Transcriptome analysis of Burkitt lymphoma cells treated with anti-convulsant drugs that are inhibitors of Epstein-Barr virus lytic reactivation.

Herpesviruses have two distinct life cycle stages, latency and lytic replication. Epstein-Barr virus (EBV), a gamma-herpesvirus, establishes latency in vivo and in cultured cells. Cell lines harboring latent EBV can be induced into the lytic cycle by treatment with chemical inducing agents. In the Burkitt lymphoma cell line HH514-16 the viral lytic cycle is triggered by butyrate, a histone deacetylase (HDAC) inhibitor. Butyrate also alters expression of thousands of cellular genes. However, valproic acid (VPA), another HDAC inhibitor with global effects on cellular gene expression blocks EBV lytic gene expression in Burkitt lymphoma cell lines. Valpromide (VPM), an amide derivative of VPA, is not an HDAC inhibitor, but like VPA blocks induction of the EBV lytic cycle. VPA and VPM are the first examples of inhibitors of initial stages of lytic reactivation. We compared the effects of VPA and VPM, alone and in combination with butyrate, on host cellular gene expression using whole transcriptome analysis (RNA-seq). Gene expression was analyzed 6 h after addition of the compounds, a time before the first EBV lytic transcripts are detected. The results address two alternative, yet possibly complementary, mechanisms for regulation of EBV lytic reactivation. First, cellular genes that were up- or down-regulated by butyrate, but no longer altered in the presence of VPA or VPM, represent genes that correlated with EBV lytic reactivation. Second, genes regulated similarly by VPA and VPM in the absence and presence of butyrate are candidates for suppressors of EBV reactivation. Two genes upregulated by the lytic cycle inhibitors, CHAC1 and SLC7A11, are related to redox status and the iron-dependent cell death pathway ferroptosis. This study generates new hypotheses for control of the latency to lytic cycle switch of EBV and provides the first description of effects of the anti-convulsant drug VPM on global human cellular gene expression.

Delivering medical leadership training through the Healthcare Leadership Academy: a four year analysis.

BACKGROUND: Formal leadership training is typically targeted at senior health professionals. The Healthcare Leadership Academy (HLA) was formed in 2016 to provide a leadership programme for students and early-career health professionals. This study analyses the effectiveness of the HLA scholarship programme as an intervention for improving interest in and preparing scholars for future leadership roles. METHODS: Survey data was used to assess the effectiveness of the HLA Scholarship program in cultivating leadership development. Questions required either multiple-choice, free text, ranking or Likert scale ('strongly agree', 'agree', 'neither agree nor disagree', 'disagree', 'strongly disagree) responses. Participants spanned six regions (London, Newcastle, Bristol, Belfast, Edinburgh, and Amsterdam) in four countries (England, Scotland, Northern Ireland, and the Netherlands). Descriptive statistical analyses were conducted, and insights were drawn from the open-ended survey questions using a leadership framework. RESULTS: Seventy participants who underwent the course between 2016 and 2020 completed the questionnaire. Nearly all (99%) found that the training provided on the programme had equipped them to be more effective leaders, with 86% of respondents stating that they were more likely to take on leadership roles. Nearly all (97.1%) found the course to be either of good or very good quality. Nineteen insights were identified from free text responses that fitted under one of the four themes of the leadership framework: "optimising", "resolving uncertainty", "enhancing adaptability", and "promulgating a vision". CONCLUSIONS: Healthcare leadership is a non-negotiable component of healthcare delivery in the 21st Century. As healthcare professionals, it is our duty to be effective leaders confident and competent in navigating the increasingly complex systems within which we operate for the benefit of ourselves, colleagues, and patients. By accounting for known shortcomings and developing ameliorative measures, the HLA Scholarship programme addresses unmet needs in a structured manner to support effective long-term healthcare leadership development.

Autologous breast reconstruction in low- and middle-income countries (LMICs): a systematic review of current practices and challenges.

