Prevalence of undiagnosed stage B heart failure among emergency department patients.

INTRODUCTION: Heart failure (HF) is associated with significant morbidity, mortality, and health care costs. Stage B HF is defined as structural heart disease prior to developing symptomatic HF. If identified early in the disease process, preventative measures may be implemented to slow disease progression to Stage C (symptomatic) or Stage D (refractory) HF. Previous research has focused on outpatient screening for HF in the primary care setting; however, there are limited data on Stage B HF screening in the Emergency Department (ED) setting. The objective of this study was to determine the prevalence of undiagnosed Stage B HF among those with cardiovascular risk factors in the ED setting and identify which risk factors were associated with a greater risk of having Stage B HF. METHODS: A prospective, observational study was performed in a single, urban academic ED from 07/2023 to 05/2024. Inclusion criteria were age ≥ 45 years with hypertension, diabetes, obesity, coronary heart disease, previous cardiotoxic chemotherapy, or family history of HF. Exclusion criteria included signs or symptoms of HF, known history of HF, valvular disease, current atrial fibrillation, or primary language other than English. A focused cardiac ultrasound was performed and interpreted by ultrasound-fellowship trained emergency physicians. Sonographers assessed systolic function as ejection fraction <50 % using visual assessment in at least two different views. Sonographers assessed diastolic dysfunction as an E/A ratio < 0.8, or if ≥2 of the following were present: septal e' < 7 cm/s or lateral e' < 10 cm/s, E/e' ratio > 14, or left atrial volume > 34 mL/m2. Descriptive statistics were performed, followed by comparative analyses and regression modeling. RESULTS: 209 participants were included in the study, with a mean age of 60 years and 51.7 % women. Of these, 125 (59.8 %) had undiagnosed Stage B HF, with 13 (10.4 %) having systolic dysfunction and 112 (89.6 %) having isolated diastolic dysfunction. Among those with isolated diastolic dysfunction, 44 (39.3 %) were grade I, 66 (58.9 %) were grade II, and 2 (1.8 %) were grade III. Predictors of undiagnosed Stage B HF included age (odds ratio 1.06; 95 % CI 1.02 to 1.10) and BMI (odds ratio 1.06; 95 % CI 1.01 to 1.10). CONCLUSION: A large majority of ED patients with cardiovascular risk factors had undiagnosed Stage B HF. Age and obesity were associated with a higher risk of Stage B HF. This provides an opportunity for early identification and intervention for patients with undiagnosed Stage B HF to reduce progression to more severe HF.

Real-world implementation of the Copenhagen Adduction Exercise: what do football teams modify and why?

Objectives: To evaluate the use and modification of the Copenhagen Adduction Exercise in football (soccer) teams, including the reasons for modification and alternate injury-prevention strategies. Methods: In this cross-sectional study, staff members from a convenience sample of 50 male elite, academy and amateur football teams in Norway, Germany and Austria completed an online questionnaire focussing on the implementation of the Copenhagen Adduction Exercise. Fourteen of the staff members also completed an interview. Results: Forty-two teams (84%) reported using the Copenhagen Adduction Exercise, but the majority (65%) had modified the original programme. Modifications included changes to sets, repetitions, progressions and frequency and were particularly common among elite teams. The main reasons for modifications were managing overall player load, experiences and beliefs and individualisation. Despite modifications, all teams followed the basic principles of the original programme. Conclusion: The adoption of the Copenhagen Adduction Exercise by football teams is high, but the vast majority of teams modify the programme. Despite these modifications, the basic principles of the programme are maintained.

The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?

AIM: Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification. METHODS: This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 µg Hb/g of faeces [µg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 µg/g). CRC and SBD detection rates were compared by strategy. RESULTS: A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 µg/g, <6 µg/g for benign pathology. CONCLUSIONS: One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations S1.

The lambs of sheepfoot lane: Oldham Athletic AFC 1960-2023; football, politics and identity.

