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Background: Too high or too low patient volumes and work amounts may overwhelm health care professionals and obstruct processes or lead to inadequate personnel routine and process flow. We sought to evaluate, whether an association between current caseload, current workload, and outcomes exists in intensive care units (ICU)., Methods: Retrospective cohort analysis of data from an Austrian ICU registry. Data on patients aged ≥ 18 years admitted to 144 Austrian ICUs between 2013 and 2022 were included. A Cox proportional hazards model with ICU mortality as the outcome of interest adjusted with patients' respective SAPS 3, current ICU caseload (measured by ICU occupancy rates), and current ICU workload (measured by median TISS-28 per ICU) as time-dependent covariables was constructed. Subgroup analyses were performed for types of ICUs, hospital care level, and pre-COVID or intra-COVID period., Results: 415 584 patient admissions to 144 ICUs were analysed. Compared to ICU caseloads of 76 to 100%, there was no significant relationship between overuse of ICU capacity and risk of death [HR (95% CI) 1.06 (0.99-1.15), p = 0.110 for > 100%], but for lower utilisation [1.09 (1.02-1.16), p = 0.008 for ≤ 50% and 1.10 (1.05-1.15), p < 0.0001 for 51-75%]. Exceptions were significant associations for caseloads > 100% between 2020 and 2022 [1.18 (1.06-1.30), p = 0.001], i.e., the intra-COVID period. Compared to the reference category of median TISS-28 21-30, lower [0.88 (0.78-0.99), p = 0.049 for ≤ 20], but not higher workloads were significantly associated with risk of death. High workload may be associated with higher mortality in local hospitals [1.09 (1.01-1.19), p = 0.035 for 31-40, 1.28 (1.02-1.60), p = 0.033 for > 40]., Conclusions: In a system with comparably high intensive care resources and mandatory staffing levels, patients' survival chances are generally not affected by high intensive care unit caseload and workload. However, extraordinary circumstances, such as the COVID-19 pandemic, may lead to higher risk of death, if planned capacities are exceeded. High workload in ICUs in smaller hospitals with lower staffing levels may be associated with increased risk of death., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Maternal vaccination during pregnancy, in general and against COVID-19 infection, offers protection to both mother and baby, but uptake remains suboptimal. This study aimed to explore the perceptions regarding COVID-19 vaccination in pregnancy, particularly for marginalised populations and those living with social or medical complexity. A total of 96 semi-structured in-depth interviews were conducted with 40 women, 15 partners, 21 HCPs, and 20 policy makers, across all four nations of the United Kingdom (UK), discussing their lived experience of utilising, delivering, or developing policy for COVID-19 vaccination in pregnancy during the pandemic. Three themes were derived: (1) historical and social context, (2) communication of information and guidance, and (3) appraisal and action. Together these captured the participants' legacy of mistrust in drugs during pregnancy; prior positive experiences; concerns about missing information, conflicting information, or false information about COVID-19 vaccines; and confusing guidance for pregnant women. The final theme describes the participants' behaviour and actions undertaken consequent to their experiences and the available information. The findings suggest efforts to improve COVID-19 vaccination in pregnancy may be best focused on personalised communication of information. A trusting relationship and prior positive experiences with other vaccines, both in and outside of pregnancy, positively influenced perceptions of COVID-19 vaccination.