INTRODUCTION: Efforts to improve global healthcare persist, yet LMICs face challenges accessing surgical care, especially breast reconstruction amidst rising breast cancer cases. This review evaluates the present state and challenges of autologous breast reconstruction in low- and middle-income countries (LMICs). EVIDENCE ACQUISITION: Utilizing the PRISMA guidelines and the Cochrane Collaboration's standards, databases such as EMBASE, MEDLINE, Cochrane, PubMed, and Google Scholar were examined for studies on breast reconstruction in LMICs (based on the World Bank's 2022-2023 definitions) up to August 2022. Articles and case reports focusing on autologous reconstruction following breast cancer surgery in these regions were incorporated. EVIDENCE SYNTHESIS: From an initial 288 articles, 19 met the criteria after thorough assessment. These articles documented 4899 patient cases from LMICs, with the breakdown being: 11 on LD flaps, nine on TRAM flaps, eight on DIEP flaps, two on TDAP flaps, and one on TMG flap. Flap necrosis emerged as the prevalent complication in four studies. CONCLUSIONS: While autologous breast reconstruction presents superior aesthetic benefits without notable long-term economic setbacks, its adoption in LMICs is limited. This is partly due to the domination of implant-based methods among patients and surgeons, selected due to convenience. The scarcity of concrete evidence and standardized metrics in LMICs clouds the understanding of this procedure. Despite its advantages, awareness is low, necessitating more training and awareness campaigns. Uniform reporting, quality data, and financial analysis can provide a comprehensive LMIC understanding, aiding future research.

Surgeon views regarding the adoption of a novel surgical innovation into clinical practice: systematic review.

BACKGROUND: The haphazard adoption of new surgical technologies into practice has the potential to cause patient harm and there are many misconceptions in the decision-making behind the adoption of new innovations. The aim of this study was to synthesize factors affecting a surgeon's decision to adopt a novel surgical innovation into clinical practice. METHODS: A systematic literature search was performed to obtain all studies where surgeon views on the adoption of a novel surgical innovation into clinical practice have been collected. The databases screened were MEDLINE, Embase, Science Direct, Scopus, the Web of Science, and the Cochrane Library of Systematic Reviews (last accessed October 2022). Innovations covered multiple specialties, including cardiac, general, urology, and orthopaedics. The quality of the papers was assessed using a 10-question Critical Appraisal Skills Programme (CASP) tool for qualitative research. RESULTS: A total of 26 studies (including 1112 participants, of which 694 were surgeons) from nine countries satisfied the inclusion and exclusion criteria. Types of study included semi-structured interviews and focus groups, for example. Themes and sub-themes that emerged after a thematic synthesis were categorized using five causal factors (structural, organizational, patient-level, provider-level, and innovation-based). These themes were further split into facilitators and barriers. Key facilitators to adoption of an innovation include improved clinical outcomes, cost-effectiveness, and support from internal and external stakeholders. Barriers to adoption include lack of organizational support and views of senior surgeons. CONCLUSION: There are multiple complex factors that dynamically interact, affecting the adoption of a novel surgical innovation into clinical practice. There is a need to further investigate surgeon and other stakeholder views regarding the strength of clinical evidence required to support the widespread adoption of a surgical innovation into clinical practice.

The Current Status and Challenges of Prehospital Trauma Care in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: This review aims to understand the present circumstances on the provision of prehospital trauma care in low- and middle-income countries (LMICs), particularly scoping the challenges experienced by LMICs in this regard. The objective is to systematically evaluate the currently available evidence on this topic. Based on the themes and challenges identified in the provision of prehospital trauma care in LMICs, we provide a series of recommendations and a knowledge base for future research in the field. METHODS: A systematic database search was conducted of original articles that explored and reported on prehospital trauma care in LMIC in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to March 2022. All original articles reporting on prehospital trauma care from 2010 to 2022 in LMICs were assessed, excluding case reports, small case series, editorials, abstracts, and pre-clinical studies; those with data inconsistencies that impede data extraction; and those with study populations fewer than ten. RESULTS: The literature search identified 2,128 articles, of which 29 were included in this review, featuring 27,848 participants from LMICs countries. Four main areas of focus within the studies were identified: (1) exploring emergency service systems, frameworks, and interconnected networks within the context of prehospital trauma care; (2) transportation of patients from the response site to hospital care; (3) medical education and the effects of first responder training in LMICs; and (4) cultural and social factors influencing prehospital trauma care-seeking behaviors. Due to overarching gaps in social and health care systems, significant barriers exist at various stages of providing prehospital trauma care in LMICs, particularly in injury identification, seeking treatment, transportation to hospital, and receiving timely treatment and post-intervention support. CONCLUSION: The provision of prehospital trauma care in LMICs faces significant barriers at multiple levels, largely dependent on wider social, geographic, economic, and political factors impeding the development of such higher functioning systems within health care. However, there have been numerous breakthroughs within certain LMICs in different aspects of prehospital trauma care, supported to varying degrees by international initiatives, that serve as case studies for widespread implementation and targets. Such experiential learning is essential due to the heterogenous landscapes that comprise LMICs.

