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ADAMTS13 as a thromboinflammatory brake at the vascular-immune interface: from viral immunothrombosis to the tumor microenvironment.1 week agoADAMTS13 is conventionally regarded as the protease whose severe deficiency causes thrombotic thrombocytopenic purpura (TTP). By cleaving shear-unfolded ultra-large and high-molecular-weight von Willebrand factor (VWF), ADAMTS13 limits a platelet- and leukocyte-adhesive vascular scaffold. We propose a narrower and testable extension of this biology to cancer: an imbalance between VWF burden and ADAMTS13 processing capacity may act as a context-dependent modifier or amplifier of thromboinflammation in selected VWF-rich, shear-exposed tumor vascular niches, but is not established as an initiating or universally rate-limiting cause of cancer-associated thrombosis. We define "relative ADAMTS13 insufficiency" as a research phenotype rather than a diagnosis or evidence of causality. It refers to ADAMTS13 activity outside the severe-deficiency range, typically ≥10%, together with increased VWF burden and a disproportionately low ADAMTS13 activity/VWF antigen ratio (ADAMTS13:Act/VWF: Ag). This phenotype is mechanistically nonspecific and may reflect increased VWF release, impaired whole-molecule VWF clearance, reduced ADAMTS13 production, stability, or availability, functional inhibition of proteolysis, reduced VWF susceptibility to cleavage, or shared upstream inflammation. Human evidence from COVID-19 and cancer remains predominantly associative, whereas tumor-relevant perturbation studies provide preclinical causal support in defined models. The causal importance of the VWF-ADAMTS13 axis in human tumors nevertheless remains unproven. We therefore position this module within a broader thromboinflammatory network that includes complement activation, neutrophil extracellular traps, platelet activation, and tissue factor-thrombin-fibrin pathways. ICI-associated endothelial phenotypes are distinguished from rare ICI-associated immune TTP with categorical severe ADAMTS13 deficiency. Candidate interventions are accordingly presented as mechanistic research nodes requiring staged validation rather than as established oncology therapies.CancerChronic respiratory diseaseCardiovascular diseasesAccess
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Dual-targeted nanotechnology for gynaecological cancers: a comprehensive review of mechanisms and clinical potential.1 week agoOvarian, cervical and endometrial cancers have been the leading cause of morbidity and mortality in women, often resulting from late diagnosis, resistance to therapies and off-target toxicity of conventional therapies.
The review discusses recent progress in the development of dual-targeted nanocarrier systems in gynaecologic oncology, relying on peer-reviewed publications in scientific databases published within the past decade. Applications of these systems are also discussed in terms of the potential to improve the selectivity and therapeutic efficiency of tumour therapy. Major available evidence is based on preclinical in vitro and in vivo models. Clinical translation is in its early-phase trials, suggesting clinical validation in gynaecologic oncology remains in its infancy. The most important challenges in translation are scalable manufacturing, long-term safety, biological complexity and regulatory challenges.
This review describes the prevailing situation and constraints of dual-targeted nanotechnology, focusing on possible applications in the development of more accurate and individualized therapies for gynaecologic cancers.CancerCare/Management -
Repeated remimazolam sedation for interstitial brachytherapy in cervical cancer: a randomized controlled trial.1 week agoEvidence regarding repeated remimazolam administration remains limited. We hypothesized that remimazolam would be associated with fewer adverse events than propofol while maintaining stable sedative requirements across three repeated sedation sessions.
Patients with cervical cancer undergoing three fractions of interstitial brachytherapy were randomized to propofol or remimazolam. The primary outcome was the proportion of sedation episodes with at least one prespecified intraoperative adverse event across three sessions. Secondary outcomes included sedative dose, hemodynamics, and sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS).
A total of 100 participants were randomized, of whom 91 completed all three prespecified sedation sessions and were included in the primary per-protocol analysis (46 in the propofol group and 45 in the remimazolam group). Across 138 propofol and 135 remimazolam episodes, overall adverse events were less frequent with remimazolam (17.78% vs. 59.42%; RR, 0.30; 95% CI, 0.18-0.49; p < 0.001). Respiratory depression (3.70% vs. 26.09%; RR, 0.14; 95% CI, 0.04-0.53; p = 0.004) and hypotension (8.15% vs. 41.30%; RR, 0.20; 95% CI, 0.09-0.42; p < 0.001) were also lower with remimazolam. Remimazolam requirements remained stable across sessions (third vs. first: mean difference, 0.19 mg; 95% CI, -0.78 to 1.15; p = 0.846). No significant between-group differences were observed in PSQI or AIS scores.
