• Primary Vulvar HPV-independent Adenosquamous Carcinoma: A Case Series of a Rare Neoplasm With an Apparent Predilection for the Upper Vulva.
    4 days ago
    Adenosquamous carcinoma is a rare malignancy described in a variety of body sites, including the uterine cervix. These tumors exhibit morphologically unequivocal areas of squamous and glandular differentiation and are typically associated with an aggressive clinical course. Primary adenosquamous carcinoma of the vulva, arising outside the Bartholin gland, has only been described in a few case reports, is poorly characterized and is currently not included in the 5th Edition WHO Classification of Female Genital Tumours. We report a series of 3 primary vulvar HPV-independent adenosquamous carcinomas, all arising in the upper vulva close to the junction with the vagina, in close proximity to the urethral meatus. All tumors showed surface ulceration, and there were no features of lichen sclerosus or vulvar intraepithelial neoplasia in the adjacent squamous epithelium. The squamous components ranged from 40% to 70% of the neoplasms. All tumors exhibited mutation-type p53 expression and negative/non-block-type staining for p16. Molecular testing confirmed a TP53 mutation in all tumors and showed an additional AMER1 mutation in one. Two patients presented with lymph node metastasis at the time of diagnosis or shortly thereafter. None of the patients died of their disease, with follow-up ranging from 2 to 81 mo. Our findings suggest that primary vulvar HPV-independent adenosquamous carcinoma is a distinct morphologic entity that warrants inclusion in future classifications of primary vulvar neoplasms.
    Cancer
    Care/Management
  • Direct Tumor Suppression by Anti-Basigin Antibody and Enhancement of Macrophage-Mediated Cancer Cell Phagocytosis under SIRPα Blockade.
    4 days ago
    The transmembrane protein CD47 expressed on tumor cells suppresses Fcγ receptor-mediated antibody-dependent cellular phagocytosis (ADCP) through its interaction with signal regulatory protein α (SIRPα), a transmembrane protein expressed on phagocytic cells such as macrophages. Although blockade of the CD47-SIRPα interaction enhances the efficacy of tumor-targeting antibodies such as rituximab, its antitumor activity remains limited in cancers lacking defined tumor-associated antigens. In this study, we identified the membrane protein Basigin and SIRPα as broadly applicable therapeutic targets for cancer. We found that the 8H4 antibody, originally identified in the course of other research, recognized mouse Basigin, suppressed proliferation of diverse cancer cell types, and induced cancer cell death. Treatment with the 8H4 antibody indeed inhibited tumor growth in vivo. Moreover, combined treatment with the 8H4 antibody and an anti-SIRPα antibody that blocks the CD47-SIRPα interaction markedly enhanced macrophage-mediated ADCP against diverse cancer cell types in vitro. These results suggest that targeting Basigin, particularly in combination with SIRPα blockade, may provide a basis for the development of macrophage-mediated immunotherapies applicable to cancers in which tumor-associated antigens have not yet been identified.
    Cancer
    Policy
  • Postpandemic Trends in Pediatric Respiratory Virus Hospitalizations: A Multicenter Study, 2019-2025.
    4 days ago
    The COVID-19 pandemic profoundly altered the circulation of respiratory viruses in children, changing the epidemiology of acute lower respiratory tract infections. In the postpandemic period, respiratory pathogens showed marked temporal variability. The 2024-2025 season was the first respiratory syncytial virus (RSV) season in Italy during which RSV immunoprophylaxis with nirsevimab was implemented, allowing evaluation of recent trends in pediatric hospitalizations.

    We conducted a retrospective multicenter study across 16 pediatric hospitals in Italy. Hospitalizations of children younger than 18 years with RSV, influenza, adenovirus, parainfluenza virus, rhinovirus infection, or bronchiolitis of unspecified viral etiology were identified from January 2019 to March 2025 using ICD-9-CM diagnostic codes. Annual and monthly hospitalization rates per 100,000 children were calculated using national demographic data. Temporal trends were assessed across six consecutive seasons.

    Overall, 23,981 hospitalizations were recorded. RSV was the most frequent pathogen (42.5%), followed by influenza (18.6%), adenovirus (9.9%), and rhinovirus (7.3%). Hospitalizations declined sharply in 2020 and subsequently increased, peaking in 2024 (n = 4903; +30.8% vs. 2022). During the 2024-2025 season, total admissions decreased by 17.2% compared with 2023-2024 (3390 vs. 4095), mainly due to a marked reduction in RSV-related hospitalizations (-41.6%, 1230 vs. 2107), with modest increases in influenza-, adenovirus-, and rhinovirus-associated admissions.

