Mechanical release of homogenous proteins from supramolecular gels.

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.

Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance.

Antibiotics are considered one of the most important contributions to clinical medicine in the last century. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One form of resistance, heteroresistance, is particularly problematic; pathogens appear sensitive to a drug by common susceptibility tests. However, upon exposure to the antibiotic, resistance rapidly ascends, and treatment fails. To quantitatively explore the processes contributing to the emergence and ascent of resistance during treatment and the waning of resistance following cessation of treatment, we develop two distinct mathematical and computer-simulation models of heteroresistance. In our analysis of the properties of these models, we consider the factors that determine the response to antibiotic-mediated selection. In one model, heteroresistance is progressive, with each resistant state sequentially generating a higher resistance level. In the other model, heteroresistance is non-progressive, with a susceptible population directly generating populations with different resistance levels. The conditions where resistance will ascend in the progressive model are narrower than those of the non-progressive model. The rates of reversion from the resistant to the sensitive states are critically dependent on the transition rates and the fitness cost of resistance. Our results demonstrate that the standard test used to identify heteroresistance is insufficient. The predictions of our models are consistent with empirical results. Our results demand a reevaluation of the definition and criteria employed to identify heteroresistance. We recommend that the definition of heteroresistance should include a consideration of the rate of return to susceptibility.

Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice.

Obesity is associated with increased morbidity and mortality during bacterial pneumonia. Cyclooxygenase-2 (COX-2) and PGE2 have been shown to be upregulated in patients who are obese. In this study, we investigated the role of obesity and PGE2 in bacterial pneumonia and how inhibition of PGE2 improves antibacterial functions of macrophages. C57BL/6J male and female mice were fed either a normal diet (ND) or high-fat diet (HFD) for 16 wk. After this time, animals were infected with Pseudomonas aeruginosa in the lung. In uninfected animals, alveolar macrophages were extracted for either RNA analysis or to be cultured ex vivo for functional analysis. HFD resulted in changes in immune cell numbers in both noninfected and infected animals. HFD animals had increased bacterial burden compared with ND animals; however, male HFD animals had higher bacterial burden compared with HFD females. Alveolar macrophages from HFD males had decreased ability to phagocytize and kill bacteria and were shown to have increased cyclooxygenase-2 and PGE2. Treating male, but not female, alveolar macrophages with PGE2 leads to increases in cAMP and decreased bacterial phagocytosis. Treatment with lumiracoxib-conjugated nanocarriers targeting alveolar macrophages improves bacterial phagocytosis and clearance in both ND and HFD male animals. Our study highlights that obesity leads to worse morbidity during bacterial pneumonia in male mice because of elevated PGE2. In addition, we uncover a sex difference in both obesity and infection, because females produce high basal PGE2 but because of a failure to signal via cAMP do not display impaired phagocytosis.

Lack of prion transmission barrier in human PrP transgenic Drosophila.

While animal prion diseases are a threat to human health, their zoonotic potential is generally inefficient because of interspecies prion transmission barriers. New animal models are required to provide an understanding of these prion transmission barriers and to assess the zoonotic potential of animal prion diseases. To address this goal, we generated Drosophila transgenic for human or non-human primate PrP and determined their susceptibility to known pathogenic prion diseases, namely vCJD and classical BSE, and that with unknown pathogenic potential, namely CWD. Adult Drosophila transgenic for M129 or V129 human PrP, or non-human primate PrP developed a neurotoxic phenotype and showed an accelerated loss of survival after exposure to vCJD, classical BSE, or CWD prions at the larval stage. vCJD prion strain identity was retained after passage in both M129 and V129 human PrP Drosophila. All of the primate PrP fly lines accumulated prion seeding activity and concomitantly developed a neurotoxic phenotype, generally including accelerated loss of survival, after exposure to CWD prions derived from different cervid species, including North American white-tailed deer and muntjac, and European reindeer and moose. These novel studies show that primate PrP transgenic Drosophila lack known prion transmission barriers since, in mammalian hosts, V129 human PrP is associated with severe resistance to classical BSE prions, while both human and cynomolgus macaque PrP are associated with resistance to CWD prions. Significantly, our data suggest that interspecies differences in the amino acid sequence of PrP may not be a principal determinant of the prion transmission barrier.

