High-dose (HD) influenza vaccines have demonstrated robust effectiveness in preventing severe influenza-related outcomes, including pneumonia, cardiorespiratory complications, and mortality, with evidence from randomized clinical trials, meta-analyses, and real-world studies consistently showing superiority over standard-dose (SD) vaccines and supporting international recommendations for adults aged ≥60 years. This is increasingly relevant in the context of global aging and immunosenescence, which weakens vaccine-induced immune responses and heightens biological frailty, functional decline, and the risk of severe complications in older adults, especially those with comorbidities. The objective of this work is to describe the introduction, uptake, and current use of HD influenza vaccines in Spain and to summarize the evidence supporting their broader adoption in adults ≥60 years of age. Methods include a narrative synthesis of clinical evidence and an analysis of vaccination strategies implemented across Spanish autonomous communities since the introduction of HD vaccines during the COVID-19 pandemic. Available evidence supports extending HD vaccine use as a population-based strategy to enhance protection and promote equitable access. The results show that the incorporation of HD influenza vaccines marked a significant shift in national vaccination strategies, with heterogeneous uptake across regions: while some prioritized institutionalized or dependent populations, others implemented mixed approaches that also included community-dwelling adults aged ≥60 years. In conclusion, a clear trend toward wider adoption is emerging, with an increasing number of autonomous communities incorporating HD vaccines into their programs and progressively lowering the recommended age threshold, in alignment with international guidance and the biological rationale for strengthened protection in older adults.

The underlying pathogenesis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is closely related to airway microbiota dysregulation. Currently, there is a lack of systematic elaboration based on deep metagenomic sequencing regarding the species-level and functional characteristics of the microbiota during AECOPD, as well as its correlation with clinical phenotypes of the host. This study aims to systematically analyze the taxonomic composition and functional profile changes of the microbiota in induced sputum samples from COPD patients during the stable and acute exacerbation periods using metagenomic next-generation sequencing and to explore their correlations with clinical indicators through metagenomic methods.

A total of 66 patients with COPD were recruited from the Department of Respiratory and Critical Care Medicine at Jiading District Central Hospital in Shanghai, China. Of these, 49 induced sputum samples were obtained from 47 patients (17 in the stable group; 30 in the acute exacerbation group) after the quality control with DNA extraction and deep metagenomic sequencing. The species annotation and functional analysis were conducted using bioinformatics procedures, and microbial α-diversity analysis, LEfSe analysis was performed to identify differentially expressed markers. Spearman correlation analysis was used to evaluate the correlation between microbial/functional characteristics and a series of clinical indicators.

The α-diversity of the sputum microbiota in AECOPD patients was significantly lower at the species level compared to the stable stage (p < 0.01), and the community structure also underwent significant changes. Functional annotation and comparative analysis further identified 9 KEGG pathways (ko00970, ko04112, ko03420, ko03440, ko03060/ko03070, ko03410, ko04930, and ko00680) and 1 eggNOG functional category (M: Cell wall/membrane/envelope biogenesis) that differed significantly between the two groups. Among them, pathways such as methane metabolism were downregulated in the exacerbation period.

This study revealed significant dysregulation of the airway microbiome in AECOPD patients at species-level diversity, community structure, and functional metabolism, providing a molecular basis for the discovery of functional biomarkers and therapeutic targets in the microbiome.

In view of the established role of endothelial dysfunction in the pathophysiology of chronic obstructive pulmonary disease (COPD), the Endothelial Activation and Stress Index (EASIX), a validated biomarker of endothelial injury, warrants investigation as a potential prognostic tool. We therefore investigated its association with outcomes in critically ill COPD patients.

This retrospective cohort study analyzed data from critically ill patients with COPD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure was log2(EASIX) (continuous or tertiles). The outcomes were 28‑, 60‑, and 90‑day all‑cause mortality. Cox regression was primarily used to assess the association, and multiple additional approaches were employed to verify its robustness.

