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by Nikola Lübbering, Alexander Krogmann, Felix Jansen, Eicke Latz, Georg Nickenig, Sebastian Zimmer
BackgroundAtherosclerosis is a chronic inflammatory disease driven by endothelial dysfunction, cholesterol accumulation, and immune activation leading to thrombosis and vascular stenosis. While LDL-lowering therapies are firmly established, targeting the underlying inflammation is still an emerging strategy. Cholesterol crystals (CC) contribute to inflammation by activating the NLRP3 inflammasome in monocytes and promoting disease progression. Cyclodextrin (CD), an FDA-approved drug carrier, has shown atheroprotective effects by enhancing cholesterol metabolism and reducing inflammation in preclinical models. This study investigated whether CC-uptake in human monocytes, a prerequisite for inflammasome activation, is also influenced by CD pretreatment.
MethodsHuman peripheral mononuclear cells were isolated from whole blood samples provided by 76 patients undergoing coronary angiography at the University Hospital Bonn between November 2017 and February 2018. After separation, peripheral mononuclear cells were stimulated with 2-Hydroxypropyl-γ-Cyclodextrin and CC. CC-uptake by monocytes was analyzed using flow cytometry.
ResultsCC-uptake by monocytes varied greatly between patients (8–37%), with lower uptake observed in patients with elevated leukocytes (p = 0.0058) and diabetes mellitus (p = 0.0448). CD-pretreatment significantly reduced CC-uptake (20.1% ± 0.8% vs. 15.0% ± 0.6%, p p = 0.0316), requirement for percutaneous coronary intervention (PCI) (p = 0.0030), and elevated leucocyte levels (p = 0.0135) had lower CCΔCD, suggesting a link between systemic inflammation and attenuated CD efficacy.
ConclusionWe demonstrated that CD significantly reduced CC-uptake in patients undergoing coronary angiography, which supports its role in inhibiting CC-phagocytosis and promoting cholesterol efflux. Interestingly, patient response to CD varied, with those exhibiting greater systemic inflammation or CAD showing a less pronounced reduction in CC-uptake. Our findings provide insight into the atheroprotective mechanisms of CD and suggest its potential utility in evaluating individual cardiovascular risk and monitoring CD-based therapeutic interventions in humans.
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, inflammatory bowel diseases (IBDs) of unknown origin, affecting the gastrointestinal tract and often causing extraintestinal symptoms. Conventional treatments (eg, glucocorticosteroids, immunomodulators) and targeted advanced treatments, including anti-TNFα, antibodies to p40 subunit of IL-12/23, antibodies to p19 subunit of IL-23, anti-α4β7 integrin, Janus kinase inhibitors (JAKis) and sphingosine-1-phosphate receptor (S1PR) modulators, do not achieve sustained responses for all patients, leaving significant unmet therapeutic needs.
This prospective, multi-centre observational study will follow a cohort of 240 patients across multiple study centres within NHS trusts in the UK who are initiating or switching biologics, specifically anti-TNFα and anti-α4β7 integrin for UC, and anti-TNFα, antibodies to p40 subunit of IL-12/2 and JAKi for CD. Through comprehensive profiling of immunological, transcriptional, microbiome, genetic and proteomic markers at baseline, week 12, and week 52, this study aims to uncover non-invasive biomarkers that predict response to these drug classes, ultimately advancing personalised medicine in IBD.
Ethical approval for the Nottingham/AstraZeneca study was granted by the West of Scotland Research Ethics Committee. Recruitment began in December 2022 and is currently ongoing at 10 NHS Trust sites across the UK. Study findings will be disseminated by publication in peer-reviewed journals and presentations at relevant national and international conferences.
