Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity, with frequent exacerbations resulting in hospitalizations, increased healthcare burdens, and mortality. The GOLD report emphasizes dual or triple inhaler therapy for high-risk (GOLD group E) patients, yet real-world guideline adherence during hospitalization remains unclear. This study aimed to evaluate concordance with GOLD-recommended maintenance inhaler therapy at hospital discharge in patients with severe exacerbations of COPD and to identify factors associated with treatment rates.

We conducted a retrospective, multicentre, observational study of 3928 COPD inpatients across 85 hospitals within the German Helios group (January 2022-September 2024). The primary outcome was the proportion of patients discharged on GOLD-concordant inhaler therapy, defined as dual long-acting bronchodilation (LABA/LAMA), or triple therapy (LABA/LAMA/ICS) in patients with eosinophils ≥300/μL or high exacerbation risk. Secondary outcomes included diagnostic procedures, pharmacological management, hospital characteristics, in-hospital outcomes and predictors of guideline-concordant prescribing assessed using multivariable logistic regression models.

The mean age of the cohort was 70.1 years (SD 10.1), 45% (n = 1784) were female, 75% (n = 2952) had cardiovascular comorbidities and 45% were treated on pneumology wards. Eosinophil counts were measured in 49% (n = 1895) of patients. During hospitalisation, 14% (n = 560) of patients required intensive care, mean length of stay was 6.6 days, and in-hospital mortality was 1.7% (n = 66). In patients with available documentation, at admission, 61% (1344 of 2205) received dual (21%; 455) or triple (40%; 889) maintenance inhaler therapy. At discharge, 77% (2573 of 3326) of patients were prescribed GOLD-concordant inhaler therapy (dual: 28%; 939 and triple: 52%; 1720). In multivariable analyses, guideline-concordant prescribing at discharge was independently associated with longer length of stay (odds ratio [OR] 1.17/day; 95% CI 1.06-1.29), male sex (OR 1.45; CI 1.23-1.71), treatment on a pneumology ward (OR 1.77; 1.42-2.20), and older age (OR 0.87 per standard deviation increase; CI 0.79-0.95).

In this multicentric large, real-world, hospital-based cohort of patients with severe COPD exacerbations, more than one in five patients were discharged without guideline-concordant maintenance inhaler therapy. Specialist pneumological care and structured inpatient management were strongly associated with improved adherence. Hospital care substantially increased maintenance therapy rate. Systematic implementation of eosinophil risk stratification, enhanced specialist involvement, and standardised discharge pathways could be opportunities and may substantially improve evidence-based COPD care and reduce future exacerbation risk.

This study and the preparation of the manuscript were financially supported by AstraZeneca.

Myocardial fibrosis (MF) is a pathophysiological process characterized by the excessive deposition of collagen fibers in the myocardium. Numerous studies are now dedicated to clarifying the genetic, cellular, and molecular mechanisms that drive these pathological alterations. Furthermore, substantial evidence suggests that diffuse fibrosis causes irreversible damage to the heart. Myocardial fibrosis and cardiovascular disease are interrelated, influencing each other significantly. However, the existing evidence linking myocardial fibrosis to common diseases is still insufficient. In this review, we summarized the common mechanisms underlying myocardial fibrosis and their associations with prevalent cardiovascular diseases (e.g., myocardial infarction, heart failure, hypertrophic cardiomyopathy, dilated cardiomyopathy), and emphasized the heterogeneous presentations of myocardial fibrosis across different diseases to promote the future realization of personalized treatment for fibrosis-related cardiovascular diseases.

Malnutrition is known to worsen outcomes in many diseases. This study explored its effect on prognosis in critically ill patients with atrial fibrillation (AF).

A total of 4,564 patients were studied. Their nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), and they were divided into four groups based on GNRI quartiles, with a median of 100.23 and interquartile range of 90.31-111.27. The primary outcome was 28-day mortality. Kaplan-Meier analysis evaluated survival differences among the GNRI groups, and a multivariate Cox model assessed GNRI's independent effect on mortality risk. A restricted cubic spline (RCS) analysis explored potential non-linear associations between GNRI and 28-day mortality.