Bruck syndrome is a rare, autosomal-recessive condition associated with features of both arthrogryposis and osteogenesis imperfecta. It is characterised by congenital large joint contractures with pterygia and bone fragility, leading to fractures and deformities, along with a short stature caused by progressive skeletal deformities. There are fewer than 50 described cases of Bruck syndrome in the literature, with no reported cases in pregnancy. We describe a case of a successful pregnancy in a woman with Bruck syndrome.In pregnant women with Bruck syndrome, we recommend a multidisciplinary approach including input from obstetric and fetal medicine specialists, midwives, anaesthetists, geneticists, occupational therapists and physiotherapists., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: As part of their religious obligation, Muslims abstain from food and drink from dawn until dusk for a 30-day period during Ramadan. Fasting may affect daily functioning, such as increased risk of collision for drivers. A study of the impact of fasting during Ramadan on trauma incidence may allow for the creation of public health campaigns targeting this potential phenomenon. We aimed to determine whether trauma incidence increases during Ramadan, and to characterise the trauma occurring during Ramadan., Methods: Both published and unpublished literature, along with conference proceedings and reference lists from the selected studies, were searched up until the 1 st of July 2023. A narrative synthesis was conducted, and the included studies were evaluated using appropriate tools based on their study design., Results: Seventeen studies (964,631 subjects) were included. There were methodological concerns pertaining to their low level of evidence and risk of bias. Of nine studies reporting on road traffic accidents (RTAs), six found a higher incidence during Ramadan. Road traffic accidents and occupational injuries (OIs) were more likely to occur near or at sunset (marking the end of the fast). Two studies presented conflicting evidence regarding the effect of fasting in Ramadan on sports-associated injuries. Current evidence suggests that falls and violence-related trauma do not occur more frequently during Ramadan, with insufficient evidence to determine the occurrence of other injury mechanisms., Conclusion: Individuals who fast may be at a higher risk of RTAs and OIs during Ramadan than outside this month. Due to the lack of studies performed in the Americas and Europe, it is unclear whether the findings are applicable to these regions. Current evidence is limited by lack of stratification according to time of trauma occurrence, and high risk of bias., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Co-author is Associate Editor of Heliyon - C.K If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Objectives: Obesity levels and mortality from breast cancer are higher in more deprived areas of the UK, despite lower breast cancer incidence. Supplemental imaging for women with dense breasts has been proposed as a potential improvement to screening, but it is not clear how stratification by percentage mammographic density (%MD) would be reflected across socioeconomic groups. This study aims to clarify the associations between breast composition (dense and fatty tissue) and socioeconomic status in a multi-ethnic screening population., Methods: Demographic characteristics were collected for 62,913 participants in a UK breast screening programme (age, ethnicity, Index of Multiple Deprivation (IMD)). Automated mammographic measurements were derived: dense volume (DV), non-dense volume (NDV) and percent density (%MD). Correlations between deprivation and mammographic composition were examined before and after adjustment for age, ethnicity and NDV, using non-dense breast volume as a proxy for body mass index (BMI)., Results: There was negligible correlation between deprivation and DV (r = 0.017; P  < 0.001 in all cases), but NDV increased with increasing deprivation (Pearson r = 0.101). Correlations were weaker in the Asian and Chinese ethnic groups. %MD decreased with deprivation (r = -0.094) and adjustment for ethnicity did not alter the association between %MD and IMD (relative change, most to least deprived quintile IMD: 1.18; 95% confidence interval: 1.16, 1.21)., Conclusions: Deprivation-related differences in %MD in the screening population are largely explained by differences in breast fat volume (NDV) which reflects BMI. Women in more deprived areas, where obesity and breast cancer mortality rates are higher, have increased breast adiposity and may miss out on risk-adapted screening if stratification is based solely on %MD or BIRADS classification., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The novel Confirm Rx™ implantable cardiac monitor (ICM) with SharpSense™ technology incorporates a new P-wave discriminator designed to improve AF detection. This study aimed to evaluate the diagnostic performance of the Confirm Rx™ ICM in detecting AF episodes of varying durations., Methods: We conducted a multicenter retrospective analysis of consecutive patients implanted with a Confirm Rx™ ICM (v1.2) across nine UK hospitals, all with documented AF lasting at least 6 min. Electrocardiograms (ECGs) were manually adjudicated by cardiologists. To account for intra- and inter-reviewer variability, a random sample of 10% of ECGs underwent additional review. Disagreements were resolved by a third reviewer. Diagnostic performance was determined by calculating the gross and patient-averaged positive predictive value (PPV) for AF episodes of different duration. The source of false positive (FP) detection was also categorized., Results: Overall, 16,230 individual ECGs from 232 patients were included. The median AF episode duration was 14 min. R-wave amplitude remained stable during follow-up (0.52 ± 0.27 mV [initial] vs. 0.54 ± 0.29 mV [end of follow-up], p  = .10). The gross and patient-averaged PPV were 75.0% and 67.0%, respectively. Diagnostic performance (gross) increased with progressively longer AF episodes: 88.0% for ≥1 h, 97.3% for 6 h, and 100% for 24 h. The main source of FP during tachycardia was T-wave oversensing (54.2%), while in non-tachycardic episodes it was predominantly ectopy (71.2%). The AF burden precision was excellent (93.3%)., Conclusion: The Confirm Rx™ ICM diagnostic performance was modest for all AF episodes (75%), with accuracy increasing for longer AF episodes., Competing Interests: ABG, RSG, and TB have received financial support for research from Abbott. MTBP received financial support to attend scientific meetings from Acutus Medical. HT received financial support to attend scientific meetings from Abbott, BSCI, Medtronic, and Boston Scientific. DW has received financial support to attend scientific meetings. AJS, AB, JRP, ML, NC, MGM, RB, JO, and DF– no conflicts in relation to this paper., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Magnetic resonance enterography [MRE] and intestinal ultrasound [IUS] have developed rapidly in the past few decades, emerging as the primary non-invasive options for both diagnosing and monitoring Crohn's disease [CD]. In this review, we evaluate the pertinent data relating to the use of MRE and IUS in CD. We summarise the key imaging features of CD activity, highlight their increasing role in both the clinical and the research settings, and discuss how these modalities fit within the diagnostic pathway. We discuss how they can be used to assess disease activity and treatment responsiveness, including the emergence of activity scores for standardised reporting. Additionally, we address areas of controversy such as the use of contrast agents, the role of diffusion-weighted imaging, and point-of-care ultrasound. We also highlight exciting new developments, including the applications of artificial intelligence. Finally, we provide suggestions for future research priorities., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management?, Methods: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK. Semi-structured interviews explored lived experiences of carriers' access to care with a focus on decision support. Themes were constructed using framework analysis. These were developed into a conceptual model with recommendations for codevelopment of improved information and support including a tailored decision aid to complement integrated healthcare., Results: Twenty participants included 12 women and eight men, half with a history of cancer. Six overarching themes were: (1) finding balance with Lynch; (2) living 'on higher alert'; (3) managing uncertainty: 'I've thought about it a lot'; (4) burden of responsibility: 'It's on me'; (5) access to joined-up care and support: 'There's something missing'; and (6) influence/pressure from others., Conclusions: This qualitative interview study provided in-depth insights from Lynch syndrome carriers about their lived experiences, informed by their values. Recommendations to empower carriers to make sense of genetic cancer risks and support decisions included accessible, trusted information, educated healthcare professionals, shared decision making, and joined-up integrated care pathways complemented by tailored decision aids., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Undifferentiated plant and animal stem cells are essential for cell, tissue, and organ differentiation, development, and growth. They possess unusual antiviral immunity which differs from that in specialized cells. By comparison to animal stem cells, we discuss how plant stem cells defend against viral invasion and beyond., Competing Interests: Declaration of interests The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Laparoscopic fundoplication remains the standard treatment for patients with severe gastro-oesophageal reflux disease (GORD). Multiple randomised controlled trials (RCTs) have compared the two most commonly performed surgical techniques, total and posterior partial fundoplication (Nissen [NF] and Toupet [TF]), in terms of symptom control and treatment failure in patients without subsequent dysmotility disorders. We aimed to conduct a systematic review and meta-analysis of these two techniques with regard to the long-term effect on reflux control and associated dysphagia., Methods: The MEDLINE ® , Embase ® , PubMed ® and Cochrane Library databases were searched, and all the relevant published RCTs were shortlisted according to the inclusion criteria. The summated outcomes of long-term results relating to the recurrence of GORD and dysphagia were evaluated in a meta-analysis using RevMan software., Results: Eight studies (all RCTs) on 1,545 patients undergoing NF or TF were eligible for inclusion in this meta-analysis. There were 799 patients in the NF group and 746 in the TF group. In the random effects model analysis, the incidence of long-term recurrence of GORD was not statistically different between the NF and TF cohorts (odds ratio [OR]: 0.69, 95% confidence interval [CI]: 0.34-1.41, z=1.01, p =0.31). However, the incidence of long-term dysphagia was statistically lower in the TF group (OR: 2.92, 95% CI: 1.49-5.72, z=3.13, p =0.002) with low between-study heterogeneity (I 2 =0%)., Conclusions: The findings of this systematic review and meta-analysis on symptomatic GORD appear to be in favour of partial posterior fundoplication (TF) as the optimal treatment. It provides equivalent outcomes in reflux symptom control with a lower risk of postoperative dysphagia compared with total fundoplication (NF).