The article focuses on an overview of the history, politics and cultural identity of Oldham Athletic AFC between 1960 and 2023. During this period the club, a founding member of the Football League, played across six divisions of the game's pyramid. My hometown club, the Latics faced an existential threat to its survival following relegation to the National League in 2022, before being rescued and brought back into local ownership on the long road back to its recapturing its former status. The successes of the Frizzell and Royle eras (1969-1994) contrast with the decline of the club in the 1960s, and its gradual meltdown since the mid-1990s. These are interwoven with the economic, geopolitical and cultural dynamics of the game. The study locates the history of a small club geographically positioned within the vortex of the of the two Manchester giants and Liverpool, in English football's traditional hinterland of the industrial north west. The article has four main themes. Firstly, it examines Oldham Athletic as custodian of local identity, fusing folkloric rituals within the club's historic and contemporary nexus. Secondly, it contextualises the interface between global, glocal and grobal forces impacting on tradition, modernity and post- modernity in the club's lexicon. It then considers the themes of ownership, commodification and globalisation, debating whether Oldham Athletic stands as a bastion of anti- globalisation, or reconfirms existing global patterns at the micro level, incorporating salient theoretical perspectives in this analysis. Finally, the review evaluates whether the political and social class cleavages of the club's roots in Oldham's late Victorian industrial landscape still resonate, or if they have been marginalised by socio- economic changes since 1960.

Impact of Tracheostomy Status on Sternal Wound Infections in Children Following Median Sternotomy.

OBJECTIVE: Sternal wound infection (SWI) is a rare but potentially life-threatening complication in children following sternotomy. Risk factors include young age, extended preoperative hospitalization, and prolonged ventilatory support. Few studies have explored the impact of pre-existing tracheostomy on SWI in pediatric patients. The purpose of this study is to measure the effect of tracheostomy and other factors on SWI in children undergoing sternotomy. STUDY DESIGN: Retrospective cohort study of a 12 year period. SETTING: Tertiary children's hospital. METHODS: Children with a tracheostomy prior to sternotomy (TPS) were identified and matched by age, height, and weight to children who underwent sternotomy alone. Demographics, medical comorbidities, surgical details, SWI diagnosis and management information, and surgical outcomes were collected. RESULTS: We identified 60 unique individuals representing 80 sternotomies. The incidence of SWI was 22.5% (n = 9) in children with a tracheostomy and 2.5% (n = 1) in those without. The incidence of SWI was greater in children with a tracheostomy (90% vs 10% in those without, P = .007) and underlying pulmonary disease (90% vs 10% in those without, P = .020). Infections in the TPS group also demonstrated greater frequency of Pseudomonas aeruginosa (n = 3) and polymicrobial growth (n = 2). CONCLUSION: The risk of developing a SWI in children undergoing sternotomy is significantly greater in those with a tracheostomy and underlying pulmonary disease. Further study is needed to understand other contributing factors and ways to mitigate this risk.

Computational Design of Bidentate Hypervalent Iodine Catalysts in Halogen Bond-Mediated Organocatalysis.

In recent years, halogen bond-based organocatalysis has garnered significant attention as an alternative to hydrogen-based catalysis, capturing considerable interest within the scientific community. This transition has witnessed the evolution of catalytic scaffolds from monodentate to bidentate architectures, and from monovalent to hypervalent species. In this DFT-based study, we explored a bidentate hypervalent iodine(III)-based system that has already undergone experimental validation. Additionally, we explore various functionalisations (-CF$_3$, -CH$_3$, -tBu, -OH, -OMe, -NO$_2$, -CN) and scaffold modifications, such as sulfur oxidation, theoretically proposed for an indole-based Michael addition. The investigated systems favour bidentate O-type binding, underlining the importance of ligand coordination in catalytic activity. Electron-deficient scaffolds exhibited stronger binding and lower activation energies, indicating the pivotal role of electronic properties for $\sigma$-hole-based catalysis. Of these groups, Lewis-base-like moieties formed stabilising intramolecular interactions with hypervalent iodines when in the ortho-position. Furthermore, inductive electron withdrawal was deemed more effective than mesomeric withdrawal in enhancing catalytic efficacy for these systems. Lastly, increasing sulfur oxidation was theoretically proven to improve catalytic activity significantly.

The microbial composition of pancreatic ductal adenocarcinoma: A systematic review of 16S rRNA gene sequencing.