There is a negative correlation between GNRI and 28-day mortality, a finding supported by a log-rank test result with p < 0.001. According to the multivariate analysis, higher GNRI values were independently associated with a lower risk of 28-day mortality (quartile 4 compared to quartile 1, the hazard ratio (HR) was 0.78 with a 95% confidence interval (CI) of 0.62-0.97, and p = 0.029). Subgroup analysis showed no association in those with obesity, or in cardiovascular ICUs or post-cardiac surgery settings. No link was found in patients with a history of AF or on CRRT. However, the association was consistently seen in septic patients with new-onset AF. Additionally, the RCS analysis revealed a non-linear relationship between GNRI and 28-day mortality, showing that as GNRI increased, the risk of 28-day mortality decreased among patients. Findings from external validation cohorts also confirm this relationship.

Among critically ill patients, elevated GNRI scores are associated with improved outcomes in patients with new-onset AF, but this association is not present in patients with preexisting AF. In the subgroup of septic patients with new-onset AF, GNRI may not reliably predict clinical prognosis, emphasizing the need for further validation prior to clinical use. The GNRI provides a straightforward, unbiased assessment of both nutritional status and systemic inflammation burden.

Discharge from psychiatric hospitalisation is associated with increased mortality risk, but risk estimates across fine-grained post-discharge intervals and identified risk factors are lacking.

We conducted a population-based study utilising a medical health record database of public healthcare services in Hong Kong. We identified all individuals aged ≥12 years who had been discharged from psychiatric inpatient units between January-01-2006 and December-31-2021. Individuals without history of psychiatric hospitalisation attending primary care clinics during the same period served as comparison group (i.e., primary-care clinics [PCC] cohort). Survival analyses estimated cumulative incidences and hazard ratios (HRs) for all-cause, natural-cause and external-cause mortality across discrete intervals from ≤1 month to >10 years post-discharge. Risk factors for excess mortality 1-year and 10-year post-discharge were evaluated.

The discharged cohort comprised 114,395 patients with 975,229 controls. Within the first-year post-discharge, within the deceased patient group, natural causes and suicide-related mortality accounted for 65.8% and 18.8% of deaths in the discharged cohort, and for 87.8% and 1.6% of deaths in the PCC cohort. The relative proportion of all deaths due to suicide in the discharged cohort decreased from 18.8% at 1-year to 11.7% at 10-year, while the relative proportion of all deaths from natural causes increased from 65.8% at 1-year to 73.3% at 10-year. Respiratory diseases (year 1 = 30.6%, year 10 = 35.0%) and cardiovascular diseases (year 1 = 10.7%, year 10 = 11.0%) were consistently leading causes of natural deaths. Relative all-cause mortality risk peaked within 1-month post-discharge (HR = 10.31 [95% confidence interval (CI) = 9.36-11.36]), remaining high at 1-year (HR = 3.40 [95% CI = 3.17-3.65]) and 10-year (HR = 2.61 [95% CI = 2.52-2.69]). External-cause mortality, particularly suicide-related mortality, showed extremely high risk during 1-month (HR = 78.54 [95% CI = 52.64-117.18]), and remained high at 1-year (HR = 42.40 [95% CI = 30.02-59.87]) and 10-year (HR = 10.29 [95% CI = 8.75-12.10]). Depression diagnosis at discharge conferred the highest short-term suicide risk, while substance/alcohol use disorders showed the highest long-term any-cause mortality risk. Risk factors for premature mortality within 1-year and 10-year post-discharge included male sex, old age, not receiving social/disability allowance, greater physical morbidity burden, self-harm history, and poor discharge psychiatric status. Ethnicity data were not available in the database.

The immediate post-discharge phase is a critical window for targeted and diagnosis-specific intervention, including psychiatric/social/financial support. Future research should prioritise the development of robust risk prediction models that incorporate key risk factors identified to facilitate personalised care and improves post-discharge outcomes for high-risk individuals.

Health and Medical Research Fund.

Vascular calcification (VC) is a major determinant of cardiovascular mortality in patients undergoing maintenance hemodialysis (MHD). Although physical activity (PA) is associated with attenuated VC, the precise mechanisms underlying this association, particularly in the MHD population, remain unclear. Irisin, a myokine linked to PA and VC inhibition, is a potential mediator. However, its role in translating PA benefits to reduced VC in MHD patients is unknown.

This cross-sectional study enrolled 326 patients undergoing maintenance hemodialysis at Xuanwu Hospital Capital Medical University (2020-2023). PA volume was assessed using the International Physical Activity Questionnaire. Serum irisin levels were measured by enzyme-linked immunosorbent assay. Severe VC was defined as an abdominal aortic calcification score (AAC) ≥ 6 on lateral lumbar spine radiography. Multivariable logistic regression and restricted cubic spline models examined the independent and nonlinear associations of PA and irisin with severe VC. Causal mediation analysis estimated the proportion of the PA-VC association mediated by irisin.