Feasibility of MALDI-MSI-Based Proteomics Using Bouin-Fixed Pathology Samples: Untapping the Goldmine of Nephropathology Archives.

The application of innovative spatial proteomics techniques, such as those based upon matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology, has the potential to impact research in the field of nephropathology. Notwithstanding, the possibility to apply this technology in more routine diagnostic contexts remains limited by the alternative fixatives employed by this ultraspecialized diagnostic field, where most nephropathology laboratories worldwide use bouin-fixed paraffin-embedded (BFPE) samples. Here, the feasibility of performing MALDI-MSI on BFPE renal tissue is explored, evaluating variability within the trypsin-digested proteome as a result of different preanalytical conditions and comparing them with the more standardized formalin-fixed paraffin-embedded (FFPE) counterparts. A large proportion of the features (270, 68.9%) was detected in both BFPE and FFPE renal samples, demonstrating only limited variability in signal intensity (10.22-10.06%). Samples processed with either fixative were able to discriminate the principal parenchyma regions along with diverse renal substructures, such as glomeruli, tubules, and vessels. This was observed when performing an additional "stress test", showing comparable results in both BFPE and FFPE samples when the distribution of several amyloid fingerprint proteins was mapped. These results suggest the utility of BFPE tissue specimens in MSI-based nephropathology research, further widening their application in this field.

Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome.

BACKGROUND: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to SAB. METHODS: We conducted a retrospective observational study of adults with SAB between 20/12/2019 and 23/08/2022 (n=464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical and microbiologic features. RESULTS: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14·4% of cohort), metastatic SAB (without attributable mortality, 22·2%), neither complication (56·7%), and overlapping fatal/metastatic SAB (6·7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteraemia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. CONCLUSIONS: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality vs. improve clinical response in patients with metastatic SAB.

Universal Platform for Robust Dual-Atom Doped 2D Catalysts with Superior Hydrogen Evolution in Wide pH Media.

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

High-resolution 1H-MRSI at 9.4 T by integrating relaxation enhancement and subspace imaging.

Achieving high-resolution and high signal-to-noise ratio (SNR) in vivo metabolic imaging via fast magnetic resonance spectroscopic imaging (MRSI) has been a longstanding challenge. This study combines the methods of relaxation enhancement (RE) and subspace imaging for the first time, enabling high-resolution and high-SNR in vivo MRSI of rodent brains at 9.4 T. Specifically, an RE-based chemical shift imaging sequence, which combines a frequency-selective pulse to excite only the metabolite frequencies with minimum perturbation of the water spins and a pair of adiabatic pulses to spatially localize the slice of interest, is designed and evaluated in vivo. This strategy effectively shortens the apparent T1 of metabolites, thereby increasing the SNR during relatively short repetition time ((TR) compared with acquisitions with only spatially selective wideband excitations, and does not require water suppression. The SNR was further enhanced via a state-of-the-art subspace reconstruction method. A novel subspace learning strategy tailored for 9.4 T and RE acquisitions is developed. In vivo, high-resolution (e.g., voxel size of 0.6 × 0.6 × 1.5 mm3) MRSI of both healthy mouse brains and a glioma-bearing mouse brain in 12.5 min has been demonstrated.

Does Physiological Arousal Increase Social Transmission of Information? Two Replications of Berger (2011).

People share information for many reasons. For example, Berger (2011, N = 40) found that undergraduate participants manipulated to have higher physiological arousal were more likely to share a news article with others via email than people who had low arousal. Berger's research is widely cited as evidence of the causal role of arousal in sharing information and has been used to explain why information that induces high-arousal emotions is shared more than information that induces low-arousal emotions. We conducted two replications (N = 111, N = 160) of Berger's study, using the same arousal manipulation but updating the sharing measure to reflect the rise of information sharing through social media. Both studies failed to find an impact of incidental physiological arousal on undergraduate participants' willingness to share news articles on social media. Our studies cast doubt on the idea that incidental physiological arousal-in the absence of other factors-impacts people's decisions to share information on social networking sites.