Aims: To update the European Society of Cardiology (ESC) quality indicators (QIs) for the evaluation of the care and outcomes of adults with heart failure., Methods and Results: The Working Group comprised experts in heart failure including members of the ESC Clinical Practice Guidelines Task Force for heart failure, members of the Heart Failure Association, and a patient representative. We followed the ESC methodology for QI development. The 2023 focused guideline update was reviewed to assess the suitability of the recommendations with strongest association with benefit and harm against the ESC criteria for QIs. All the new proposed QIs were individually graded by each panellist via online questionnaires for both validity and feasibility. The existing heart failure QIs also underwent voting to 'keep', 'remove' or 'modify'. Five domains of care for the management of heart failure were identified: (1) structural QIs, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) patient health-related quality of life. In total, 14 'main' and 3 'secondary' QIs were selected across the five domains., Conclusion: This document provides an update of the previously published ESC QIs for heart failure to ensure that these measures are aligned with contemporary evidence. The QIs may be used to quantify adherence to clinical practice as recommended in guidelines to improve the care and outcomes of patients with heart failure., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Digital self-management platforms have been proposed as a solution to better support people manage their musculoskeletal (MSK) condition. However, research studies often explicitly exclude people who can't access internet connected devices. An important consideration is that digital exclusion (for people without access to an internet connected device) from these new digital options will worsen already existing inequality and inequity in healthcare., Aim: To evaluate the acceptability and potential causes of digital exclusion of the South West London (SWL) MSK self-management app., Objectives: (1) Explore why some patients are not using the app and any barriers they have. Explore why some clinicians are not prescribing the app. (2) Make recommendations, based on these findings, to improve digital inclusion., Methods/design: An explanatory sequential mixed method service evaluation that consisted of initial questionnaires to identify suitable collaborators, followed by structured interviews of patients and clinicians., Results: Following a comprehensive data analysis, 10 sub-themes were grouped into four main themes: (1) Beliefs: Importance of understanding the role of digital; face to face consultation is still valued and needed. (2) Barriers: Lack of digital literacy; lack of physical examination/contact with a clinician. (3) Enablers: Immediate access to advice and information; perceived better control over health; ease of use; no appointment needed. (4) Solutions: Support and training; greater awareness., Conclusions: As digital health technology develops, strategies must change, requiring deliberate work and investments to improve inclusion. Our findings highlight how digital technology design and delivery can be adapted to address the causes of digital exclusion., (© 2024 John Wiley & Sons Ltd.)