Among 326 patients, those in the severe VC group (n=196) exhibited significantly lower PA levels and serum irisin compared to the non-severe group (n=130). In fully adjusted models, both higher PA (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34-0.74) and higher irisin (OR, 0.56; 95% CI, 0.37-0.83) were independently associated with lower odds of severe calcification, with significant inverse dose-response trends (P for trend <0.001). Restricted cubic spline analyses revealed a significant nonlinear relationship between irisin and calcification risk (P for nonlinearity = 0.009), while the association for PA suggested a potential plateau at higher activity volumes. These inverse associations were consistent across subgroups stratified by age, gender, Body mass index (BMI), and diabetes status (all interaction P > 0.05). Mediation analysis indicated that irisin mediated approximately 60.8% of the total association between PA and severe VC.

This study identifies independent links between physical activity, higher irisin levels, and lower severe vascular calcification risk in hemodialysis patients, with irisin mediating a major part of this association. These findings point to the importance of lifestyle and myokine pathways. Further longitudinal and interventional research is needed to confirm causality and underlying mechanisms.

Cardiovascular inflammation is increasingly recognized not merely as a secondary response to hemodynamic or metabolic injury, but as a determinant of disease initiation, progression, and remodeling. In the injured heart and vasculature, danger sensing, inflammatory priming, inflammasome activation, nucleic acid recognition, immunometabolic rewiring, immunothrombosis, adaptive immune remodeling, and defective resolution form interdependent circuits rather than isolated pathways. A key challenge is to understand how these circuits shift from adaptive clearance and repair to persistent immune activation, fibrosis, and functional decline. Here, we synthesize evidence on immune landscapes and core inflammatory networks in cardiovascular diseases, focusing on TLR-NF-κB signaling, NLRP3 inflammasomes, cGAS-STING-dependent cytosolic DNA sensing, alternative mitochondrial nucleic acid-sensing platforms, and redox-immunometabolic gating. We highlight mitochondrial quality control and mitochondria-derived DAMPs, including mtDNA, mtROS, ATP, cardiolipin, and oxidized lipids, as an upstream interface linking metabolic stress to sterile immune activation. We further organize disease-specific inflammatory patterns through a stage-cell-threshold perspective across ischemic injury, vascular and metabolic disease, and cardiomyopathic remodeling. Finally, we discuss network-guided therapeutic strategies, translational limitations, biomarkers, endpoints, and safety considerations. This integrated perspective provides a conceptual basis for moving cardiovascular inflammatory therapy from broad suppression toward more precise network regulation.

Mild cognitive impairment (MCI) is characterized by a decline in cognitive functions while the ability to perform daily activities remains intact. This pathological condition is a recognized as risk factor for dementia-related disorders, and the current lack of therapies is the critical issue. Our preclinical studies indicated that a formulation (named GeNeurofil™) exhibited a synergistic neuroprotective effect in an animal model of amyloid beta toxicity. Therefore, the present study aimed to evaluate the efficacy of GeNeurofil™ in patients with mild cognitive impairment.

A six-months, randomized, double-blind, placebo-controlled pilot trial (retrospectively registered on ISRCTN registry-number ISRCTN11405046-01/07/2026) was performed enrolling 54 patients with mild to moderate MCI (Clinical Dementia Rating Scale ranging from 0.5 to 2). Patients, concurrently maintained under their usual medications, received either the GeNeurofil™ (0.7 mL × 3/day) or an identical placebo (0.7 mL × 3/day) for six months. The psychometric assessments were performed using the Mini Mental State Examination (MMSE) tests and depressive symptoms were evaluated with the Zung Test. Plasma samples were analyzed for NfL and p-TAU.

After six months of treatment, GeNeurofil™ supplementation improved CDR, MMSE, and Zung scores. Furthermore, the treatment reduced plasmatic levels of light neurofilaments (NfL) and phosphorylated Tau protein (p-TAU) compared to placebo.

Our findings indicate that six months of supplementation with GeNeurofil^TM might represent a helpful adjuvant strategy for cognitive impairment. GeNeurofil™ nutraceutical supplementation demonstrates a favorable safety profile, however given the exploratory nature of this pilot feasibility trial, these preliminary findings will further followed by confirming definitive clinical efficacy in larger clinical trials.

We need to understand therapists' experiences of delivering manual-based psychotherapies to identify possible dissemination barriers and opportunities. This study explored therapists' experiences of delivering CBT-AN-20, a new 20-session cognitive-behavioral intervention for outpatients with anorexia nervosa.