by Jorman H. Tejada-Perdomo, Valentina Gutierrez-Perdomo, Juana V. Agudelo-Castro, Jorge A. Pérez-Gamboa, Alejandro Weinstein, Sebastián San Martín, Rodrigo Salas, Jorge A. Ramos-Castaneda
The use of devices that facilitate rapid airway isolation is essential when managing critical patients in emergencies. In recent years, additive manufacturing has emerged as an innovative, versatile, and accessible technology for developing medical devices. This study presents the design, development, and validation of an extraglottic medical device created using computer-aided design tools and stereolithographic 3D printing to facilitate blind intubation by first responders. The device was iteratively modeled and fabricated with biocompatible materials; validation in airway simulators and human cadaveric specimens assessed dimensions, friction, intubation technique, and learning curve, and ease of use was rated with a Likert scale. Ten iterations led to a final design with low friction and minimal cervical manipulation; ramp angle, cup geometry, and distal tip were optimized for tube passage, and BioMed Flex 80A showed high strength and anatomical compatibility. The final version is a safe, reusable, and functional alternative for airway management and blind orotracheal intubation, particularly in emergencies and resource-limited settings; clinical validation in live patients is still needed.by Sebastian Medina, Eduardo Romero, Angel Cruz-Roa, Fabio A. González
Classification methods based on deep learning require selecting between fully-supervised or weakly-supervised approaches, each presenting limitations in uncertainty quantification and interpretability. A framework unifying both supervision modes while maintaining quantifiable interpretation metrics remains unexplored. We introduce WiSDoM (Weakly-Supervised Density Matrices), which uses kernel matrices to model probability distributions of input data and their labels. The framework integrates: (1) differentiable kernel density matrices enabling stochastic gradient descent optimization, (2) local-global attention mechanisms for multi-scale feature weighting, (3) data-driven prototype generation through kernel space sampling, and (4) ordinal regression through density matrix operations. WiSDoM was validated through supervised patch classification (κ = 0.896) and weakly-supervised whole-slide classification (κ = 0.930) on histopathology images. WiSDoM generates three quantifiable outputs: posterior probability distributions, variance-based uncertainty maps, and phenotype prototypes. Through validation in a Gleason grading task at a patch and whole-slide level using histopathology images, WiSDoM demonstrated consistent performance across supervision modes (κ > 0.89) and prototype interpretability (0.88 expert agreement). These results show that kernel density matrices can serve as a foundation for classification models requiring both prediction interpretability and uncertainty quantification across supervision modes.Chronic limb ischemia (CLI) is a significant health issue, particularly among patients with diabetes who are at elevated risk of diabetic foot ulcers (DFU) due to peripheral neuropathy and ischemia. In Singapore, approximately one in six adults is affected by diabetes, with a lifetime risk of developing DFU ranging from 15% to 25%. This paper examines the indications, surgical techniques and postoperative protocols for transverse tibial transport (TTT), an innovative limb salvage procedure implemented in a general hospital in Singapore and presents our early experience with this technique. All six patients in our study successfully achieved limb salvage with complete wound healing, with a median healing time of 4 months. Four patients required additional wound debridement and skin coverage to facilitate healing. Importantly, none of the patients experienced pin site infections during the procedure or throughout the postoperative healing phase. Our study demonstrates favourable outcomes and underscores the clinical utility of TTT in augmenting the multimodal treatment of recalcitrant DFUs.
Although healthcare infrastructure has improved in recent years, the preoperative journey of patients is often accompanied by anxiety. Allowing patients to walk to the operating theatre is a simple, yet underexplored strategy that may enhance their sense of autonomy and reduce anxiety. As patient-centred care gains importance, evaluating the effects of this approach on patient-reported outcomes may be more relevant than widely assumed.
In this scoping review, we aim to analyse the published literature on preoperative walking into the operating theatre and patient-reported outcomes, such as anxiety and satisfaction.
This study was a scoping review that followed the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Scoping Review extension guidelines.
Inclusion criteria were adult patients undergoing elective surgery and walking to the operating theatre. Data were extracted using a standardised form, and critical appraisal was performed by using ROBINS-I V2.0, RoB2 and ROB-E tools.
Embase, MEDLINE, Cochrane databases (OVID) and CINAHL (EBSCOhost) were searched up to 31st January 2025.
Our search identified 958 articles, with seven trials included in the final analysis. The studies, published between 1994 and 2022, involved 3001 patients from North America, Asia and Europe. The interventions varied, but most patients reported improved satisfaction and reduced anxiety when walking to the operating theatre. No adverse events were reported, although patient preferences varied, with younger patients more likely to prefer walking.
Walking to the theatre positively impacts patient satisfaction and autonomy. However, patient selection is key, as not all individuals are physically or mentally prepared for walking. Future research could explore unaccompanied walking and its effects on hospital resource utilisation. Preoperative walking is a beneficial intervention that enhances patient satisfaction and reduces anxiety, providing a feasible alternative to bed transport for many elective surgical patients.