Aims: As the future workload of interventional radiologists in the UK continues to expand, it is imperative that current IR trainees are given maximal opportunities to expand their skill sets. This paper argues that opportunities for involvement in international collaborative fieldwork should be expanded for interventional radiology trainees in the UK, as a means of maximising their future competency and positive contribution to the advancement of global healthcare. The study builds upon first-hand experience of the authors in the field and a review of the relevant literature., Materials and Methods: This scoping review aimed to ascertain the current global health opportunities for interventional radiology trainees primarily in Resource Limited Countries (RLCs). This review further contrasted these opportunities with ones provided to trainees within North America and European countries., Results: This review found that the opportunities for international collaborative fieldwork for UK interventional radiology trainees are sparse. The availability of such opportunities in the US is significantly greater as is the awareness and appreciation of the benefits of such international collaborations for trainees. Benefits include greater experience with a variety of pathologies, a potentially larger volume of workload, improved cultural competency and proficiency and greater cost-conscious and more sustainable practices. It is also pertinent that any future global partnership opportunities for UK clinicians are crafted with care to benefit both UK and international healthcare professionals, institutions and patients within RLCs., Conclusion: Significant work is needed to expand opportunities for global health for interventional radiology trainees in the UK. It is incumbent upon the major radiology societies and educational bodies within the UK to expand upon such opportunities to develop a robust, world-leading workforce, which would subsequently enhance our global health positionality and reflexivity., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Severe burns are a major component of conflict-related injuries and can result in high rates of mortality. Conflict and disaster-related severe burn injuries present unique challenges in logistic, diagnostic and treatment options, while wider conflict is associated with driving local antimicrobial resistance. We present a targeted review of available literature over the last 10 years on the use of systemic antimicrobial antibiotics in this setting and, given limited available data, provide an expert consensus discussion. While international guidelines do not tend to recommend routine use of prophylactic systemic antibiotics, the challenges of conflict settings and potential for polytrauma are likely to have ongoing impacts on antimicrobial decision-making and use. Efforts must be made to develop a suitable evidence base in this unique setting. In the interim, a pragmatic approach to balancing selective pressures of antimicrobial use with realistic access is possible., Competing Interests: Declaration of Competing Interest LSPM has consulted for or received speaker fees from bioMerieux (2013–2024), Eumedica (2016–2022), Pfizer (2018–2024), Sumitovant (2021–2023), Shionogi (2021–2024), Qiagen (2023), and Gilead (2024) and received research grants from the National Institute for Health Research (2013–2024), CW+ Charity (2018–2024), North West London Pathology (2022–2024), LifeArc (2020–2022), Shionogi (2024), and the Healthcare Infection Society (2024). SJCP has received research grants from the Hospital Infection Society, John Muir Trust and the Drummond Foundation not in connection with this work. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: Indications and clinical impact of genetic testing for cardiac diseases have increased significantly over the past years. The aim of this physician-based European Heart Rhythm Association (EHRA) survey was to assess current clinical practice and access to genetic testing for cardiac diseases across European Society of Cardiology countries and to evaluate adherence to the 2022 EHRA/HRS/APHRS/LAHRS Expert Consensus Statement on genetic testing., Methods and Results: An online questionnaire composed of 28 questions was submitted to the EHRA Research Network and European Reference Network GUARD-Heart healthcare partners and promoted via dedicated social media channels. There were 357 respondents from 69 countries, 40% working in a hospital setting with a cardiac genetic service and/or a dedicated clinic focusing on inherited cardiac diseases and 27% with an onsite genetic laboratory. No genetic testing or low annual rate (<10/year) was declared by 39% of respondents. The majority of respondents (78%) declared issues or limitations to genetic testing access in their clinical practice. The main reasons for not providing or limited access to genetic testing were no availability of dedicated unit or genetic laboratory (35%) or reimbursement issues (25%). The most frequently reported indication for genetic testing was diagnostic purpose (55%). Most respondents (92%) declared offering genetic testing preceded by genetic counselling and 42% regular multidisciplinary evaluations for patients with cardiac genetic diseases. The perceived value of genetic testing in the diagnostic, prognostic, and therapeutic assessment was variable (67, 39, and 29%, respectively) and primarily based on the specific inherited disease. The majority of respondents recommended cascade genetic testing for the first-degree family members in case of pathogenic/likely pathogenic variant in the proband., Conclusion: This survey highlights a significant heterogeneity of genetic testing access and provision and issues attributable to the availability of dedicated unit/genetic laboratory and reimbursement. However, adequate adherence to indications in the current recommendations for genetic testing in patients with cardiac diseases was observed., 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: Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking., Aim: To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer., Design and Setting: An epidemiological modelling study for women in England using the BOADICEA breast cancer prediction model and data relating to MHT use and breast cancer risk taken from research by the Collaborative Group on Hormonal Factors in Breast Cancer., Method: The risk of developing and dying from breast cancer between the ages of 50 and 80 years was modelled in women with four different breast cancer family history profiles: 'average', 'modest', 'intermediate', and 'strong' by using 1) background risks of breast cancer by age and family history, 2) relative risks for breast cancer associated with MHT use, and 3) 10-year breast cancer-specific net mortality rates. This study modelled use of combined oestrogen-progestogen MHT (cyclical or continuous) and oestrogen-only MHT., Results: For a woman of 'average' family history taking no MHT, the cumulative breast cancer risk (age 50-80 years) is 9.8%, and the risk of dying from the breast cancer is 1.7%. In this model, 5 years' exposure to combined-cyclical MHT (age 50-55 years) was calculated to increase these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative breast cancer risk is 19.6% (age 50-80 years), and the risk of dying from the breast cancer is 3.2%. With 5 years' exposure to MHT (age 50-55 years), this model showed that these risks increase to 22.4% and 3.5%, respectively., Conclusion: In this model, both family history and MHT are associated with increased risk of breast cancer. Estimates of the risks of breast cancer associated with MHT for women with different family histories can be used to support decision making around MHT prescription for women experiencing menopausal symptoms., (© The Authors.)