A total of 1534 patients were included. Kaplan‑Meier survival curves showed significantly lower survival probabilities in higher EASIX tertiles (log‑rank p < 0.01 for all comparisons). Multivariable Cox regression confirmed that higher log2(EASIX) was independently associated with increased 28‑, 60‑, and 90‑day all‑cause mortality, with adjusted hazard ratios (HRs) of 1.87 (95% CI: 1.31-2.58), 1.83 (95% CI: 1.33-2.52), and 1.84 (95% CI: 1.36-2.50), respectively (all p < 0.01). Restricted cubic spline analysis indicated a linear relationship, and the association was robust across clinical subgroups. Sensitivity analyses in the fully imputed cohort confirmed linearity at 28 and 60 days but revealed a U‑shaped relationship at 90 days, with a nadir at log2(EASIX) = 0.56 (original EASIX = 1.47) and a HR of 0.74 (95% CI: 0.58-0.96). The E‑value of 2.96 (lower confidence bound 1.88) indicates robustness to unmeasured confounding.

Higher EASIX is independently associated with 28-day and 60-day mortality in critically ill COPD patients, whereas the 90-day relationship appears more complex. These findings suggest that EASIX may aid early risk assessment, pending external validation.

To evaluate the efficacy and safety of dupilumab combined with triple inhaled therapy in patients with chronic obstructive pulmonary disease (COPD) with type 2 inflammation in a real-world setting.

This retrospective cohort study included patients with COPD and a type 2 inflammatory phenotype treated at the First Affiliated Hospital of Soochow University between October 2024 and December 2025. Propensity score matching (1:1) was performed to generate a study group receiving dupilumab plus triple therapy (ICS/LABA/LAMA) (n = 34) and a control group receiving triple therapy alone (n = 34). Pulmonary function, symptom scores, inflammatory biomarkers, acute exacerbations, and adverse events were assessed over 24 weeks.

After 24 weeks, improvements in pulmonary function, symptom burden, and airway inflammation were observed in patients receiving dupilumab combined with triple therapy. In the dupilumab group, FEV₁ increased by 0.20 L, CAT score decreased by 3.70 points, and FeNO levels decreased by 8 ppb. Compared with the control group, greater associated improvements were observed in FEV₁ (adjusted between-group difference: 0.12 L) and FEV₁% predicted, along with greater reductions in CAT score, mMRC score, and FeNO levels (all P < 0.05). The annualized exacerbation rate was lower in the study group than in the control group (0.49 vs. 1.21 events per person-year), with regression analyses showing results approaching statistical significance (P = 0.058). Adverse events were mainly mild injection-site reactions and did not affect treatment continuation.

Dupilumab combined with triple inhaled therapy was associated with improvements in lung function, symptom burden, and airway inflammation in COPD patients with type 2 inflammation, with a favorable safety profile. A potential reduction in exacerbation risk was also observed, although further prospective studies are needed for confirmation.

COVID-19 has posed significant challenges worldwide, with pregnant individuals identified as being at increased risk for severe illness and poor outcomes compared to the general population. This study aimed to compare the course of critical illness due to COVID-19 of pregnant patients to nonpregnant reproductive-age women and describe their perinatal outcomes. A retrospective cohort study was conducted including women ages 14-49 years admitted to the intensive care unit (ICU) with COVID-19-related illness from 3/2020 to 2/2022 at Vanderbilt University Medical Center in Nashville, Tennessee. Demographic, clinical characteristics, and outcomes were compared between pregnant/postpartum and nonpregnant patients. Neonatal outcomes were also analyzed. Among 159 women, 35 (22%) were pregnant or postpartum. Pregnant patients had a lower body mass index, were more likely to be publicly insured, and were less likely to have underlying comorbidities. The groups had similar proportions of mechanical ventilation, venous thromboembolism, and death. However, pregnant patients were more likely to require extracorporeal membrane oxygenation (ECMO). The proportion of individuals who were vaccinated against COVID-19 was low in both groups. Of 19 neonates born, the mean gestational age was 32.9 weeks, with 94.7% delivered via cesarean and 78.9% requiring NICU admission. Five intrauterine fetal demises and one neonatal death occurred. Though pregnant patients admitted to the ICU with COVID-19 had fewer comorbidities compared to nonpregnant women, nearly one-fifth of them required ECMO. Pregnant patients with COVID-19 ICU admission face high risks of ECMO, preterm delivery, cesarean, and fetal loss. Improving vaccination uptake is critical, especially in this population.