No patient or public involvement.
by Yordi Sebastián Tamayo-Molina, Juan Felipe Valdés-López, Geysson J. Fernandez, Silvio Urcuqui-Inchima
Dengue virus (DENV), the etiological agent of dengue fever, remains a global health concern, leading to severe illness and death in the absence of any definitive cure. Research has shown that vitamin D may reduce DENV replication in vitro and that dengue patients with low or deficient vitamin D levels are at higher risk of severe dengue. Studies indicate that viral replication is inhibited in human monocyte-derived macrophages (MDM) differentiated in the presence of vitamin D (D3MDM), suggesting that vitamin D may prevent DENV entry into host cells. However, despite these findings, the role of vitamin D in regulating the temporal expression patterns of genes as early, mid, and late transcriptional profile of DENV-infected macrophages remains unclear. Therefore, utilizing a kinetic transcriptomic profile is crucial. This approach provides detailed insights into the dynamic changes in gene expression over time, helping to clarify how vitamin D can modulate the immune response at critical stages of DENV infection. To address the transcriptional dynamics, we conducted a comprehensive analysis of gene expression patterns in MDM and D3MDM infected with Dengue virus serotype 2 (DENV-2). Utilizing bulk RNA sequencing alongside a standard viral growth curve, we systematically analyzed transcriptional kinetics by selecting key time points: 1.5, 3, 5.5, and 10 hours post-infection (h.p.i.) to monitor early viral entry and replication events and 24 h.p.i. to assess gene expression during peak viral particle production. Our temporal analysis revealed a progressive increase in cellular transcripts within the first hour of infection, with a more pronounced gene expression pattern in DENV-2-infected MDM compared to DENV-2-infected D3MDM at this early stage. Enrichment analysis indicated a reduced inflammatory response in DENV-2-infected D3MDM. Additionally, transcription factor analysis suggested diminished NF-κB signaling, but enhanced IRF5 activity was elevated in the DENV-2-infected D3MDM. High-dimensional clustering analysis identified nine unique gene clusters across both macrophage types, with notable upregulation of genes associated with antiviral activity, including IDO1, ISG20, OASL, IFI44L, RSAD2, IFIT1, MX1, EPSTI1, CXCL10, and CXCL11 in DENV-2-infected D3MDM at 1.5 h.p.i., suggesting an enhanced early antiviral response. These findings indicate that vitamin D modulates the magnitude and diversity of the early transcriptional responses, highlighting its potential as a therapeutic option to mitigate DENV severity.Latin American countries have long struggled with socioeconomic inequalities and health equity. In 2007, Ecuador implemented a health reform to address these issues by making public health services free, coordinating finances between subsystems and increasing the state’s health budget. This study evaluates whether Ecuador’s health system reform (2007–2017) reduced out-of-pocket (OOP) health spending, catastrophic health spending (CHS) and socioeconomic inequalities in CHS.
Cross-sectional study.
Secondary data available of households from the 2006 and 2014 National Living Standards Measurement surveys.
Descriptive statistics (means and medians) and log-binomial regression were applied to assess prevalence of OOP and socioeconomic inequalities (residence, region, health insurance status and wealth) in catastrophic health expenditure (CHE) for each period and over time.
Overall, there was a significant reduction of 14% points in the proportion of households with OOP healthcare expenditure. The prevalence of CHE decreased from 17% to 10% and within each socioeconomic group over time. Significant reductions in relative risk were observed in all socioeconomic variables. The inequality in CHE decreased significantly in households placed in rural areas (relative difference (RD): 0.88; 95% CI: 0.79 to 0.97) and poorest (RD: 0.82; 95% CI: 0.69 to 0.97); however, it increased within regions (RD: 0.58; 95% CI: 0.44 to 0.76) and for uninsured households (RD: 1.39; 95% CI: 0.95 to 2.04).
This study suggests that recent health reform effectively reduced OOP healthcare expenditure, CHE and some socioeconomic inequalities. Future reforms should further invest in key areas, expand health insurance for the most disadvantaged and monitor progress towards universal health coverage to address persistent inequalities.
Introducción: La enfermería, como disciplina, demanda un alto nivel de compromiso y responsabilidad, debe abordar conocimientos esenciales para la labor diaria como las responsabilidades tanto éticas, civiles y penales. Objetivo. Este estudio tiene como finalidad evaluar el nivel de conocimientos sobre las responsabilidades civiles, éticas y legales que poseen los profesionales de Enfermería de un hospital público del interior del país, el Hospital Distrital Inmaculada Concepción de la Ciudad de Caaguazú de Paraguay, en el año 2023. Metodología. Se llevó a cabo un estudio cuantitativo, descriptivo de corte transversal con componente analítico. La población estuvo compuesta por 130 profesionales de Enfermería que realizan funciones en las áreas asistenciales y de salud pública. La técnica utilizada fue la encuesta por medio de un instrumento con 25 preguntas, el cuestionario fue validado mediante prueba piloto y la revisión por parte de un panel de expertos. Resultados. De los 130 profesionales de Enfermería encuestados el 77,69% eran del sexo femenino, con promedio de edad entre 30 a 36 años y el 63,85% eran casados, el 49,23% (64) tienen nivel de conocimiento deficiente sobre las responsabilidades penales y el 77.69% (101) poseen el nivel de conocimiento excelente en cuanto a responsabilidad civil, el 44.62% (58) de los profesionales tiene nivel de conocimiento regular sobre responsabilidad ética. Discusión. Más de la mitad de los profesionales de enfermería menores de 32 años tienen nivel de conocimiento malo sobre las responsabilidades penales, lo que resalta la necesidad de implementar programas de formación continua en estas áreas críticas, además de ser un respaldo legal en el actual diario de su profesión.