This study evaluated service use of children and young people with medically unexplained symptoms (MUS) referred to a Paediatric Psychology Service between 2008 and 2017. Univariate analyses of activity data indicated that the MUS group (n=268) required more clinical sessions than other patients (n=3577) (inpatient MUS: 7.5 (12.5) vs general: 4.0 (6.0), p=0.006; outpatient: MUS 10.7 (15.0) vs general 6.3 (8.9), p<0.001). Multivariate analyses confirmed that MUS group status remained significantly associated (p<0.001) with a higher number of contacts, even when age and gender were controlled for. Although both groups benefitted equally from psychological input, MUS referrals required more contact time than general referrals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The British Orthopaedic Association Standards for Trauma-4 includes pediatric Gustilo-Anderson type I upper limb open fractures and recommends surgical debridement as the preferred method of treatment. The reported incidence of fracture-related infection is low in patients with this injury pattern and the evidence supporting debridement is therefore weak. The aim of this systematic review is to compare infection rates between non-operative management and operative debridement in children with Gustilo I upper limb fractures who did not require surgical fixation., Methods: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligibility criteria included patients <18 years with Gustilo-Anderson type I upper limb fractures managed with either antibiotics alone or with operative debridement. Patients in whom the fracture was stabilized were excluded, and the Risk Of Bias In Non-randomized Studies-of Interventions tool was used to evaluate bias., Results: Eleven, predominantly retrospective studies were identified, involving 537 patients with fractures including 466 forearm, 70 wrist, and one humerus. A non-operative management strategy was used in 293 patients with one superficial infection (0.3%). Operative debridement was used in 244 patients with one superficial infection (0.4%)., Conclusion: The optimal management of Gustilo-Anderson type I pediatric upper limb fractures is unclear. Based on the current evidence base, surgical debridement does not appear to reduce the rate of infection. The decision to manage these injuries aggressively should therefore be individualized to consider patient age, mechanism, and clinical extent of injury., Level of Evidence: level II., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors request that the following individuals not be approached to review our manuscript as they are listed as co-authors: Ms Y.G., BSc, MD, PhD, St George’s University Hospitals NHS Foundation Trust, London, UK and Mr F.M., MBBChB, MSc, PhD, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK., (© The Author(s) 2024.)

Competing Interests: Conflict of interest: None declared.

Importance: Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain., Objective: To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis., Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis., Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first., Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality., Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different., Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

Introduction: The COVID-19 pandemic led to a significant reduction in operative exposure for surgical trainees, necessitating alternative training methods to mitigate the impact on surgical education. This study sought to evaluate whether minimally invasive surgery (MIS) skills could be taught remotely using widely available technology with objective assessments of proficiency., Methods: This was a pilot observational study with comparative assessment of face-to-face (F2F) and virtual training of novice learners in MIS skills. Performance and objective cognitive workload parameters (Surgical Task Load Index (SURG-TLX) score, heart rate and pupil metrics) were evaluated. The assessments were peg transfer (McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS)) and suturing (Suturing Training and Testing (SUTT)) tasks performed using box trainers. Virtual teaching was conducted by expert trainers using a web-based streaming platform., Results: Technical challenges of delivering a virtual MIS skills course were addressed after a pilot course. Participants (n = 20) in the final course had similar baseline characteristics and were randomly allocated to F2F (n = 8) and virtual (n = 12) teaching groups. Participants in the online group completed the peg transfer task faster than the F2F group (11.25 minutes vs. 16.88 minutes; P = 0.015). There were no significant differences in all other MISTELS and SUTT performance measures between groups. Cognitive workload parameters (SURG-TLX score, heart rate and pupil metrics) were also similar between groups., Conclusion: This study has demonstrated that virtual teaching of MIS skills using a web-based streaming platform is feasible and effective, providing the foundation for low-cost, effective, and scalable MIS skills programs in the future., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Brain health means optimal physiological brain function across the normal life-course. It encompasses not only healthy brain aging but also brain diseases, their diagnosis and treatment. In all these areas, molecular science has advanced our understanding. This multi-disciplinary review combines viewpoints from laboratory science, clinical medicine and the bioscience industry. First, we review the advances that molecular science has brought to brain health in the past twenty years. These include therapeutic antibodies for CNS diseases (multiple sclerosis, Alzheimer disease) and the dramatic introduction of RNA-targeted therapeutics. Second, we highlight areas where greater molecular understanding is needed. Salient examples are the relation of brain structure to cognitive symptoms, and molecular biomarkers for diagnosis, target discovery and testing of interventions. Finally, we speculate on aspects of molecular science that are likely to advance brain health in the next twenty years. These include: cell senescence and chronobiology; gene editing (notably, CRISPR) and RNA targeting (RNA interference, miRNA manipulation); brain-immune interactions; novel drug targets (AQP4, HIF1, Toll-like receptors); and novel chemistry to make new drugs (molecular machines, quantum molecular modelling and "click" chemistry). Early testing of the relationships between molecular pathways and clinical manifestations will drive much-needed breakthroughs in neurology and psychiatry., Competing Interests: Hainsworth leads MRC-Dementias Platform UK Vascular Experimental Medicine group and was Chief Investigator on the PASTIS trial. He has received honoraria from Eli Lilly and NIA and serves as a scientific consultant for Aribio Inc. Blackburn is a Non-Executive Board Member of Umecrine Cognition AB. Bradshaw holds a role within ISTAART Immunity and Neurodegeneration PIA and is a Founder of IMAD Therapeutics. Isaacs was Principal Investigator on the PASTIS trial. He has been a PI on clinical trials funded by Roche, Merck and Lupin Pharmaceuticals and has received funds from Nestle, Biogen and Roche. All other authors report no conflicts of Interest related to this manuscript. All the claims stated here come from the various authors’ personal opinions and reflections. The text in this article is in no sense official or legally binding., (© 2024 The Authors. Published by Elsevier B.V.)