Reversibly Tuning the Viscosity of Peptide-Based Solutions Using Visible Light.

Light can be used to design stimuli-responsive systems. We induce transient changes in the assembly of a low molecular weight gelator solution using a merocyanine photoacid. Through our approach, reversible viscosity changes can be achieved via irradiation, delivering systems where flow can be controlled non-invasively on demand.

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

BACKGROUND: Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. METHODS: Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. RESULTS: The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. CONCLUSIONS: Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

Short-term psychosocial outcomes of adding a non-contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening.

OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.

Analysis of the adhesive secreting cells of Arion subfuscus: insights into the role of microgels in a tough, fast-setting hydrogel glue.

The slug Arion subfuscus produces a tough, highly adhesive defensive secretion. This secretion is a flexible hydrogel that is toughened by a double network mechanism. While synthetic double network gels typically require extensive time to prepare, this slug creates a tough gel in seconds. To gain insight into how the glue forms a double-network hydrogel so rapidly, the secretory apparatus of this slug was analyzed. The goal was to determine how the major components of the glue were distributed and mixed. Most of the glue comes from two types of large unicellular glands; one secretes polyanionic polysaccharides in small, membrane-bound packets, the other secretes proteins that appear to form a cross-linked network. The latter gland shows distinct regions where cross-linking appears to be occurring. These regions are darker, more homogeneous and appear more solid than the rest of the secretory material. The enzyme catalase is highly abundant in these regions, as are basic proteins. These results suggest that a rapid oxidation event occurs in this protein-containing gland, triggering cross-linking before the glue is released. The cross-linked microgels would then join together after secretion to form a granular hydrogel. The polysaccharide-filled packets would be mixed and interspersed among these microgels and may contribute to joining them together. This is an unexpected and highly effective way to form a tough gel rapidly.

Prospective Evaluation of Artificial Intelligence Triage of Incidental Pulmonary Emboli on Contrast-Enhanced CT Examinations of the Chest or Abdomen.

Background: Artificial intelligence (AI) algorithms improved detection of incidental pulmonary embolism (IPE) on contrast-enhanced CT (CECT) examinations in retrospective studies; however, prospective validation studies are lacking. Objective: To assess the effect on radiologists' real-world diagnostic performance and report turnaround times of a radiology department's clinical implementation of an AI triage system for detecting IPE on CECT examinations of the chest or abdomen. Methods: This prospective single-center study included consecutive adult patients who underwent CECT of the chest or abdomen for reasons other than PE detection from May 12, 2021 to June 30, 2021 (phase 1) or from July 1, 2021 to September 29, 2021 (phase 2). Before phase 1, the radiology department installed a commercially available AI triage algorithm for IPE detection that automatically processed CT examinations and notified radiologists of positive results through an interactive floating widget. In phase 1, the widget was inactive, and radiologists interpreted examinations without AI assistance. In phase 2, the widget was activated, and radiologists interpreted examinations with AI assistance. A review process involving a panel of radiologists was implemented to establish the reference standard for the presence of IPE. Diagnostic performance and report turnaround times were compared using Pearson Chi-square test and Wilcoxon rank-sum test, respectively. Results: Phase 1 included 1467 examinations in 1434 patients (mean age, 53.8±18.5 years; 753 male, 681 female); phase 2 included 3182 examinations in 2886 patients (mean age, 55.4±18.2 years; 1520 male, 1366 female). The frequency of IPE was 1.4% (20/1467) in phase 1 and 1.6% (52/3182) in phase 2. Radiologists without AI, in comparison with radiologists with AI, showed significantly lower sensitivity (80.0% vs 96.2%, P=.03), without a significant difference in specificity (99.1% vs 99.9%, P=.58), for detection of IPE. The mean report turnaround time for IPE-positive examinations was not significantly different between radiologists without AI and radiologists with AI (78.3 vs 64.6 min, P=.26). Conclusion: An AI triage system improved radiologists' sensitivity for IPE detection on CECT examinations of the chest or abdomen without significant change in report turnaround times. Clinical Impact: This prospective real-world study supports the use of AI assistance for maximizing IPE detection.