ABSTRACT
Introduction. Nursing, as a discipline, demands a high level of commitment and responsibility, it must address essential knowledge for daily work such as ethical, civil and criminal responsibilities. Objective. This study aims to evaluate the level of knowledge about civil, ethical and legal responsibilities that nursing professionals have in a public hospital in the interior of the country, the Inmaculada Concepción District Hospital of the City of Caaguazú in Paraguay, in the year 2023. Methodology. A quantitative, descriptive cross-sectional study with an analytical component was carried out. The population was made up of 130 nursing professionals who perform functions in the healthcare and public health areas. The technique used was the survey using an instrument with 25 questions, the questionnaire was validated through pilot testing and review by a panel of experts. Results. Of the 130 nursing professionals surveyed, 77.69% were female, with an average age between 30 to 36 years and 63.85% were married, 49.23% (64) have a poor level of knowledge about the criminal responsibilities and 77.69% (101) have an excellent level of knowledge regarding civil liability, 44.62% (58) of professionals have an excellent level of knowledge. of regular knowledge about ethical responsibility. Discussion. More than half of nursing professionals under 32 years of age have a poor level of knowledge about criminal responsibilities, which highlights the need to implement continuous training programs in these critical areas, in addition to being legal support in the current journal of his profession.
To identify key aspects of recovery-oriented practice in caring for people with mental ill-health in general emergency departments.
A modified Delphi study with three rounds.
A 24-member expert panel was recruited consisting of people with lived experience of mental ill-health, registered nurses working in emergency care, registered nurses specialised in psychiatric and mental health nursing and mental health recovery researchers. In the initial round, important aspects of recovery-oriented practice were identified through focus group interviews. Thematic analysis generated statements that were then reformulated as a questionnaire for subsequent rounds. The experts rated each statement's perceived importance on a 5-point Likert scale. The consensus level was set at ≥ 80%. Descriptive statistics were used to analyse the data.
Consensus was reached on the importance of 39 of 73 statements, with ≥ 80% deemed ‘very important’ in recovery-oriented practice in general emergency departments.
The study emphasises the delicate balance between the essential elements of recovery-oriented practice, their practical feasibility and the predominant biomedical perspective in general emergency department care. It proposes strategies to empower nursing staff and managers to adopt recovery-oriented practices that enhance the quality of care for people with mental ill-health. Enabling staff by providing the necessary prerequisites and a care environment that supports reflective practices is crucial. The responsibility for facilitating these changes needs to be a shared commitment between nursing staff and managers.
The identified issues can serve as a framework for interventions, education and training to support the integration of recovery-oriented practice in general emergency care. They can also be used to develop tools for evaluating emergency care environments and promoting alignment with recovery-oriented principles.
Problem addressed: People with mental ill-health are at risk of being neglected, judged and dismissed in general emergency department care, creating obstacles to their mental health recovery. Main results: The Delphi study identified 39 key aspects of recovery-oriented practice in general emergency departments, emphasising person-centred, strength-based, collaborative and reflective care. Impact: The research seeks to establish a foundation for developing training programmes, education and interventions and for the integration of recovery-oriented practices in general emergency care. It thus has the potential to enhance the quality and equality of care for patients with mental ill-health in emergency care. The impact extends to nursing staff and managers as it seeks to empower them to systematically reflect on and reevaluate established emergency department practices to ensure that every person, irrespective of their health condition, is treated with dignity and respect in emergency department settings.
The CREDES guidance on conducting and reporting Delphi studies.
The authors have nothing to report.
Healthcare consumers require diverse resources to assist their navigation of complex healthcare interactions, however, these resources need to be fit for purpose.
In this study, we evaluated the utility, usability and feasibility of children, families and adults requiring long-term intravenous therapy using a recently developed mobile health application (App), intravenous (IV) Passport.
