Conectar
by Ryosuke Segawa, Makiko Yagisawa, Chihiro Miyata, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune responses through dendritic cell activation, and its aberrant regulation is implicated in TSLP-associated inflammatory disorders including atopic dermatitis. We previously demonstrated that hypoxia-inducible factor (HIF) suppresses TSLP expression in human keratinocyte cells; however, the underlying mechanism remained unclear. In this study, we aimed to explore the suppressive mechanism of enarodustat, an HIF-prolyl hydroxylase inhibitor. Enarodustat selectively suppressed TSLP expression induced by the fibroblast-stimulating lipopeptide (FSL-1), a toll like receptor 2/6 agonist in HaCaT, a human keratinocyte cell line. Although both the nuclear factor-κB (NF-κB) and activator protein (AP)-1 contributed to FSL-1-induced TSLP induction, enarodustat preferentially attenuated AP-1 signaling by reducing c-Jun N-terminal kinase (JNK) phosphorylation. This JNK dephosphorylation required both HIF1α and HIF2α and was accompanied by increased expression of dual-specificity phosphatases (DUSPs), which target JNK for dephosphorylation. Collectively, our findings identify a previously uncharacterized HIF–DUSP–JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis.The substantial case detection gap in the field of child tuberculosis (TB) disease is largely driven by inadequate diagnostic tools and approaches. Chest radiographs (CXRs) remain a key component in the evaluation of children and young adolescents (0–15 years) with presumptive TB, aiding clinicians in making the diagnosis and discriminating children with TB from those with other diseases. Widespread use and optimal interpretation of CXR is hampered by a lack of access to well-trained specialists to interpret images. Artificial intelligence CXR interpretation software, termed computer-aided detection (CAD), is now well developed for adults, yet few products have been evaluated in children. The CXR features of child TB are different from those of adults, and as a result, the performance of these CAD algorithms, largely developed for use in adults, will be suboptimal when used in children. Adapting, or fine-tuning adult CAD algorithms, using CXR images from children with presumptive TB, could allow optimisation of these products for use in children. We, therefore, set out to develop a large image and data repository collected from children evaluated for TB (called Catalysing Artificial Intelligence for Paediatric Tuberculosis Research, CAPTURE) with the purpose of evaluating current CAD products and then working with developers and other partners to optimise CAD algorithms for use in children.
We identified approximately 20 studies, from which potentially up to 11 000 CXRs could be used for the proposed project. CXRs and data were eligible for inclusion in the CAPTURE repository if collected from high-quality child TB diagnostic studies that enrolled children with presumptive TB and if CXRs were obtained as part of the baseline assessment. All lead investigators of these studies are members of the CAPTURE consortium. The images and metadata contributed are centrally collated and the key variable of TB case classification as confirmed, unconfirmed or unlikely TB, using an established consensus case definition, is available. All CXRs included in the CAPTURE repository have a consensus radiological interpretation allocated by a panel of independent expert child TB CXR readers who have classified them as ‘unreadable’, ‘normal’, ‘abnormal typical of TB’ or ‘abnormal not typical of TB’. To determine diagnostic performance of existing CAD products, we will evaluate these against a primary composite clinical reference standard (confirmed TB and unconfirmed TB vs unlikely TB), as well as other secondary microbiological and radiological reference standards. A subset of images will be subsequently allocated to a ‘training set’ and made available to developers, academic groups or other parties to either develop novel paediatric CAD products or fine-tune existing adult ones, which will then be re-evaluated by the CAPTURE team using an image subset (‘validation set’) that is independent of the training set.
The CAPTURE study has been approved by Stellenbosch University Health Research Ethics Committee (N22/09/113), with additional ethics approval or waivers by relevant local authorities obtained by consortium members contributing data if required. The final pooled, harmonised and cleaned dataset, as well as the deidentified, renamed CXR images, is stored on a secure cloud-based server. All analyses of existing CAD products, as well as the paediatric-optimised products, will be published in peer-reviewed publications and shared with other stakeholders like the WHO and donor and procurement organisations to guide policy updates and procurement pathways to ensure widespread uptake.
This study aims to describe the characteristics of hospitalised COVID-19 patients in a tertiary care hospital close to an international airport in Japan and to compare these characteristics among different waves during the pandemic.
Retrospective observational study.
Tertiary care centre in Japan.
All patients diagnosed with COVID-19 who were hospitalised between January 2020 and April 2022 were included.
Clinical characteristics, characteristics of admission, treatments and outcomes were investigated and compared among six pandemic waves.