    This nationwide analysis describes postpandemic trends in pediatric respiratory virus hospitalizations in Italy, highlighting changing pathogen-specific patterns and the need for continued viral surveillance.
    Chronic respiratory disease
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  • Mortality and risk factors associated with death in patients with obesity hypoventilation syndrome and of predominantly Afro-Caribbean origin in Martinique.
    4 days ago
    Obesity hypoventilation syndrome (OHS) is a respiratory complication of obesity. Mortality from OHS is non-negligible. Risk factors for OHS-related mortality are not well established and vary in the literature. This study aimed to assess mortality from OHS in patients in Martinique and to identify risk factors for death.

    We performed a single-centre, observational study from 1 January 2019 to 31 December 2024, including patients with OHS.

    Among 167 included patients, 44 (26.4%) died as of 31 December 2024. 5-year mortality was 12.6%.In multivariable Cox regression, independent predictors of mortality were: OHS diagnosed during acute respiratory failure (HR 6.60, 95% CI 1.50 to 29.10), irregular follow-up (HR 5, 95% CI 1.82 to 14.29), left heart disease (HR 3.63, 95% CI 1.51 to 8.70), lower haematocrit (HR 1.12 per percentage point, 95% CI 1.03 to 1.22) and older age at diagnosis (HR 1.04 per year, 95% CI 1.01 to 1.08).

    Mortality among patients with OHS in Martinique remains high. Strategies to improve early diagnosis, cardiovascular risk management and long-term follow-up are essential to improving outcomes in this high-risk population.
    Chronic respiratory disease
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  • Performance indicators for evaluating and optimising hospital services during COVID-19: a scoping review.
    4 days ago
    To identify which logistical and clinical healthcare key performance indicators (KPIs) were applied in hospitals during the COVID-19 pandemic and how frequently they were used when evaluating and optimising hospital care services.

    Scoping review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) framework.

    The search was performed in PubMed, CINAHL, EMBASE, Scopus and Web of Science and included articles published from the beginning of the COVID-19 pandemic, that is, 1 January 2020, until 11 November 2024, the date of the final search. The search strategy combined terms related to (1) COVID-19/pandemic, (2) performance and (3) hospital care.

    Eligible studies were peer-reviewed, English-language publications that reported measurable performance indicators evaluating or optimising hospital care services during the COVID-19 pandemic. Studies had to explicitly define or evaluate KPIs and focus on inpatient hospital settings (≥1 overnight stay) in countries within the European Union, the European Economic Area, the Schengen area or the UK. Multicountry or global studies were included when they contained relevant European data or when the geographical context was not determinant (eg, modelling studies). Exclusion criteria included non-peer-reviewed publications, conference abstracts, organisational reports, literature reviews, studies without original results, studies without accessible full text and non-English publications.

    Titles, abstracts and full texts were screened independently by three reviewers. Disagreements were resolved through discussion and consultation with two additional reviewers. Relevant study characteristics and KPI-related information were extracted using a predefined data extraction form. KPIs were categorised inductively into thematic categories. Structured data were analysed at both the study and KPI-category level. Data without a predefined structure, such as KPI definitions and key findings, were analysed manually at the KPI-category level.

    Across 94 included studies, 459 distinct KPIs were extracted. Given substantial heterogeneity, KPIs were grouped inductively into six main categories: (1) clinical outcomes, (2) resources and capacity, (3) care delivery volumes, (4) care delivery performance, (5) access time and sojourn time and (6) other indicators. KPIs were reported in diverse formats, including volumes, percentages, scores, scales, characteristics and binary outcomes. Identical KPIs were sometimes defined differently across studies, while similar measures were reported under different terminology. The most common reason for KPI use was for the comparison between pre-COVID-19 and COVID-19 periods, followed by supporting optimisation and exploring quality of care during the pandemic. Most studies emphasised either clinical or logistical indicators, with limited integration of both perspectives within a single performance assessment. The majority of KPIs were not pandemic-specific but reflected indicators already used in routine hospital performance monitoring.

    Hospital performance during COVID-19 was evaluated using a wide range of heterogeneous KPIs, with substantial variation in definitions and reporting practices. Greater transparency and standardisation in KPI definitions may improve comparability, reproducibility and preparedness for future health crises. Integrating clinical and logistical performance perspectives may provide a broader view of hospital performance and support decision-making during pandemics.
    Chronic respiratory disease
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  • SADIE: a longitudinal Survey on Anxiety, Depression, Internalising and Externalising symptoms in Italian university students - a study protocol.
    4 days ago
    University students experience escalating academic, social and financial stress, resulting in high prevalence of anxiety (18%-40%), depression (12-35%) and burnout (20-30%). The COVID-19 pandemic intensified these issues, but most studies report symptom remission post-lockdown, highlighting the need for long-term prospective data on symptom trajectories and risk factors. The Survey on Anxiety, Depression, Internalising and Externalising symptoms (SADIE) study aims to (1) estimate the prevalence and incidence of anxiety, depression, burnout and suicidal ideation in Italian university students over 36 months and (2) identify modifiable psychological and behavioural predictors-such as multidimensional perfectionism, academic stress and substance use-associated with adverse symptom trajectories.