Machine learning algorithms for the prognostication of abdominal aortic aneurysm progression: a systematic review.

INTRODUCTION: Abdominal aortic aneurysm (AAA), often characterized by an abdominal aortic diameter over 3.0 cm, is managed through screening, surveillance, and surgical intervention. AAA growth can be heterogeneous and rupture carries a high mortality rate, with size and certain risk factors influencing rupture risk. Research is ongoing to accurately predict individual AAA growth rates for personalized management. Machine learning, a subset of artificial intelligence, has shown promise in various medical fields, including endoleak detection post-EVAR. However, its application for predicting AAA growth remains insufficiently explored, thus necessitating further investigation. Subsequently, this paper aims to summarize the current status of machine learning in predicting AAA growth. EVIDENCE ACQUISITION: A systematic database search of Embase, MEDLINE, Cochrane, PubMed and Google Scholar from inception till December 2022 was conducted of original articles that discussed the use of machine learning in predicting AAA growth using the aforementioned databases. EVIDENCE SYNTHESIS: Overall, 2742 articles were extracted, of which seven retrospective studies involving 410 patients were included using a predetermined criteria. Six out of seven studies applied a supervised learning approach for their machine learning (ML) models, with considerable diversity observed within specific ML models. The majority of the studies concluded that machine learning models perform better in predicting AAA growth in comparison to reference models. All studies focused on predicting AAA growth over specified durations. Maximal luminal diameter was the most frequently used indicator, with alternative predictors being AAA volume, ILT (intraluminal thrombus) and flow-medicated diameter (FMD). CONCLUSIONS: The nascent field of applying machine learning (ML) for Abdominal Aortic Aneurysm (AAA) expansion prediction exhibits potential to enhance predictive accuracy across diverse parameters. Future studies must emphasize evidencing clinical utility in a healthcare system context, thereby ensuring patient outcome improvement. This will necessitate addressing key ethical implications in establishing prospective studies related to this topic and collaboration among pivotal stakeholders within the AI field.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report.

BACKGROUND: Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV. CASE: Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash. CONCLUSION: In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.

Removing Michigan's Lead Water Service Lines: Economic Savings, Health Benefits, And Improved Health Equity.

Michigan's recently revised Lead and Copper Rule requires water utilities to inventory existing water service lines by 2025 and replace all lead-containing lines by 2041. This article summarizes a cost-benefit analysis using new inventory data on the number of lead service lines in the state, the projected cost of their replacement, and the estimated lifetime benefits from reduced lead exposure. Replacing 423,479 lead service lines would reduce lead exposure for 420,800 newborns and result in $3.24 billion in future benefits (compared with replacement costs of $1.33 billion). This would generate net savings of $1.91 billion and a societal return on investment of $2.44 per dollar invested. These estimates are conservative and include only quantified benefits for newborn children in Michigan for the period 2020-60. More than 153,100 of the children benefiting would be non-White (of whom 78,400 would be Black or African American), and 106,900 would be in households with incomes below the federal poverty level. Sensitivity analyses show that accelerating the replacement pace would increase the societal return on investment. This primary prevention-driven policy has the potential to reduce childhood lead exposure and improve health equity.

Comparative Clinical Performances of Tunneled Central Venous Catheters versus Arterio-Venous Accesses in Patients Receiving High-Volume Hemodiafiltration: The Case for High-Flow DualCath, a Tunneled Two-Single-Lumen Silicone Catheter.