A total of 827 patients were included. The median age was 58.0 years. More than half of the patients (58.3%) had at least one comorbidity. The majority of patients (89.0%) were domestically infected patients admitted under the Infectious Diseases Law, while the remaining patients (11.0%) were those diagnosed during airport quarantine and admitted under the Quarantine Act. Hospital-acquired COVID-19 infection occurred in 7.0% of cases, and mainly during the sixth wave. Overall, some form of oxygen therapy, high-flow oxygen devices, invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation was provided in 46.3%, 10.4%, 4.5% and 1.5% of cases, respectively. Only 1.8% of patients were treated in the intensive care unit (ICU), and 59.5% of patients on IMV were managed in the non-ICU ward. The in-hospital mortality rate was 5.8%. Median age, percentages of some comorbidities, vaccination coverage, medications for COVID-19, types of supportive care and ICU admissions differed significantly among waves.
This study suggests that patient characteristics, vaccination coverage, standard of treatment and severity of illness changed across waves during the COVID-19 pandemic. Intensive care delivery in non-ICU wards was unavoidable due to limited ICU capacity, which may be a key consideration when preparing for future pandemics.
The aim of the study is to explore the experiences of adult relatives who cohabit with patients receiving hospital-at-home (HaH) care. The healthcare system is increasingly adopting HaH as a response to hospital overcrowding and the growing need for personalised, home-based care. While HaH has been shown to benefit patients, there is limited understanding of the impact on cohabiting relatives, who often assume a caregiving role without adequate preparation or support.
A qualitative inductive approach.
Semi-structured interviews were carried out with 10 cohabiting relatives of HaH patients from North Zealand and Denmark. Data collection took place over two periods between March 2023 and February– April 2024. Data were analysed using inductive qualitative content analysis to identify key themes in the relatives' experiences.
Relatives reported mixed feelings about HaH. While they appreciated the ability to be close to their loved ones and maintain a more normal daily routine, some felt overwhelmed by the caregiving responsibilities imposed upon them. The lack of involvement in treatment decisions, sometimes inadequate communication from healthcare professionals, and the pressure to manage both practical and emotional aspects of care were among the concerns. However, despite these challenges, relatives strongly preferred HaH over conventional hospital admissions due to the reduced disruption to their daily lives and the perceived improvement in their loved ones' well-being.
Although HaH presents additional burdens and concerns for relatives, they prefer this model of care over traditional hospitalisations. However, it is crucial that relatives are actively involved in the decision-making process and provided with adequate support to manage the caregiving responsibilities effectively. This involvement can help ensure a more positive experience for both relatives and patients, contributing to the overall success of HaH.
This study emphasises the vital role of relatives in HaH care, highlighting their preference for HaH despite the additional burden. Healthcare professionals must involve relatives in decision-making and provide adequate support to manage caregiving responsibilities. A more individualised approach can enhance the caregiving experience, reduce stress and improve patient outcomes.
This study fills a gap in understanding relatives' experiences in HaH care, stressing the need for better communication and support. By involving relatives more effectively, healthcare professionals can improve the success of HaH and reduce strain on healthcare systems.
This study adhered to the COREQ criteria.
No patient or public contribution.
Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI.
The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9–14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15–18 mg/kg/day, followed by 5–7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis.
The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.
Japan Registry of Clinical Trials (jRCTs031250067).
A comprehensive understanding of the impact of environmental noise on patient outcomes is crucial for nurses who play key roles in sound environment adjustments. However, no review has comprehensively explored these effects in hospitalized patients.
To synthesize evidence on the impact of noise on inpatient outcomes, providing a comprehensive view.
This scoping review was conducted in accordance with the Joanna Brigs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. We searched PubMed, CINAHL Plus, and the Cochrane Library for articles published in January 2024.
We identified 28 eligible articles. In the 28 articles, the most common patient outcome was sleep, followed by psychological state, physiological state, satisfaction and well-being, delirium, pain, and unplanned readmission. Further, 21 (75.0%) articles included only patients in intensive care units (ICUs), 25 (89.3%) used cross-sectional analysis, and only 13 (46.4%) performed multivariable analysis adjusted for confounding factors. In the 13 articles that used multivariable analysis, noise was associated with decreased sleep quantity and quality in both ICU and ward patients, increased delirium risk in ICU patients, increased risk of readmission within 30 and 90 days after hospital discharge, increased heart and respiratory rates in ICU patients, and increased anxiety in ICU patients.
Nurses need to pay more attention to the negative impact of noise on inpatient outcomes. The findings of this study would promote the comprehensive understanding of nurses on noise impact on inpatient outcomes and their commitment to noise reduction in hospital environments.
FreshRSS 