    We will recruit 5000 undergraduates and postgraduates (aged ≥18 years, fluent in Italian or English) from 14 Italian universities. Participants will complete online assessments via REDCap at baseline, 6-month, 18-month and 36-month follow-ups. Measures include demographic survey, Maslach Burnout Inventory-2, Beck Depression Inventory-II, Generalized Anxiety Disorder-7, WHO-5 Well-Being Index, Alcohol Use Disorders Identification Test-3, Cigarette Dependence Scale-5, Columbia Suicide Severity Rating Scale and Hewitt and Flett Multidimensional Perfectionism Scale. Mixed-effects models (R/lme4) and growth-mixture models will be used to evaluate symptom trajectories, while logistic regression will identify predictors of adverse outcomes. Sensitivity analyses will address potential self-selection and attrition bias.

    The study has received approval from the Ethics Committee of the University of Padova (Protocol No. 235-d). Participants will provide electronic informed consent and may withdraw at any time. Risk management includes automated alerts and links to local mental health services for high-risk responses. Study findings will be disseminated through peer-reviewed publications, conference presentations and summary reports to participating institutions; deidentified data may be made available on reasonable request in line with institutional and data protection regulations.
    Chronic respiratory disease
    Mental Health
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  • Predictors of response to mepolizumab for severe asthma: a REDES study post hoc analysis.
    4 days ago
    To identify predictors of treatment response to help target mepolizumab to patients with severe asthma with type 2 inflammation (SA-T2) who are most likely to respond to therapy.

    The REal-worlD Effectiveness and Safety of mepolizumab (REDES), a multicentre, observational cohort study, investigated the effectiveness and safety of mepolizumab in Spanish patients with SA-T2.

    We conducted a post hoc analysis of data from REDES to examine relationships between patient characteristics and response to mepolizumab to identify predictive markers of response. Outcomes included annualised clinically significant exacerbations (primary), lung function (forced expiratory volume in 1 s), maintenance oral corticosteroid (OCS) dose and Asthma Control Test (ACT) score. Outcomes after 12 months' treatment with mepolizumab were assessed and stratified by demographic and clinical characteristics. Analyses were descriptive; changes from baseline were summarised as mean (SD) and prespecified two-tailed unpaired t-tests were applied for comparisons (p<0.05).

    These were stratified by various demographic and clinical characteristics collected during the study.

    In total, 318 patients with SA-T2 were included in the analysis. Mepolizumab was effective in patients with a diverse range of demographic and clinical characteristics. Baseline blood eosinophil count ≥150 or ≥300 cells/µL or fraction of exhaled nitric oxide (FeNO) ≥25 or ≥50 ppb resulted in a 77%-88% reduction in exacerbations compared with 51%-55% in patients with lower baseline levels of these biomarkers (descriptive). Baseline factors of sex, body mass index, smoking status, atopic sensitisation and forced expiratory volume in 1 s had no appreciable effects on exacerbations, maintenance OCS use, lung function or asthma symptoms.

    This post hoc analysis indicates mepolizumab is likely to provide clinical benefit in patients with SA-T2 across a broad range of patient characteristics. Patients with baseline blood eosinophils of ≥150 cells/µL and/or FeNO ≥25 ppb are likely to derive more benefit.

    213172.
    Chronic respiratory disease
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  • Crohn's disease unmasks pulmonary sarcoidosis on biologic screening: dual granulomatous pathology responsive to infliximab.
    4 days ago
    A man in his 30s with longstanding ileal Crohn's disease was found to have pulmonary sarcoidosis during routine pre-biologic evaluation. Although he had no respiratory symptoms, lung function testing showed mildly reduced diffusion capacity. Radiological imaging demonstrated diffuse pulmonary nodules and mediastinal lymphadenopathy, and transbronchial biopsies confirmed non-necrotising granulomas consistent with sarcoidosis. In the setting of postoperative endoscopic Crohn's recurrence and pulmonary sarcoidosis with mildly reduced diffusion capacity, infliximab was selected to provide dual disease control. Crohn's disease improved endoscopically and histologically, while follow-up CT showed radiological improvement of the pulmonary sarcoidosis. This case highlights the diagnostic complexity of overlapping granulomatous diseases and the potential therapeutic advantage of tumour necrosis factor-alpha inhibition when treatment of both conditions is being considered.
    Chronic respiratory disease
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  • Surveillance for severe influenza, COVID-19, and RSV in patients admitted to sentinel Australian hospitals in 2025: the Influenza Complications Alert Network (FluCAN) and the Paediatric Active Enhanced Disease Surveillance (PAEDS) system.
    4 days ago
    Influenza, coronavirus disease 2019 (COVID-19) and respiratory syncytial virus (RSV) are common acute respiratory infections and are a cause of significant morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza, COVID-19 and RSV in 2025 in an Australian sentinel surveillance system.