BACKGROUND: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. MATERIALS AND METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. RESULTS: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies. CONCLUSION: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

Gastrointestinal Permeability After Bariatric Surgery: A Systematic Review.

Gastrointestinal permeability refers to the movement of substances across the gut wall. This is mediated by endotoxemia (bacterial products entering the systemic circulation), and is associated with metabolic disease. The effect of bariatric surgery on permeability remains uncertain; the associated dietary, metabolic and weight changes are suggested to influence, or trigger, altered permeability. The primary aim of this study is to synthesize evidence and analyze the effect of bariatric surgery on permeability. A systematic review was performed, searching MEDLINE, EMBASE, and Scopus until February 2023, using MESH terms "intestinal permeability", "bariatric", for studies reporting in vivo assessment of permeability. Three cohort studies and two case series were identified (n=96). Data was heterogeneous; methodology and controls preclude meta-analysis. Gastroduodenal permeability reduced post-sleeve gastrectomy (SG). Two studies showed an increase in small intestinal permeability after biliopancreatic diversion. Two studies revealed a decrease in post-Roux-en-Y gastric bypass. One study identified increased colonic permeability six months post-SG. Evidence regarding permeability change after bariatric surgery is conflicting, notably for the small intestine. Impaired colonic permeability post-SG raises concerns regarding colonic protein fermentation and harmful dietary sequelae. There are multiple interacting variables confounding gastrointestinal permeability change; procedure type, altered microbiota and metabolic response to surgery. Further understanding of this important aspect of obesity is required, both before and after bariatric surgery.

Impact of tertiary lymphoid structures on prognosis and therapeutic response in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known to have a heterogeneous desmoplastic tumour microenvironment (TME) with a large number of immunosuppressive cells. Recently, high B-cell infiltration in PDAC has received growing interest as a potential therapeutic target. METHODS: Our literature review summarises the characteristics of tumour-associated tertiary lymphoid structures (TLSs) and highlight the key studies exploring the clinical outcomes of TLSs in PDAC patients and the direct effect on the TME. RESULTS: The location, density and maturity stages of TLSs within tumours play a key role in determining the prognosis and is a new emerging target in cancer immunotherapy. DISCUSSION: TLS development is imperative to improve the prognosis of PDAC patients. In the future, studying the genetics and immune characteristics of tumour infiltrating B cells and TLSs may lead towards enhancing adaptive immunity in PDAC and designing personalised therapies.

Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Ultrasound-guided paramedian approach: A novel technique for lumbar puncture in the Emergency Department.

Lumbar puncture is performed to evaluate for multiple neurologic conditions, including meningitis and subarachnoid hemorrhage. However, success rates with the landmark-based technique are limited. Ultrasound is most commonly used for pre-marking without dynamic guidance, which presents several limitations, including absence of real-time guidance and lack of reliability if any patient movement occurs after skin marking. We describe a novel, ultrasound-guided paramedian approach which was successfully performed in the Emergency Department setting for lumbar puncture. Physicians should consider this technique as an alternate model using real-time guidance to reduce needle passes in those with difficult anatomy.

Berkeley Open Extended Reality Recordings 2023 (BOXRR-23): 4.7 Million Motion Capture Recordings from 105,000 XR Users.

Extended reality (XR) devices such as the Meta Quest and Apple Vision Pro have seen a recent surge in attention, with motion tracking "telemetry" data lying at the core of nearly all XR and metaverse experiences. Researchers are just beginning to understand the implications of this data for security, privacy, usability, and more, but currently lack large-scale human motion datasets to study. The BOXRR-23 dataset contains 4,717,215 motion capture recordings, voluntarily submitted by 105,852 XR device users from over 50 countries. BOXRR-23 is over 200 times larger than the largest existing motion capture research dataset and uses a new, highly efficient and purpose-built XR Open Recording (XROR) file format.