Ten therapists who had delivered CBT-AN-20 to at least one patient participated in an online survey. We used descriptive statistics (Likert-scale questions; demographics) and thematic analysis (open-ended text) to analyze responses. Pre-registration: https://doi.org/10.17605/OSF.IO/R2U8P.

Therapists' mixed experiences of CBT-AN-20 were evident across quantitative and qualitative responses. Thematic analysis generated three main themes: Feelings about therapy over time; beliefs about for whom therapy might work; and perceptions of the characteristics of therapy. Despite some initial uncertainty, therapists reported both positive and negative experiences of delivering CBT-AN-20. They felt it worked well for some patients (highly motivated/less complex eating disorder presentations) but not for others (less motivated/more complex presentations). They experienced CBT-AN-20 as fast-paced and action-packed, yet with a clear, supportive structure. Therapists found encouraging rapid, early changes to patients' eating and weight difficult but worthwhile.

CBT-AN-20 is feasible and broadly acceptable for therapists to deliver. Therapists' mixed feelings were like those reported in qualitative studies of other psychotherapies for anorexia nervosa. While the manual addresses many identified challenges, training and supervision should focus on bolstering therapists' confidence in delivering CBT-AN-20 with fidelity. Future research should explore whether therapists' perceptions of CBT-AN-20 change with experience and if their expectations about whom CBT-AN-20 might work for are accurate.

This narrative review examines post-traumatic stress disorder (PTSD) and other trauma- and stressor-related mental health disorders in elite athletes. Elite athletes may experience these disorders at higher rates than the general population owing to disproportionate exposure to traumas and stressors, which can be experienced at individual and collective levels. These disorders can be difficult to detect due to complex symptom presentations and coping strategies that may mask symptoms. They can have both psychological and somatic components, and this dual nature has significant relevance for elite athletes given sport demands. Early identification of elite athletes suffering from trauma- and stressor-related symptoms may prevent progression to PTSD and other chronic mental health disorders. Cultural considerations specific to trauma require attention, as athletes' diverse cultural backgrounds shape help-seeking behaviours, symptom expression, stigma and access to care. Within a framework of trauma-informed care, first-line psychotherapies are generally cognitive-behavioural therapy-based, and first-line pharmacological treatments are generally serotonergic antidepressants. Team-based interventions may be necessary if there is a vicarious aspect to traumas or stressors. Future needs for the field include study and implementation of coordinated approaches to trauma screening and trauma- and stressor-related symptom screening for elite athletes. Healthcare providers and other entourage members for elite athletes should receive education on trauma-informed approaches. Organisational supports should facilitate implementation of trauma-informed care. Further research is needed on all types of traumas and stressors and particularly on institutional and systemic maltreatment as well as on established and emerging therapies as uniquely applied to elite athletes.

Professional psychological help-seeking attitudes are crucial for addressing mental health challenges, yet the mechanisms underlying their improvement through internet-based interventions remain poorly understood.

This randomized controlled trial aimed to (1) evaluate the efficacy of Internet-based Acceptance and Commitment Therapy (iACT) in enhancing professional help-seeking attitudes, and (2) elucidate the longitudinal mediating roles of psychological rigidity and self-stigma.

A total of 91 male participants (Mean Age = 21.09) were randomly assigned to either a 12-day iACT intervention group (n = 46) using a self-developed mobile application or a waitlist control group (n = 45). Psychological flexibility, rigidity, self-stigma, and help-seeking attitudes were measured at four time points: baseline, mid-intervention (Day 6), post-intervention (Day 12), and 1-month follow-up. Data were analyzed using repeated-measures ANOVA and latent growth modeling.

Intention-to-treat analysis revealed the iACT group showed greater improvements in help-seeking attitudes than controls (F (3,87) = 5.95, p < 0.001), with medium-to-large between-group effects at post-test for reducing psychological rigidity (d = -0.77, 95% CI [-1.19, -0.34]) and self-stigma (d = -0.88, 95% CI [-1.31, -0.45]). Latent growth modeling revealed a sequential mediation effect: the iACT intervention reduced psychological rigidity (β = -0.53, SE = 0.12), which in turn reduced self-stigma (β = 0.61, SE = 0.09) and improved help-seeking attitudes (β = 0.47, SE = 0.08).

This study provides the first evidence that a self-guided iACT mobile intervention can effectively enhance professional help-seeking attitudes by reducing psychological rigidity, which in turn alleviates self-stigma. The developed app offers a scalable solution to overcoming stigma-related barriers to mental health care.