    The Influenza Complications Alert Network (FluCAN) and the Paediatric Active Enhanced Disease Surveillance (PAEDS) are collaborative sentinel hospital-based surveillance programs that operate at 23 sites across all jurisdictions in Australia. Influenza, COVID-19 and RSV patients were defined as those hospitalised due to an acute respiratory infection at the sentinel hospitals with virus confirmation by nucleic acid detection.

    In 2025, there were 8,749 hospitalisations of patients with influenza; 3,501 with COVID-19; and 5,105 with RSV reported at the 23 sentinel hospitals. Of patients hospitalised with influenza, 4,397 (50.3%) were children (< 16 years of age); 697 (8.0%) were Aboriginal and/or Torres Strait Islander people; and 5,020 (57.4%) had chronic comorbidities. The mean length of hospital stay for patients with influenza was 4.4 days (median: 2 days). Influenza hospital admissions peaked nationally in epidemiological week 28. Influenza vaccine effectiveness against hospitalisation with any influenza type/subtype was estimated at 43% (95% confidence interval [95% CI]: 39-48%) and was highest for influenza B (75% [95% CI: 69-80%]), and lowest for influenza A H3N2 including subclade K (30.5% [95% CI: 15.0-43.2%]). Of patients hospitalised with COVID-19, 1,057 (30.2%) were children (< 16 years of age); 230 (6.6%) were Aboriginal and/or Torres Strait Islander people; and 2,544 (72.7%) had chronic comorbidities. The mean length of hospital stay for patients with COVID-19 was 7 days (median: 3 days). COVID-19 hospital admissions peaked nationally in week 26. In adults ≥ 75 years of age, the relative risk of hospitalisation was 40% (95% CI: 25-52%) lower in those who had received a COVID-19 vaccine within 180 days, compared to those vaccinated > 1 year prior to admission. Of patients hospitalised with RSV, 1,551 (30.4%) were infants (< 1 year of age) and 3,723 (72.9%) were young children (< 5 years of age); 348 (6.8%) were Aboriginal and/or Torres Strait Islander people; and 2,110 (41.3%) had chronic comorbidities. The mean length of hospital stay for patients with RSV was 3.5 days (median: 2 days). There was a peak in activity in week 28.

    Since 2022, influenza, RSV and COVID-19 have co-circulated. In 2025, disease severity-as indicated by average length of stay and proportions admitted to intensive care-was similar in patients hospitalised with any of the three pathogens. Assessment of vaccine effectiveness demonstrated protection against influenza hospitalisation and short-term protection against hospitalisation with COVID-19 in older people.
    Chronic respiratory disease
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  • Enhancing influenza surveillance in Australia using Google search data combined with machine learning.
    4 days ago
    To effectively respond to acute respiratory infections such as influenza, timely information about the spread of disease is required. Surveillance methods that train machine learning models on Google Trends data have been developed to forecast outbreaks. Our aim was to examine the feasibility of forecasting influenza rates for states and territories in Australia using Google Trends data.

    Weekly search volume data across 2018 and 2019 from Google Trends, for each state and territory in Australia excepting the Australian Capital Territory, were compared to weekly influenza notifications from the National Notifiable Disease Surveillance System (NNDSS). Four supervised machine learning regression models were developed: elastic net; support vector regression; random forest; and feedforward neural network. Models were fitted independently to data from each state and territory, considering nowcast (current week) and forecast (one and two weeks ahead) predictions.

    The results show that Google search volumes are correlated with reported influenza rates over time. Random forest and elastic net models generally showed better predictive performance compared to other models. Each modelled state and territory, except the Northern Territory and Tasmania, showed at least two search queries with moderate to strong Pearson correlation with the influenza notifications. The forecast accuracy (measured by the Pearson correlation coefficient) for the best-performing model varied by state or territory (from -0.353 to 0.977) and accuracy was lower for forecasts for one week and two weeks ahead.

    Combinations of Google search data and machine learning showed predictive utility for forecasting weekly influenza rates in Australian jurisdictions, with lower accuracy in jurisdictions with smaller populations. Future work should investigate specific keywords by location exploring disease prediction at a more geographically specific level, with considerations for smaller populations and robustness over time.
    Chronic respiratory disease
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