Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare necrotizing vasculitis involving upper- and lower-airways. Despite biologics, sinonasal disease often persists. Evidence on ENT trajectories under anti-IL5 treatment and role of endoscopic sinus surgery (ESS) remains limited and is often described without standardized assessment tools. This study provides a systematic, multidimensional evaluation of sinonasal outcomes under biologic therapy and analyzes the role of ESS in a real-life cohort.

We retrospectively analyzed 52 EGPA patients with a 24-month follow-up on mepolizumab. Sinonasal disease was assessed by Nasal Polyp Score (NPS), Lund-Kennedy Score (LKS), Lund-Mackay score (LMK), and SNOT-22, while systemic activity was assessed by Birmingham Vasculitis Activity Score (BVAS). Patients were stratified by mepolizumab regimen (100 mg, 300 mg, and step-down). Predictors of adjunctive ESS were explored through multivariate logistic regression.

Systemic remission occurred in >90% of patients, with marked eosinophil suppression (median 700 → 59.5 cells/µL) and BVAS = 0. Conversely, NPS and LKS remained stable [IQR]: (NPS 4 [3-5] → 4 [2-5]; LKS 6 [4-8] → 5 [2-7.75]. Polyps persisted in 64% and mucosal edema/discharge in 92% of population. Continuous 100 mg therapy showed the greatest endoscopic improvement. Higher baseline sinonasal burden, more extensive surgical history, and mepolizumab dose variation were associated with adjunctive ESS (28.8%), whereas BVAS and eosinophils showed no correlation with ENT severity.

Sinonasal disease may persist despite systemic remission, suggesting a partially independent inflammatory niche. Comprehensive assessment should combine systemic markers with dedicated ENT evaluation, while management may require integrated biologic-surgical strategies in chronic structural disease.

Acute respiratory distress syndrome (ARDS) is associated with profound pulmonary surfactant dysfunction, yet clinical trials of exogenous surfactant have not demonstrated consistent outcome benefits in adults. This review reassesses these failures in light of current understanding of ARDS heterogeneity, surfactant biology and intrapulmonary drug delivery.

Surfactant dysfunction in ARDS reflects not only quantitative depletion but also inhibition by plasma proteins, altered lipid and protein composition, impaired synthesis and recycling, epithelial injury and heterogeneous alveolar flooding. Previous trials frequently enrolled biologically unselected populations and used variable formulations, doses and delivery strategies. Available evidence provides a rationale for a phenotype-guided approach integrating patient selection, assessment of surfactant dysfunction, formulations capable of maintaining activity under inhibitory conditions and optimized alveolar delivery. Next-generation synthetic surfactants containing surfactant protein B and C analogues, together with surfactant-based delivery of anti-inflammatory or other biologically active compounds, may address limitations of earlier replacement strategies. Future studies should move beyond testing surfactant in unselected ARDS. Clinical translation will require biologically enriched populations, mechanistically appropriate formulations, early treatment and verified delivery to recruitable lung regions.

Sepsis-induced acute lung injury (ALI) is closely associated with the balance of M1/M2 macrophage polarization and excessive inflammation. Recently studies have revealed that TMEM16F, a calcium-activated phospholipid scramblase, participates in modulating inflammatory response and oxidative stress. However, the effect of TMEM16F on regulation of M1/M2 polarization during sepsis-induced ALI and its underlying mechanisms remain unclear.

In the present study, we utilized septic patients, lipopolysaccharide (LPS)-induced ALI mouse models, and LPS-treated mouse alveolar macrophages (AMs) as well as human THP-1-derived macrophages to investigate the potential functions and molecular mechanisms of TMEM16F in sepsis-induced ALI.