Objective: To investigate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure and vascular endothelial function in patients with hypertension and moderate-to-severe obstructive sleep apnea (OSA). Methods: This was a retrospective study. Patients diagnosed with hypertension and moderate-to-severe OSA in the Department of Hypertension, Tianjin Kanghui Hospital, from October 2023 to December 2024 were enrolled. Patients were divided into the observation group (received standard CPAP therapy ≥4 hours per night and ≥5 nights per week) and the control group (did not receive CPAP therapy). Both groups received standard antihypertensive medication and were observed continuously for 24 weeks. Vascular endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery, and blood pressure fluctuations were evaluated by ambulatory blood pressure monitoring. Spearman rank correlation analysis was used to evaluate the correlation between changes in endothelial function and changes in blood pressure parameters. Antihypertensive medication load was assessed using the defined daily dose of antihypertensive drugs. Results: A total of 109 patients with hypertension and moderate-to-severe OSA were enrolled, with an age of (47.13±11.21) years, including 15 females (14%). There were 54 patients in the observation group and 55 in the control group. After 24 weeks of treatment, FMD was higher in the observation group than in the control group ((7.15±1.15)% vs. (4.08±1.46)%, P0.001). Ambulatory blood pressure monitoring showed that the mean 24-hour systolic blood pressure ((120.96±5.27) mmHg vs. (124.71±3.15) mmHg) and mean 24-hour diastolic blood pressure ((77.36±6.99) mmHg vs. (81.60±3.67) mmHg) were lower in the observation group than in the control group (both P0.05). Specifically, the mean daytime systolic blood pressure ((123.86±5.83) mmHg vs. (126.73±4.65) mmHg), mean daytime diastolic blood pressure ((80.12±7.16) mmHg vs. (82.75±4.61) mmHg), mean nighttime systolic blood pressure ((116.40±5.37) mmHg vs. (123.12±5.99) mmHg), and mean nighttime diastolic blood pressure ((72.57±7.54) mmHg vs. (80.29±5.67) mmHg) were all lower in the observation group than control group (all P0.05). The nighttime systolic blood pressure dipping ratio ((5.88±2.73)% vs. (3.13±4.45)%) and nighttime diastolic blood pressure dipping ratio ((9.37±5.65)% vs. (2.89±5.92)%) were higher in the observation group than the control group (both P0.05). In addition, the defined daily dose of antihypertensive drugs was lower in the observation group than in the control group ((1.60±0.86) vs. (2.26±0.87), P0.001]. Spearman rank correlation analysis showed that changes in FMD were negatively correlated with the reduction in mean nighttime diastolic blood pressure only in the observation group (r=-0.441, P=0.001). Conclusion: CPAP therapy is associated with improved vascular endothelial function, reduced blood pressure and reversal of non-dipper blood pressure rhythm in hypertensive patients with moderate to severe OSA.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is the most common autoinflammatory syndrome of childhood. Although immune dysregulation is central to its pathogenesis, the broader burden of allergic and autoimmune comorbidities in PFAPA remains incompletely characterized. We aimed to evaluate the prevalence of allergic and autoimmune diseases in children with PFAPA.

We conducted a nationwide matched case-control study using electronic health records from Leumit Health Services in Israel between 2000 and 2024. Children with PFAPA were identified using a dedicated ICD-9 code and matched 1:20 with controls by age, sex, socioeconomic status, ethnicity, and year of first record. Allergic and autoimmune diagnoses were identified using predefined ICD-9 codes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with false discovery rate correction for multiple testing.

The cohort included 1641 PFAPA patients and 32,820 matched controls with a mean follow-up of 8.6 years. PFAPA patients had increased prevalence of asthma (49.6% vs. 37.5%; OR 1.64), allergic rhinitis (15.7% vs. 9.8%; OR 1.71), atopic dermatitis (23.0% vs. 19.9%; OR 1.21), urticaria (18.8% vs. 15.0%; OR 1.32), drug allergy (1.22% vs. 0.57%; OR 2.15), and anaphylaxis (0.55% vs. 0.20%; OR 2.78). In contrast, autoimmune diseases were uncommon and showed no consistent enrichment. Similar associations were observed for diagnoses recorded before PFAPA diagnosis.