Across three consecutive sedation sessions for interstitial brachytherapy, remimazolam was associated with fewer respiratory and hemodynamic adverse events than propofol, while sedative requirements remained stable across the three sessions.
Chinese Clinical Trial Registry (identifier: ChiCTR2500108294).CancerCare/Management -
Improved Predictive Capacity of SARS-CoV-2 Seroconversion Using a Model Based on Torque Teno Virus Viral Load.1 week agoKidney transplant patients (KTPs) exhibit markedly reduced seroconversion rates following SARS-CoV-2 vaccination due to chronic immunosuppression. Torque Teno virus (TTV) viral load has been proposed as a biomarker of immune competence.
To determine the seroconversion rate to SARS-CoV-2 vaccination in KTPs and to develop a predictive model based on TTV viral load.
A prospective observational cohort study was conducted in adult KTPs with complete SARS-CoV-2 vaccination scheme. Anti-Spike IgG antibodies were quantified. TTV viral load was quantified by qPCR. Logistic regression models were developed using TTV viral load alone and with patients' variables (expanded model). Model performance was assessed using receiver operating characteristic analysis and internal validation.
Seroconversion rate was 16.9% after complete vaccination, 21.9% after one booster and 55.5% after two boosters. TTV viral load alone showed modest predictive capacity for seroconversion (AUC = 0.634). The expanded model significantly improved prediction capacity (AUC = 0.814) with a NPV of 90.0%.
Pre-vaccination TTV viral load alone is insufficient to predict seroconversion to SARS-CoV-2 vaccination in KTPs. The expanded model improved this predictive capacity when combined with clinical and vaccine related variables reflecting the multifactorial nature of immune competence. Integrative predictive approaches may help optimize vaccination strategies in immunocompromised populations.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Longitudinal Impact of Pseudomonas aeruginosa Versus Haemophilus influenzae Colonization on Lung Function Decline in Children With Primary Ciliary Dyskinesia.1 week agoThe association of Pseudomonas aeruginosa (PsA) and Haemophilus influenzae (HI) colonization with lung function in children with primary ciliary dyskinesia (PCD) remains insufficiently defined. We aimed to compare spirometric parameters between PsA- and HI-colonized children and evaluate longitudinal changes before, at, and after chronic colonization.
This retrospective cohort included patients aged ≥ 5 years with definite or highly probable PCD and chronic PsA or HI colonization. Chronic colonization was defined using repeated sputum cultures over 12 months. Pulmonary function tests were analyzed 1 year before colonization, at colonization, and 1 year after colonization. FEV1, FVC, and FEF25-75 were reported as percent-predicted values and GLI 2012 z-scores. Individual pre-to-after-colonization change scores and bronchiectasis subgroup analyses were performed.
Among 290 patients with PCD, 40 met inclusion criteria: 10 with PsA and 30 with HI colonization. PsA-colonized patients were older at colonization than HI-colonized patients (17 [12-23] vs. 11 [9-15] years, p = 0.011), and bronchiectasis was more frequent in the PsA group (100% vs. 60%, p = 0.019). PsA colonization was associated with lower lung function across several spirometric measures. Both groups showed significant within-group declines in FEV1 and FEF25-75 over time. However, individual pre-to-after-colonization changes in FEV1 and FEF25-75 z-scores did not differ significantly between groups, including in the bronchiectasis subgroup analysis.
PsA colonization was associated with lower lung function than HI colonization, but not with significantly greater longitudinal decline. These findings suggest that PsA may mark more advanced disease rather than independently accelerating functional loss. Larger prospective studies with non-colonized comparators are needed.Chronic respiratory diseaseCardiovascular diseasesAccessAdvocacy -
Beyond Snoring, Sleepiness and Surgery: Update on the Prevalent Symptoms of and Treatment Effects in all Age Groups With Pediatric Obstructive Sleep Apnea.1 week agoScreening and treatments for pediatric obstructive sleep apnea (pOSA) often use adult symptoms and conventional surgical approaches. This study tested the hypothesis that symptoms and treatment efficacy for OSA differ across age groups.