Competing Interests: Conflicts of interest None to declare.

Competing Interests: Competing interests: None declared.

Cryptococcus neoformans, Cryptococcus gattii and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response to C. albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C. neoformans, C. gattii and C. albicans infection of peripheral blood mononuclear cells (PBMCs) collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C. albicans and unique expression signatures from all three fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Global and trichoscopic photography are fundamental in the clinical assessment of hair loss. Standardised protocols in this respect are lacking., Objectives: To create novel, pragmatic and flexible standardised photography protocols for hair loss, which are practical to use for clinicians and medical photographers alike., Methods: Published disease severity scales for a variety of hair loss conditions were utilised to create standardised photography protocols. There were reviewed and refined by a national clinical working group of consultant dermatologists specialising in hair loss., Results: Three main presentation-based protocols are presented, defined by the type of hair loss a patient may present with; including pattern loss, frontal fibrosing alopecia/traction alopecia and alopecia areata and other patchy hair loss disorders. Additional supplementary protocols facilitate further specific views for a variety of individualised clinical scenarios, based on user discretion., Conclusions: We present novel, pragmatic, standardised photography protocols for hair loss disorders. These can be used by clinicians even where formal medical photography units are unavailable. Standardisation allows high-quality, informative images for objective assessment and monitoring of hair loss in clinical practice, as well as in research settings., (© 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.)

Background: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown., Methods: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis., Results: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup., Conclusions: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664., Competing Interests: Dr Lampert reports honoraria and research support from Medtronic, Abbott-St. Jude, and Boston Scientific, as well as serving on the Advisory Board for Medtronic. Dr Day received consulting and grant funding from Lexicon Pharmaceuticals, grant funding from Bristol Myers Squibb, and DMC from Cytokinetics. L. Salberg consulted for Biomarin. Dr Tome Esteban consulted for BMS and Cytokinetics. Dr Abrams served on the Scientific Advisory Board for Thryv Therapeutics and consulted for Rocket Pharmaceuticals. Dr Aziz served on the Medtronic Advisory Committee. Dr Behr consulted for Boston Scientific. Dr Berul received research funding from Medtronic. Dr Cerrone provided teaching and CME activities for Abbott and Medtronic. Dr Erickson received funding from Integer. Dr Estes reports consulting for Boston Scientific and Medtronic. Dr Ethridge reports funding from Spauling Research (ECG reading) and UpToDate. Dr James was a consultant for Pfizer and Lexeo Therapeutics and received research funding from Lexeo Therapeutics and StrideBio. Dr Law was a consultant for Medtronic and St. Jude and a speaker for Boston Scientific. Dr Olshansky, AstraZeneca DSMB (Data Safety Monitoring Board). Dr Noseworthy and Mayo Clinic have filed patents related to the application of artificial intelligence to the ECG for diagnosis and risk stratification and have licensed several A-ECG algorithms to Anumana. Dr Noseworthy and Mayo Clinic have a relationship with AliveCor related to the measurement of the QT interval on the Kardia device. Dr Shah was a consultant for Medtronic and Tenaya. Dr Ware received research support and/or consultancy fees from MyoKardia, Bristol Myers Squibb, Foresite Labs, Pfizer, and Health Lumen. Dr Ware is supported by Medical Research Council (UK), British Heart Foundation (RE/18/4/34215), and the NIHR Imperial College Biomedical Research Centre. Dr Ackerman has served as a consultant for Abbott, BioMarin Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Illumina, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. The other authors report no conflicts.

Aims and Method: The aim of this project was to set out recommendations for the section 17 leave form to reflect guidance provided in the Mental Health Act 1983: Code of Practice, following local Care Quality Commission feedback. We reviewed guidance in the Code and publicly available leave forms to identify items to include in the leave form. Then, we determined which publicly available leave forms included each item and reviewed whether the item should be included in the leave form and whether any reformulation was needed., Results: Using the method described, we identified a list of items that should be included in the leave form. When comparing the leave forms of different trusts, there was considerable variation with respect to which items were included in each form., Clinical Implications: We provide some recommendations for future practice regarding section 17 leave forms to facilitate consistency with the Code and between different trusts.