Tunneled central venous catheters (CVC) are mainly considered as a rescue vascular access option in dialysis but are still used on approximately one quarter of prevalent patients worldwide even though they are associated with poor performances and higher risks. STUDY DESIGN: in this retrospective single-center study, we aimed to report on the clinical performances achieved with high-flow tunneled CVCs (DualCath or DCath) and compared them with arteriovenous accesses (AVAs, e.g., AV fistula, AV graft, and Thomas Shunt) in a hospital-based dialysis unit. METHODS: Sixty-eight stage 5 chronic kidney disease dialysis-dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up with for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-ups of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V, total Kt, ultrafiltration volume, and percent reduction in ß2-M were measured monthly as part of quality control in our unit. RESULTS: At baseline, the effective blood flow using a DCath was close to 400 mL/min, similar to an AVA. Recirculation with a DCath (7%, 6-13%) was higher than with an AVA. The diffusive dialysis dose delivered with a DCath (spKt and eKt/V) and convective dialysis dose achieved with a DCath were slightly lower than those achieved with AVAs, but they were still much higher than is recommended by guidelines. The percent reduction in ß2-M achieved with a DCath was also 4 to 10% lower than that achieved with an AVA. On longitudinal follow-up, the main clinical performance indicators of DCaths (total Kt and total ultrafiltration volume, L/session) were maintained as very stable over time and close to those achieved with AVAs. CONCLUSIONS: As shown in this study, high-flow DualCath tunneled two-single-lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performance. These results relied on the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Leading Transformation in Medical Education Through Extended Reality.

Extended reality (XR) has exponentially developed over the past decades to incorporate technology whereby users can visualise, explore, and interact with 3-dimensional-generated computer environments, and superimpose virtual reality (VR) onto real-world environments, thus displaying information and data on various levels of the reality-virtuality continuum. In the context of medicine, VR tools allow for anatomical assessment and diagnosis, surgical training through lifelike procedural simulations, planning of surgeries and biopsies, intraprocedural guidance, and medical education. The following chapter aims to provide an overview of the currently available evidence and perspectives on the application of XR within medical education. It will focus on undergraduate and postgraduate teaching, medical education within Low-Middle Income Countries, key practical steps in implementing a successful XR programme, and the limitations and future of extended reality within medical education.

Visualisation Approaches in Technology-Enhanced Medical Simulation Learning: Current Evidence and Future Directions.

Technology-enhanced learning (TEL) has been proposed as an approach to minimise the healthcare workforce shortage preventing universal healthcare coverage. Simulation-based medical education is a well-established teaching method. Little is known about effective strategies to translate in-person medical simulation teaching into a virtual world. This work aimed to review the literature on approaches to visualisation in technology-enhanced medical simulation. A systematic search strategy was optimised using three databases: Embase, MEDLINE, and APA PsycInfo. Additional papers were identified through cross-referencing. The last date of this search was 3 January 2022. The articles were analysed qualitatively. The risk of bias was assessed using ROBINS-I and RoB 2 tools. The search yielded 656 results with 9 additional papers identified through cross-referencing. Following deduplication and exclusions, 23 articles were included in a qualitative synthesis of evidence. Offline and online computer-based modules with virtual patient cases or practical skills simulations were identified as the most prevalent clinical simulation teaching modalities. Visualisation approaches included text, images, animations, videos, and 3D environments. Significant heterogeneity of study designs with a moderate risk of bias was established. Based on the current data, the virtual patient scenarios should use natural language input interfaces enriched with video and voice recordings, 3D animations, and short text descriptions to make the patient management experience more lifelike and increase knowledge retention. However, there is no agreed framework for assessing the pedagogical value of these innovations. High-quality randomised controlled trials of TEL-based clinical simulation are essential to advance the field.

Efficacy of pharmacological and mechanical cervical priming methods for induction of labour and their applicability for outpatient management: A systematic review of randomised controlled trials.