Single-center cohort study of 0 to 18-year-olds who were managed and underwent polysomnography (PSG) in a pediatric-dedicated sleep medicine center from 2020 to 2024.
Of 491 children, 489 had pOSA, 57.7% were male, the median age was 6 years old (IQR1-3, 4-9), and 41% already had an adeno- or adenotonsillectomy prior to the PSG. Only 15.6% were obese, and 13.2% had an Epworth Sleepiness Score over 10. Snoring was not the most prevalent nocturnal symptom: restlessness (91.6%), chronic insomnia (86.1%), kicking legs (82.0%), and frequent awakening (78.4%) were all more common. Neurocognitive issues, present in 93.7%, were most commonly mood swings (86.5%) and ADHD (51.9%). Of the 270 without surgery before the PSG, 72.2% (n = 195) were referred, and 173 had surgery. Positive airway pressure (PAP) was prescribed for 240 (49.1%) patients, 176 (73%) of whom had enough CPAP usage to provide machine-estimated apnea-hypopnea index (AHI). After adenotonsillectomy, 27.0% had a post-operative AHI under 5 events per hour, and 73.1% had improvement in neurocognitive issues while that was 94.9% and 87.2% in those using PAP, respectively. After adjusting for age and AHI, PAP had threefold (aOR 3.85, 95%CI 1.39-10.67) higher odds of improving neurocognitive issues than surgery, p = 0.010.
The majority of children with pOSA are not tired or obese. Insomnia and restless sleep are more common than snoring. Daytime neurocognitive issues affect almost all children with pOSA and improve with treatment, especially PAP.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Validation of the behavioural and social drivers of influenza vaccine survey in Australia: Cognitive interviews and psychometric evaluation.1 week agoSeasonal influenza vaccination reduces the risk of contracting influenza. In Australia, vaccination coverage is consistently low among the most at-risk groups eligible for the free influenza vaccine. To establish an annual national monitoring of the behavioral and social drivers of influenza vaccination, we validated the World Health Organization's Behavioral and Social Drivers of Influenza Vaccination survey. Ours is the first study reporting the validation results of the newly developed survey tool. Two validation stages occurred: first, cognitive interviews and survey item revisions based on feedback; second, collecting quantitative data, performing psychometric analysis, including factor analysis, and assessing the association between survey items and influenza vaccination intention using polychoric correlation and a random forest model to determine each item's importance. We modified nine of the 31 survey items based on cognitive interviews with 16 adults. Based on the psychometric evaluation of 2055 respondents, we identified and validated five factors that underlie the survey structure and aligned well with the four domains of the BeSD framework: Thinking and Feeling, Social Processes, Motivation, and Practical Issues. Each item correlated with the intention to receive influenza vaccine, particularly those related to perceived vaccine importance and social responsibility. We recommend further validation in various contexts, especially to assess the survey's predictive validity regarding actual vaccination uptake.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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Construction and multi-center validation of a model based on blending ensemble learning for predicting stroke-associated pneumonia following acute ischemic stroke.1 week agoStroke-associated pneumonia (SAP) is a common and serious infectious complication following acute ischemic stroke (AIS), leading to worsened clinical outcomes. We aimed to develop and validate a novel predictive model based on Blending Ensemble Learning, to enable early, precise screening and individualized risk stratification for SAP.
In this multi-center study, a derivation cohort was initially established using 1,123 patients admitted between 2022 and 2024. Subsequently, 199 patients were prospectively enrolled in early 2025 as a temporal validation set, and 287 patients were extracted from a regional health big data platform (covering 12 hospitals) to serve as an external validation set. High-value clinical and biomarker features were identified via least absolute shrinkage and selection operator (LASSO) regression. To overcome the limitations of single classifiers, a Blending Ensemble Learning strategy was adopted to construct the final predictive model. The model underwent comprehensive evaluation for discrimination, calibration, and clinical utility, and was benchmarked against single random forest (RF) and extreme gradient boosting (XGBoost) models.