Multi-site, parallel, multi-method, prospective cohort study.
A multi-site, multi-method study was carried out in 2020–2021, with 46 participants (20 adults, 26 children/family) reporting on their experiences surrounding the use of the IV Passport for up to 6 months.
Overall, utility rates were acceptable, with 78.3% (N = 36) using the IV Passport over the follow-up period, with high rates of planned future use for those still active in the project (N = 21; 73%), especially in the child/family cohort (N = 13; 100%). Acceptability rates were high (9/10; IQR 6.5–10), with the IV Passport primarily used for documenting new devices and complications. Thematic analysis revealed three main themes (and multiple subthemes) in the qualitative data: Advocacy for healthcare needs, Complexity of healthcare and App design and functionality.
Several recommendations were made to improve the end-user experience including ‘how to’ instructions; and scheduling functionality for routine care.
The IV Passport can be safely and appropriately integrated into healthcare, to support consumers.
Patient-/parent-reported feedback suggests the Intravenous Passport is a useful tool for record-keeping, and positive communication between patients/parents, and clinicians.
Not applicable.
Consumers reported their experiences surrounding the use of the IV Passport for up to 6 months.
Objetivo principal: Mejorar la calidad del sueño y descanso de los pacientes en el servicio de urgencias mediante la participación y cono-cimiento de las percepciones de los profesionales sanitarios. Metodología: Un total de 173 profesionales sanitarios (79 enfermeras/os, 33 TCAE, 29 médicos/as y 32 celadores/as) cumplimentaron el cuestionario ad hoc de percepción de los profesionales sobre cómo afecta la luz y ruido al sueño y descanso de los pacientes. Resultados principales: Aspectos relacionados con la organización y dinámicas de trabajo, las competencias, habilidades y cuidados llevados a cabo por los profesionales daban lugar a distinciones en la participación de responder al cuestionario y en las percepciones de los profesionales sobre cómo la luz y ruido afecta al sueño y descanso de los pacien-tes, lo cual remarcaba la necesidad de evaluar factores perturbadores ambientales y establecer estrategias, medidas, intervenciones y cuidados para mejorar la calidad de sueño de los pacientes. Por tanto, los resultados de este trabajo aportaban nuevos datos en compa-ración con los datos de escasos estudios sobre la necesidad de conocer la percepción de los profesionales sanitarios sobre factores perturbadores ambientales que afectan al sueño/descanso de los pacientes, particularmente en el servicio de urgencias. Conclusión principal: Existe una variabilidad de las diferentes categorías de profesionales sanitarios en relación a la participación en contestar al cuestionario ad hoc, así como diferencias significativas entre las percepciones sobre cómo afecta la luz y ruido sobre el sueño/descanso de los pacientes. Por tanto, se plantean perspectivas de futuro y se alude a estrategias dirigidas a los pacientes, profesionales y organi-zación/entorno de trabajo para mejorar la calidad de sueño de los pacientes en el servicio de urgencias.
Introducción: los pacientes que se encuentran hospitalizados sufren un conjunto de reacciones y sentimientos que conlleva generalmente proble-mas de sueño en el hospital, donde el trabajo es continuo en relación a los cuidados que requieren los pacientes y donde es necesario considerar la tecnología que caracteriza a las diferentes unidades, por el ruido que se produce y la luz que requieren los profesionales para llevar a cabo el trabajo. El ruido y la luz son los factores ambientales que afectan en mayor medida a los pacientes hospitalizados. El objetivo es comprobar, identifi-car y discutir cuales son los factores perturbadores ambientales que afectan al sueño/descanso de los pacientes ingresados en el hospital. Material y métodos: se llevó a cabo una búsqueda bibliográfica en las principales bases de datos primarias y secundarias como Pubmed®, CINAHL®, Coch-rane® y Google Acádemico® de los últimos 10 años. Resultados: se obtuvo un gran número de artículos, de los cuales se seleccionaron los que fueron más relevantes según el objetivo de esta revisión narrativa crítica. Discusión y conclusiones: existe una gran complejidad y variabilidad en las metodologías de los diferentes estudios relacionados con factores perturbadores ambientales, pero también en los últimos años se está prestando mayor atención a la investigación sobre los factores que afectan a sueño y descanso de los pacientes ingresados en el hospital. Se puede concluir que el ruido y la luz son los factores perturbadores ambientales principales que afectan al sueño/descanso de los pacientes hospitalizados y que se necesita más investigación de alta calidad para superar las limitaciones y dificultades de estudios previos y fortalecer los cuidados de enfermería basados en la evidencia.
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