Objectives: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins., Design: Qualitative semi-structured interviews with parents and clinicians. Data were analysed using reflexive thematic analysis and considered against the Principles of Biomedical Ethics., Participants and Setting: We interviewed 19 UK parents experiencing (six mothers, two partners) or had recently experienced (eight mothers, three partners) early-onset sFGR in MC twin pregnancy and 14 specialist clinicians from the UK and Europe., Results: Participants viewed the proposed RCT as 'ethically murky' because they believed that the management of sFGR in MC twin pregnancy should be individualised according to the type and severity of sFGR. Clinicians prioritised the gestational age, size, decrease in growth velocity, access to the placental vessels and acceptability of intervention for parents. Discussions and decision-making about selective termination appeared to cause long-term harm (maleficence). The most important outcome for parents and clinicians was 'live birth'. For clinicians, this was the live birth of at least one twin. For parents, this meant the live birth of both twins, even if this meant that their babies had neurodevelopmental impairment or disabilities., Conclusions: All three pregnancy management approaches for sFGR in MC twin pregnancy carry risks and benefits, and the ultimate goal for parents is to receive individualised care to achieve the best possible outcome for both twins. An RCT was not acceptable to parents or clinicians or seen as ethically appropriate. Alternative study designs should be considered to answer this important research question., Competing Interests: Competing interests: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme grant payments were made to the institutions of all authors (except REA, NF and SL). TKM and MP employment roles were funded by the NIHR HTA programme grant payment made to their institution., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aims: Our primary aim was to establish the proportion of female orthopaedic consultants who perform arthroplasty via cases submitted to the National Joint Registry (NJR), which covers England, Wales, Northern Ireland, the Isle of Man, and Guernsey. Secondary aims included comparing time since specialist registration, private practice participation, and number of hospitals worked in between male and female surgeons., Methods: Publicly available data from the NJR was extracted on the types of arthroplasty performed by each surgeon, and the number of procedures of each type undertaken. Each surgeon was cross-referenced with the General Medical Council (GMC) website, using GMC number to extract surgeon demographic data. These included sex, region of practice, and dates of full and specialist registration., Results: Of 2,895 surgeons contributing to the NJR in 2023, 102 (4%) were female. The highest proportions of female surgeons were among those who performed elbow (n = 25; 5%), shoulder (n = 24; 4%), and ankle (n = 8; 4%) arthroplasty. Hip (n = 66; 3%) and knee arthroplasty (n = 39; 2%) had the lowest female representation. Female surgeons had been practising for a median of 10.4 years since specialist registration compared to 13.7 years for males (p < 0.001). Northern Ireland was the region with the highest proportion of female arthroplasty surgeons (8%). A greater proportion of male surgeons worked in private practice (63% vs 24%; p < 0.001) and in multiple hospitals (74% vs 40%; p < 0.001)., Conclusion: Only 4% of surgeons currently contributing cases to the NJR are female, with the highest proportion performing elbow arthroplasty (5%). Female orthopaedic surgeons in the NJR are earlier in their careers than male surgeons, and are less involved in private practice. There is a wide geographical variation in the proportion of female arthroplasty surgeons., Competing Interests: C. B. Hing reports that the editorial stipend for The Knee for Elsevier is unrelated to this work. C. E. H. Scott declares a department grant and payment for education delivery from Stryker; consulting fees from Stryker, Smith & Nephew, and Osstec; being on the data safety monitoring board for the PASHION trial; and being a board member of The Bone & Joint Journal, all of which are also unrelated to this paper., (© 2024 Abelleyra Lastoria et al.)

Background: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes., Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data., Design: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis., Participants: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies)., Predictors: Maternal clinical characteristics, biochemical and ultrasound markers., Primary Outcomes: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight., Analysis: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance ( c -statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ 2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model., Results: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c -statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g)., Limitations: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data., Future Work: International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation., Conclusion: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management., Study Registration: This study is registered as PROSPERO CRD42019135045., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment ; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation., Competing Interests: Disclosure The author is a member of the European Association of Urology and the American Society of Clinical Oncology penile cancer guidelines panel and also a Trustee to Orchid, a male cancer charity that supports men with penile cancer. The author has received an honorarium for consultation and lectures on bladder cancer for Olympus, Cepheid, and Kyowa Kirin., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors., Study Design: This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age., Results: 72 pregnancies with SGA were first evaluated at median (IQR) of 28 +5 (26 +2 -31 +3 ) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07-0.36 vs 0.32, 95 % IQR: 0.20-0.53, p = 0.008) and 0.26, 95 % CI: 0.16-0.55 vs 0.43, 95 % IQR: 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80-7.30 vs 1.74, 95 % IQR:1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27-3.07 vs 0.17, 95 % IQR: 0.08-0.43, p = 0.022)., Conclusion: These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR., 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 Elsevier B.V. All rights reserved.)

Objective: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and prevalence of placentally derived composite of adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO-S)., Methods: This was a single-center retrospective cohort study of data obtained in a tertiary maternity unit. Data regarding ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation) were collected for 13 165 singleton pregnancies screened routinely in the first trimester for pre-eclampsia using the Fetal Medicine Foundation combined risk-assessment algorithm. CAPO was defined as the presence of one or more interrelated outcomes associated with placental dysfunction, namely, hypertensive disorders of pregnancy, preterm birth, birth weight ≤ 10 th centile and stillbirth. CAPO-S was defined as the presence of one or more of the following: hypertensive disorders of pregnancy at < 37 + 0 weeks, preterm birth at < 34 + 0 weeks, birth weight ≤ 5 th centile and stillbirth at < 37 + 0 weeks., Results: The prevalence of CAPO was 16.3% in white women, 29.3% in black women and 29.3% in South Asian women. However, half (51.7%) of all CAPO cases occurred in white women. There was a strong interaction between ethnicity and socioeconomic deprivation, with a correlation coefficient of -0.223. Both ethnicity and socioeconomic deprivation influenced the prevalence of CAPO and CAPO-S, with the contribution of ethnicity being the strongest., Conclusions: Black and Asian ethnicity, as well as socioeconomic deprivation, influence the prevalence of placenta-mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in white women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placenta-mediated CAPO. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide., Main Text: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates., Conclusion: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities., (© 2024 European Society of Cardiology.)