The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (CHSD) continues to be the most comprehensive database of congenital and pediatric cardiothoracic surgical procedures in the world and contains information on 664,210 operations as of June 30, 2023. The 35th harvest of the STS CHSD data was undertaken in Spring 2023, spanning the 4-year period January 1, 2019, through December 31, 2022, and included 144,919 operations performed at 114 participating sites in North America. The harvest analysis was successfully executed by the STS Research and Analytic Center. The overall unadjusted mortality rate was 2.68% and has remained stable over the 4 years included in the current harvest window. Mortality is highest in neonates (7.4%) and lowest in children (1.1%). As in prior analyses, observed mortality and postoperative length of stay in the database increase with an increase in STS-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories. This quality report summarizes contemporary outcomes, provides the odds ratios for the CHSD risk model variables based on this analysis, and describes on-going efforts to improve data collection and augment analytical approaches. Lastly, 5 research publications completed in the last year using data from the CHSD are also summarized.

Artificial intelligence and point-of-care ultrasound: Benefits, limitations, and implications for the future.

The utilization of artificial intelligence (AI) in medical imaging has become a rapidly growing field as a means to address contemporary demands and challenges of healthcare. Among the emerging applications of AI is point-of-care ultrasound (POCUS), in which the combination of these two technologies has garnered recent attention in research and clinical settings. In this Controversies paper, we will discuss the benefits, limitations, and future considerations of AI in POCUS for patients, clinicians, and healthcare systems.

Lipoxin A4 yields an electrophilic 15-oxo metabolite that mediates FPR2 receptor-independent anti-inflammatory signaling.

The enzymatic oxidation of arachidonic acid is proposed to yield trihydroxytetraene species (termed lipoxins) that resolve inflammation via ligand activation of the formyl peptide receptor, FPR2. While cell and murine models activate signaling responses to synthetic lipoxins, primarily 5S,6R,15S-trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid (lipoxin A4, LXA4), there are expanding concerns about the biological formation, detection and signaling mechanisms ascribed to LXA4 and related di- and tri-hydroxy ω-6 and ω-3 fatty acids. Herein, the generation and actions of LXA4 and its primary 15-oxo metabolite were assessed in control, LPS-activated and arachidonic acid supplemented RAW 264.7 macrophages. Despite protein expression of all enzymes required for LXA4 synthesis, both LXA4 and its 15-oxo-LXA4 metabolite were undetectable. Moreover, synthetic LXA4 and the membrane permeable 15-oxo-LXA4 methyl ester that is rapidly de-esterified to 15-oxo-LXA4, displayed no ligand activity for the putative LXA4 receptor FPR2, as opposed to the FPR2 ligand WKYMVm. Alternatively, 15-oxo-LXA4, an electrophilic α,ß-unsaturated ketone, alkylates nucleophilic amino acids such as cysteine to modulate redox-sensitive transcriptional regulatory protein and enzyme function. 15-oxo-LXA4 activated nuclear factor (erythroid related factor 2)-like 2 (Nrf2)-regulated gene expression of anti-inflammatory and repair genes and inhibited nuclear factor (NF)-κB-regulated pro-inflammatory mediator expression. LXA4 did not impact these macrophage anti-inflammatory and repair responses. In summary, these data show an absence of macrophage LXA4 formation and receptor-mediated signaling actions. Rather, if LXA4 were present in sufficient concentrations, this, and other more abundant mono- and poly-hydroxylated unsaturated fatty acids can be readily oxidized to electrophilic α,ß-unsaturated ketone products that modulate the redox-sensitive cysteine proteome via G-protein coupled receptor-independent mechanisms.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Point-of-care ultrasound for airway management in the emergency and critical care setting.

Airway management is a common procedure within emergency and critical care medicine. Traditional techniques for predicting and managing a difficult airway each have important limitations. As the field has evolved, point-of-care ultrasound has been increasingly utilized for this application. Several measures can be used to sonographically predict a difficult airway, including skin to epiglottis, hyomental distance, and tongue thickness. Ultrasound can also be used to confirm endotracheal tube intubation and assess endotracheal tube depth. Ultrasound is superior to the landmark-based approach for locating the cricothyroid membrane, particularly in patients with difficult anatomy. Finally, we provide an algorithm for using ultrasound to manage the crashing patient on mechanical ventilation. After reading this article, readers will have an enhanced understanding of the role of ultrasound in airway management.

Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants.

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.