Seventeen predictors were identified, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), the National Institutes of Health Stroke Scale (NIHSS), and D-dimer. The Blending ensemble model demonstrated superior discrimination in the validation cohort, achieving an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.898 (95% CI: 0.845-0.951), which significantly outperformed the optimal single model. Furthermore, SHapley Additive exPlanations (SHAP) analysis highlighted hyperinflammation, immunothrombosis, and nutritional depletion as pivotal mechanisms driving SAP pathogenesis.
The proposed Blending ensemble model exhibits excellent generalizability and high sensitivity. The accompanying web-based tool provides robust decision support for identifying high-risk patients and implementing early precision interventions.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy -
European society for organ transplantation clinical practice guideline on prevention and treatment of chronic lung allograft dysfunction.1 week agoChronic lung allograft dysfunction (CLAD) is the primary cause of late graft loss after lung transplantation, affecting up to half of lung transplant recipients within 5 years and presenting with heterogeneous phenotypes, most commonly bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome. Prevention and treatment of CLAD are challenging. This European Society for Organ Transplantation (ESOT) clinical practice guideline was developed by a multidisciplinary Task Force, including patient and allied healthcare representation, using systematic reviews and GRADE methodology. Eight key PICO questions addressing prevention and treatment of CLAD were evaluated. In terms of prevention, recommendations are in favor of using tacrolimus over cyclosporine, either mycophenolate or azathioprine, and azithromycin to reduce the risk of CLAD. Regarding treatment, montelukast could be considered in early-stage BOS. Current data are inconclusive in demonstrating benefits of anti-thymocyte globulin, alemtuzumab or extracorporeal photopheresis compared with standard of care, and do not support the use of antifibrotics in BOS. The Task Force emphasizes the urgent need for high-quality clinical trials and standardized care pathways in CLAD management.Chronic respiratory diseaseCare/Management
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Readiness for Hospital Discharge and Quality of Life Among Patients Undergoing Surgery for Type A Aortic Dissection: A Prospective Observational Cohort Study.1 week agoTo examine the level and associated factors of readiness for hospital discharge among patients undergoing surgery for type A aortic dissection, and its correlations with quality of life at 30 and 90 days post-discharge.
A prospective observational cohort study with a cross-sectional baseline assessment and longitudinal follow-up at 30 and 90 days post-discharge.
This study employed a convenience sampling method to recruit 186 patients who underwent surgery for type A aortic dissection at the Department of Cardiovascular Surgery of a tertiary hospital in northern China between January 2024 and June 2025. Baseline data were collected within 24 h before discharge using the Readiness for Hospital Discharge Scale, the All Aspects of Health Literacy Scale, the Perceived Social Support Scale, and the Quality of Discharge Teaching Scale. Quality of life was assessed 30 and 90 days after discharge using the 8-item Short Form Health Survey. Descriptive statistics, correlation analysis, and multiple linear regression analysis (enter method) were used to analyse the data.
A total of 186 patients completed baseline assessment (184 at 30 days; 180 at 90 days). The mean readiness for hospital discharge score was 153.74 ± 31.85, with a mean item score of 6.99 ± 1.45, indicating low readiness. Multiple linear regression analysis revealed that quality of discharge teaching, social support, health literacy, and having a college degree or above were the main associated factors of readiness for hospital discharge. Together, these associated factors accounted for 30.0% of the total variance. Spearman's correlation analysis revealed positive correlations between readiness for hospital discharge and quality of life at 30 and 90 days.
Patients undergoing surgery for type A aortic dissection have low readiness for hospital discharge, which is associated with quality of discharge teaching, social support, health literacy, and educational level. Greater readiness was associated with better quality of life at 30 and 90 days post-discharge.
Nurses should assess discharge readiness and provide targeted transitional care, particularly for patients with lower education, limited health literacy, or insufficient social support. Future intervention studies are needed to test whether enhancing readiness improves outcomes.
This study adhered to the STROBE reporting guidelines.
No patient or public contribution.Cardiovascular diseasesAccessCare/ManagementAdvocacy