Purpose: Maxillary sinus carcinomas usually present as a locally advanced disease at the time of diagnosis and it is extremely unusual to have a second primary maxillary carcinoma on the contralateral side after many years of completion of treatment of the first malignancy. We present here a case report of a sphenopalatine artery (SPA) pseudoaneurysm mimicking the second primary maxillary carcinoma., Methods: We reviewed the literature for SPA pseudoaneurysm., Results/case Report: This report describes the case of a 90-year-old man with a background of adenoid cystic carcinoma of the right maxillary sinus, diagnosed and treated with surgery and radiotherapy 14 years ago, who presented with a history of multiple episodes of epistaxis. The radiological evaluation showed a heterogeneously enhancing mass with a central hemorrhagic component and surrounding bony erosions in the left maxillary sinus and the patient was planned for biopsy from the suspicious mass along with SPA ligation. However, on opening the maxillary antrum there was excessive bleeding and it was determined unsafe to proceed further. The patient was subsequently taken to interventional radiology for diagnostic angiography which revealed an SPA pseudoaneurysm that was subsequently embolized successfully., Conclusions: Sphenopalatine artery pseudoaneurysms should be considered as a differential for recurrent epistaxis in patients with a history of sinonasal malignancy. In such cases, endovascular embolization is a viable management option., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways., Methods: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed., Results: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified., Conclusion: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes., Competing Interests: Declaration of competing interest There are no conflicts of interest. This research was funded by Instituto de Salud Carlos III (ISCIII) (grant number PI22/00705). All patients signed the informed consent (local Ethical Committee approval CEImPA 2022.254)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The environmental impact of healthcare is an issue currently examined with increased scrutiny and on a global scale with multiple stakeholders seeking to identify the appropriate interventions to reduce it. Interestingly, a significant portion of healthcare's environmental impact stems from intensive modalities of treatment for chronic disease. There is no better example than End-Stage Renal Disease (ESRD), where dialysis or transplantation are the modalities of treatment offered to the vast majority of these patients. Kidney transplantation (KTx) offers a longer life expectancy and improved quality of life in comparison to dialysis. Cost-effectiveness analyses have proven its financial superiority, as well. PubMed and EMBASE literature search using keywords "kidney transplantation", "carbon footprint", "sustainability" showed that there is no published work in the field of environmental sustainability in kidney transplantation. Relevant literature was identified for surgical services and applied to transplantation. Assuming its environmental superiority to dialysis, maximising KTx rate would be an important action towards "green" renal care services. That could be achieved through living organ donation, systematic use of machine perfusion for extended criteria deceased donors and individualised immune risk stratification techniques. All these measures aim towards implementing enhanced recovery protocols and two vital steps can be taken towards assessing their value. The first step is a detailed audit of the environmental impact of these novel techniques and secondly their impact in reducing the length of hospital stay and its subsequent environmental impact. Another key element is delivering appropriate post-operative care, substituting allograft biopsy with non-invasive techniques and reducing physical outpatient follow-up, using telemedicine. The gap in quantifying KTx services environmental impact needs to be addressed urgently, with development of strategies within the multidisciplinary transplant team. Introducing novel technologies can lead to donor pool expansion and improved organ utilisation rates, transforming transplant services in "green" hubs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: Circulating histones are released by extensive tissue injury or cell death and play important pathogenic roles in critical illnesses. Their interaction with circulating plasma components and the potential roles in the clinical setting are not fully understood., Objectives: We aimed to characterize the interaction of histones with fibrinogen and explore its roles in vitro, in vivo, and in patient samples., Methods: Histone-fibrinogen binding was assessed by electrophoresis and enzyme-linked immunosorbent assay-based affinity assay. Functional significance was explored using washed platelets and endothelial cells in vitro and histone-infusion mouse models in vivo. To determine clinical translatability, a retrospective single-center cohort study was conducted on patients requiring intensive care admission (n = 199) and validated in a cohort of hospitalized patients with COVID-19 (n = 69)., Results: Fibrinogen binds histones through its D-domain with high affinity (calf thymus histones, K D  = 18.0 ± 5.6 nM; histone 3, K D  = 2.7 ± 0.8 nM; and histone 4, K D  = 2.0 ± 0.7 nM) and significantly reduces histone-induced endothelial damage and platelet aggregation in vitro and in vivo in a histone-infusion mouse model. Physiologic concentrations of fibrinogen can neutralize low levels of circulating histones and increase the cytotoxicity threshold of histones to 50 μg/mL. In a cohort of patients requiring intensive care, a histone:fibrinogen ratio of ≥6 on admission was associated with moderate-severe thrombocytopenia and independently predicted mortality. This finding was validated in a cohort of hospitalized patients with COVID-19., Conclusion: Fibrinogen buffers the cytotoxic properties of circulating histones. Detection and monitoring of circulating histones and histone:fibrinogen ratios will help identify critically ill patients at highest risk of adverse outcomes who might benefit from antihistone therapy., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)