BACKGROUND: A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods are available to achieve cervical ripening prior to induction of labour (IOL). In this systematic review, we will report the literature to date, and investigate the efficacy and safety of using the Foley catheter balloon or prostaglandins for cervical ripening, comparing both methods with each other, and discuss the implications of these findings for midwifery led units. METHODS: English peer-reviewed journals were systematically searched in the databases PubMed, MEDLINE, EMCARE, EMBASE and CINAHL, for studies investigating cervical ripening using the FC or PGs. Additional randomised controlled trials (RCTs) and non-RCTs were identified by a manual search. Search terms included: cervix dilatation effacement, cervix ripening, outpatient, ambulatory care, obstetric patients, pharmacological preparations, and Foley catheter. Only RCTs of FC versus PG or either intervention versus placebo or intervention in the in-patient Vs. outpatient setting were included. 15 RCTs were included. RESULTS: The results of this review show that both FC and PG analogues are equally effective cervical ripening agents. When compared to FC, PGs lead to a reduced requirement for oxytocin augmentation and a shorter intervention to delivery interval. However, PG use is also associated with an increased risk of hyperstimulation, cardiotocographic monitoring abnormalities and negative neonatal outcomes. CONCLUSIONS: FC cervical ripening is an effective method of outpatient cervical priming, which is safe, acceptable, and cost-effective and thus has a potential role in both resource-rich and resource-poor countries. With appropriate dosing, some PG analogues also appear to offer similar outcomes.

Pregnant theatre staff in orthopaedic operating rooms: An observational study.

PURPOSE: Trauma & Orthopaedic (T&O) surgery presents several occupational hazards to pregnant women and the unborn child. National bodies have produced guidelines to mitigate these risks as far as possible but individual trusts must be aware of them and implement them in their local policies. Our study aims to re-assess whether national guidelines for the protection of pregnant women are better adhered to nationally by providing a comparison to a previous study in 2018. METHODS: A national observational study of 146 NHS trusts in the UK was conducted. Each trust was asked to complete a freedom of information request regarding all orthopaedic guidelines relating to pregnant theatre staff, which specifically related to the protection of the mother and foetus from exposure to harmful activity in theatre. Compliance was ascertained by cross-checking local policies with national guidelines. RESULTS: 82/146 (52.0%) of NHS trusts responded to the Freedom of Information  request. 31/75 (41.3%) respondents followed Health and Safety Executive (HSE) guidance for New and Expectant Mothers with 17/75 (22.7%) following multiple national guidelines. 16/75 (21.3%) NHS trusts do not follow any national guidelines in protecting new and expectant mothers from occupational hazards in the orthopaedic theatre setting. CONCLUSIONS: Although an improvement has been made since 2018 in complying with national guidelines protecting new and expectant mothers from orthopaedic-related hazards, a sizeable proportion of NHS trusts do not comply with any national guidelines, putting employees at undue risk. There is a continued need for pregnant surgeons to be aware of and seek occupational health advice from dedicated professional bodies if the NHS trust does not provide specific guidance. Simultaneously, a sustained effort must be present to continue to inform NHS employers of their duty to protect new and expectant mothers and signpost them to relevant guidance.

Mitral valve surgery assisted by virtual and augmented reality: Cardiac surgery at the front of innovation.

BACKGROUND: Given the variety in mitral valve (MV) pathology and associated surgical techniques, extended reality (XR) holds great potential to assist MV surgeons. This review aims to systematically evaluate the currently available evidence investigating the use of XR and associated technologies in MV surgery. METHODS: A systematic database search was conducted of original articles and case reports that explored the use of XR and MV surgery in EMBASE, MEDLINE, Cochrane database and Google Scholar, from inception to February 2022. RESULTS: Our search yielded 171 articles, of which 15 studies were included in this review, featuring 328 patients. Two main areas of application were identified: (i) pre-operative planning and (ii) predicting post-operative outcomes. The articles reporting outcomes relating to pre-operative planning were further categorised as exploring themes relevant to (i) mitral annular assessment; (ii) training; (iii) evaluation of surgical technique; (iv) surgical approach or plan and (v) selecting ring size or type. Preoperatively, XR has been shown to evaluate mitral annular pathology more accurately than echocardiography, informing the surgeon about the optimal surgical technique, approach and plan for a particular patient's MV pathology. Furthermore, XR could simulate and aid ring size/type selection for MV annuloplasty, creating a personalized surgical plan. Additionally, XR could estimate the postoperative MV biomechanical and physiological characteristics, predicting and pre-empting post-operative complications. CONCLUSION: XR demonstrated promising applications for assisting MV surgery, enhancing outcomes and patient-centred care, nevertheless, there remain the need for randomized studies to ascertain its feasibility, safety, and validity in clinical practice.