Study protocol for the ACTIVE SCHOOL study investigating two different strategies of physical activity to improve academic performance in Schoolchildren.

BACKGROUND: Previous research has suggested that school-based physical activity (PA) interventions may have a positive impact on academic performance. However, existing literature on school-based interventions encompasses various forms of PA, spanning from vigorous intensity PA outside the academic classes to light intensity PA and movement integrated into academic learning tasks, and results on academic performance are inconclusive. ACTIVE SCHOOL will implement two different PA interventions for one school year and assess the effects on the pupils' academic performance, with math performance as the primary outcome. METHODS/DESIGN: The ACTIVE SCHOOL project consists of two phases: 1) Development phase and 2) Randomized Controlled Trial (RCT). In phase one, two interventions were developed in collaboration with school staff. The two interventions were tested in an 8-weeks feasibility study. In phase two, a RCT-study with three arms will be conducted in 9-10-year-old children for one school year. The RCT-study will be carried out in two intervention rounds during the school years 2023/2024 and 2024/2025. Schools will be randomized to one of two interventions or control;1) Run, Jump & Fun intervention (4 × 30 min/week of moderate-to-vigorous physical activity; 2) Move & Learn intervention (4 × 30 min/week focusing on embodied learning in math and Danish lessons); or 3) a control condition, consisting of normal teaching practices. Outcome measures include academic performance, PA level, cognitive functions, cardiorespiratory fitness, anthropometry, well-being and school motivation (collected before, during and after the intervention period). A process evaluation will be conducted to assess implementation. DISCUSSION: The ACTIVE SCHOOL study will expand knowledge regarding the impact of PA on academic performance. The study will have the potential to significantly contribute to future research, as well as the scientific and educational debate on the best way to implement PA to support education and learning. TRIAL REGISTRATION: The study was registered on the 25th of October 2022 in ClinicalTrials.gov, NCT05602948.

Association Between Right Ventricular Systolic Parameters Measured by Echocardiography and Stroke Volume Derived From Pulmonary Artery Catheter in Ischemic Cardiogenic Shock.

OBJECTIVE: To determine the right ventricular (RV) systolic function echocardiographic parameter best associated with native stroke volume (SV) by thermodilution via a pulmonary artery catheter (PAC) in patients admitted to intensive care with ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study of 43 prospectively identified patients admitted to a tertiary cardiac intensive care unit in London, United Kingdom. INTERVENTIONS: Simultaneous collection of comprehensive transthoracic echocardiographic, clinical, and PAC-derived hemodynamic data. Seven RV systolic function parameters were correlated with the PAC-derived SV. MEASUREMENTS AND MAIN RESULTS: The median patient age was 61 years (interquartile range [IQR], 52-67 years), and 36 of the 43 patients (84%) were male. The median PAC-derived SV and left ventricular ejection fraction were 57 mL (IQR, 39-70 mL) and 31% (IQR, 22%-35%), respectively. The RV outflow tract velocity time integral (RVOT VTI) and tricuspid plane systolic excursion (TAPSE) correlated significantly with the PAC-derived SV (r = 0.42 [p = 0.007] and r = 0.37 [p = 0.02], respectively). The RVOT VTI was independently associated with and predicted low PAC-derived SV (odds ratio, 1.3; p = 0.03) with a good area under the curve (AUC = 0.71; p = 0.02). An RVOT VTI <12.7 cm predicted low PAC-derived SV with a sensitivity of 66% and specificity of 72%. CONCLUSIONS: RVOT VTI is the echocardiographic RV systolic function parameter that best correlates with PAC-derived native SV in patients with STEMI complicated by CS. This parameter can help guide the hemodynamic management of this cohort.

Predictive modeling of ambulatory outcomes after spinal cord injury using machine learning.

