDs, primarily focusing on nonpharmacological, behavioral, and lifestyle modifications that target its underlying cause-energy deficit. We also discuss treatment approaches aimed at managing symptoms, such as menstrual dysfunction and bone stress injuries, and explore potential novel treatments that target the underlying physiology, emphasizing the roles of leptin and the activin-follistatin-inhibin axis, the roles of which remain to be fully elucidated, in the pathophysiology and management of REDs. In the near future, novel therapies leveraging our emerging understanding of molecules and physiological axes underlying energy availability or lack thereof may restore LEA-related abnormalities, thus preventing and/or treating REDs-related health complications, such as stress fractures, and improving performance., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20-65% in diabetic and 30-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training (ET) have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining ET and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of ET in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and healthcare professionals of the potential of exercise therapy in order to encourage implementation of ET in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3-G5D., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients)., Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied., Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment., Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

The activins-follistatins-inhibins (AFI) hormonal system affects bone metabolism. Treatments that alter bone metabolism may also alter the AFI molecules. In this non-randomized, open-label, head-to-head comparative study, circulating levels of the AFI system were evaluated in postmenopausal women with osteoporosis treated for 12 mo with either teriparatide (n = 23) or denosumab (n = 22). Τeriparatide treatment increased activin B (P=.01) and activin AB (P=.004) and the ratios activin A/follistatin (P=.006), activin B/follistatin (P=.007), activin AB/follistatin (P<.001), and activin AB/ follistatin-like 3 (FSTL3) (P=.034). The significant P for trend in group × time interactions of activins B and AB and of the ratio activin AB/FSTL3 remained robust after adjustment for BMI and LS BMD but it was lost for activin B after adjustment for previous antiresorptive treatment. The effect of teriparatide on BMD was attenuated when it was adjusted for baseline activins levels or their 12-mo changes. No changes were observed after denosumab treatment. In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner. Future studies are needed to study the potentially important role activins may play in bone biology and any associations with the effect of teriparatide on BMD. Clinical Trials identifier: NCT04206618. ClinicalTrials.gov  https://clinicaltrials.gov/search?term=NCT04206618., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry., Methods: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines., Results: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories., Conclusion: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission., Trial Registration: Clinicaltrials.gov, NCT01357668., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)