PFAPA is associated with a broad atopic comorbidity profile but not with classical autoimmune disease. These findings suggest that PFAPA may represent a distinct immune phenotype in which episodic autoinflammation coexists with atopic susceptibility.

This study focuses on how a South African Indigenous community sustained wellbeing during and after the COVID-19 pandemic, informed by their spiritual belief systems. The study also documents the home remedies and strategies the communities utilised during this health crisis.

Applying a postcolonial lens within a qualitative approach, data were gathered from 25 participants across four communities through 10 interviews and two focus groups. Thematic data analysis was verified through three community collaborative workshops with study participants.

Study outcomes show that, inclusive of other issues of health and wellbeing, the isolation of self from other human contact, and the lack of consultative processes for spiritual health management between the community and government during the pandemic, were major challenges.

COVID-19 guidelines were relevant, but these guidelines need to be implemented through collaborative processes to inform future health crises within Indigenous communities.

Government guidelines, although deemed necessary, should be implemented within a more inclusive approach that acknowledges the knowledge on ground, and the daily lived experiences of Indigenous communities.

This paper presents research on a Predictive and Uncertainty Assessment Framework (PUAF), providing a comparative analysis of two prominent methods, Monte Carlo (MC) Dropout and Bootstrap-based models, used in uncertainty estimation techniques of Neural Network predictions of human activity recognition using accelerometer data. Unlike traditional studies that optimize classification accuracy, this work emphasizes uncertainty quantification to enhance model reliability, particularly for critical health-related activities. Among the five activity classes of Sit, Sleep, Walk, Cough and Fall, this work concentrates on the Cough and Fall cases. The study exploits acceleration data from a wearable device positioned on the user's chest, with features derived from three-axis motion measurements. Synthetic datasets are generated by systematically introducing noise variations, added to the original dataset across all axes, to assess robustness under real-world conditions. Each uncertainty estimation method estimates the probabilities for the five different classes along with the corresponding 95% confidence intervals to quantify the prediction uncertainty. A detailed evaluation is conducted by analyzing the average width of these confidence intervals across different noise levels, identifying the most reliable feature and model combination. Both the MC Dropout and Bootstrap enhance model robustness and uncertainty awareness under noisy sensor conditions. The MC Dropout provides sharper and more sensitive uncertainty estimates, while the Bootstrap yields more stable and better-calibrated predictions. The evaluation using the proposed PUAF demonstrates that each method offers distinct advantages, highlighting the importance of uncertainty quantification for reliable wearable-based HAR systems.

Vitamin D is believed to exert an immunomodulatory effect in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and may influence the intensity of inflammatory processes. Therefore, this study aimed to assess serum vitamin D levels in relation to selected cytokines in patients with CRSwNP and without nasal polyps (CRSsNP). This prospective study included patients with clinically and radiologically confirmed diseases. In total, 39 patients were included in three phenotypic groups: CRSwNP (n = 17), CRSsNP (n = 10), and controls (n = 12). Serum concentrations of vitamin D (25(OH)D3), interleukins 4, 5, 17A, interferon-γ (IFN-γ), and immunoglobulin E were assessed preoperatively. The extent of subjective and objective mucosal disease was evaluated using endoscopic and radiological staging, based on the Lund-Kennedy and Lund-Mackay scoring systems in accordance with the Sino-Nasal Outcome Test-22 (SNOT-22), respectively. Patients with CRSwNP demonstrated higher serum IL-4 and IL-5 concentrations, consistent with a Th2-skewed inflammatory profile, whereas patients with CRSsNP showed higher IL-17A and IFN-γ levels, suggesting a mixed Th17/Th1 inflammatory pattern. IL-5 was positively associated with radiological disease severity. Serum vitamin D levels tended to be inversely associated with IL-5 concentration and disease severity; however, these associations did not reach statistical significance.: The findings of this study support differences in inflammatory profiles between CRSwNP and CRSsNP and confirm an association between IL-5 and radiological disease severity. Although lower vitamin D levels showed a trend toward greater inflammatory activity and disease severity, no statistically significant associations were demonstrated in this cohort. Further studies with larger populations are warranted to clarify the role of vitamin D in CRS endotypes.