STUDY DESIGN: Retrospective multi-site cohort study. OBJECTIVES: To develop an accurate machine learning predictive model using predictor variables from the acute rehabilitation period to determine ambulatory status in spinal cord injury (SCI) one year post injury. SETTING: Model SCI System (SCIMS) database between January 2000 and May 2019. METHODS: Retrospective cohort study using data that were previously collected as part of the SCI Model System (SCIMS) database. A total of 4523 patients were analyzed comparing traditional models (van Middendorp and Hicks) compared to machine learning algorithms including Elastic Net Penalized Logistic Regression (ENPLR), Gradient Boosted Machine (GBM), and Artificial Neural Networks (ANN). RESULTS: Compared with GBM and ANN, ENPLR was determined to be the preferred model based on predictive accuracy metrics, calibration, and variable selection. The primary metric to judge discrimination was the area under the receiver operating characteristic curve (AUC). When compared to the van Middendorp all patients (0.916), ASIA A and D (0.951) and ASIA B and C (0.775) and Hicks all patients (0.89), ASIA A and D (0.934) and ASIA B and C (0.775), ENPLR demonstrated improved AUC for all patients (0.931), ASIA A and D (0.965) ASIA B and C (0.803). CONCLUSIONS: Utilizing artificial intelligence and machine learning methods are feasible for accurately classifying outcomes in SCI and may provide improved sensitivity in identifying which individuals are less likely to ambulate and may benefit from augmentative strategies, such as neuromodulation. Future directions should include the use of additional variables to further refine these models.

Explant of an infected, endo-trashed IVC filter in an immunosuppressed patient with chronically occluded iliocaval stents.

BACKGROUND: In the absence of a contiguous bowel perforation or intraabdominal source, infection of a retained vena cava filter in an occluded IVC has never been described. OBJECTIVE: To describe a case of an infected IVC filter in a chronically occluded iliocaval segment. METHODS: Here we present a case of an immunosuppressed 35-year-old female with chronically occluded iliocaval stents and an extensive staphylococcus hominis infection of a previously endo-trashed Bard Eclipse® filter. Particular attention is paid to supportive imaging in establishing the diagnosis and technical aspects of successful device explant and retroperitoneal debridement. RESULTS: At 6 months postoperatively, the patient was doing well without evidence of recurrent infection. Her lower extremity edema was controlled with compression alone. CONCLUSIONS: The main objective of this operation was source control with debridement of the infection and removal of the filter and as much of the iliac vein as safely possible. Superinfection of a previously placed iliocaval stents and inferior vena cava filter remains a concern in patients with retroperitoneal infection and chronic iliocaval occlusion. Operative explant and debridement can be safely performed in patients with favorable cardiopulmonary risk.

Resuscitation on the field of play: a best-practice guideline from Resuscitation Council UK.

Sudden cardiac arrest (SCA) is the leading cause of sudden death in athletes during high-level, organised sport. Patient-related and event-related factors provide an opportunity for rapid intervention and the potential for high survival rates. The aim of this consensus was to develop a best-practice guideline for dedicated field-of-play medical teams responding to SCA during an organised sporting event. A task-and-finish group from Resuscitation Council UK identified a stakeholder group of relevant experts and cardiac arrest survivors in March and April 2022. Together, they developed a best-practice guideline using the best available evidence. A public consultation period further refined the guideline before it was finalised in December 2023. Any sudden collapse, without rapid recovery during sporting activity, should be considered an SCA until proven otherwise. Field-of-play medical teams should be empowered to access the collapsed athlete as soon as possible and perform initial essential interventions in situ. This includes a suggested minimum of three cycles of cardiopulmonary resuscitation and defibrillation in persistent shockable rhythms while other aspects of advanced life support are initiated. There should be careful organisation and practice of the medical response, including plans to transport athletes to dedicated facilities for definitive medical care. This best-practice guideline complements, rather than supersedes, existing resuscitation guidelines. It provides a clear approach to how to best treat an athlete with SCA and how to organise the medical response so treatments are delivered effectively and optimise outcomes.