Our clinical analysis showed that TMEM16F mRNA levels in peripheral blood mononuclear cells (PBMCs) were positively correlated with inflammation and disease severity in septic patients. Additionally, TMEM16F was highly expressed in LPS-treated THP-1 macrophages and in vitro sepsis-induced ALI models. TMEM16F knockout significantly promoted M2 macrophage polarization, alleviated systemic inflammation, lung injury, oxidative stress and microthrombosis, and improved survival in septic mice. Mechanistically, TMEM16F could interact with SOCS3, suppressing downstream STAT3 signaling pathway and promoting NLRP3 inflammasome activation, resulting in increased M1 polarization and inflammatory response. Moreover, we identified platycodin D (PLD), a saponin found from Platycodon grandiflorum, could be an effective inhibitor of TMEM16F, and ameliorate sepsis-induced ALI by reprogramming macrophages towards an anti-inflammatory phenotype via inhibiting TMEM16F-mediated SOCS3/STAT3/NLRP3 pathway.

Collectively, these findings indicated that TMEM16F plays a crucial role in regulating macrophage phenotypic switching, and highlighted targeting TMEM16F is a therapeutic strategy for attenuating sepsis-associated ALI through immune homeostasis restoration.

Individuals with immunosuppression are at an increased risk of severe respiratory syncytial virus (RSV) disease. We aimed to evaluate the effectiveness of a bivalent RSV prefusion F protein-based vaccine (RSVpreF) in older adults (≥60 years) according to immunosuppression status.

This study was a prespecified subgroup analysis of a pragmatic, open-label, nationwide randomised clinical trial conducted in Denmark during November-December, 2024. Older adults were randomised 1:1 to a single dose of RSVpreF or no vaccine. Immunosuppression was defined as at least one hospital encounter with an immunosuppressive condition or treatment. Baseline characteristics and outcomes were ascertained from nationwide registries. The primary outcome was hospitalisation for RSV-related respiratory tract disease, defined as respiratory hospitalisation with an RSV diagnosis code or a positive RSV test. Follow-up began 14 days after the scheduled study visit and continued until May 31, 2025.

Among the 131 276 participants (65 642 RSVpreF; 65 634 no vaccine), 5199 (4·0%) were immunosuppressed. In total, 21 participants were hospitalised with RSV-related respiratory tract disease, seven with immunosuppression, and 14 without immunosuppression. In the no-vaccine group, the incidence of RSV-related respiratory tract disease hospitalisation was more than nine-fold higher in participants with immunosuppression than in participants without (4·68 vs 0·50 events per 1000 person-years). As previously shown, RSVpreF significantly reduced RSV-related respiratory tract disease hospitalisations in the overall population (vaccine effectiveness 83·3% [95% CI 42·9 to 96·9]). No significant effect modification by immunosuppression status was observed (vaccine effectiveness 60·5% [95% CI -141·4 to 96·2] among those with immunosuppression and 92·3% [48·7 to 99·8] among those without immunosuppression; p for interaction=0·22). The point estimate was numerically lower among participants with immunosuppression, with a wide confidence interval crossing the null, but there was no statistical evidence of heterogeneity between subgroups. The estimated absolute rate reduction was 2·83 events per 1000 person-years (95% CI -2·00 to 7·66) among the participants with immunosuppression and 0·46 events per 1000 person-years (0·18 to 0·74) among those without immunosuppression.

In adults aged 60 years or older, RSVpreF vaccination reduced hospitalisations for RSV-related respiratory tract disease with no statistical evidence of effect modification by immunosuppression status; however, the study was not powered to exclude subgroup differences. Given the higher baseline risk of RSV-related hospitalisation observed among the individuals with immunosuppression, prioritising RSV vaccination in this group with high risk of severe RSV disease could have clinical benefits. The results of this trial could help to inform clinical guidance and vaccination policy, pending confirmation in larger studies.

The Danish respiratory syncytial virus trial was supported by Pfizer.

The excessive activation of sympathetic nerve is closely related to cardiovascular diseases (CVDs). In this study, we developed a novel MIL-100(Fe)@Ag surface-enhanced Raman scattering (SERS) substrate for the simultaneous and effective detection of plasma norepinephrine (NE) and adenosine-two pivotal sympathetic hormones. The microscopic morphology and crystal structure of the substrate were characterized using techniques such as transmission electron microscope (TEM) and X-ray diffraction (XRD). Mechanistically, the HOMO-LUMO energy levels of the detection molecules were calculated using Gaussian. The substrate realized a dual SERS enhancement mechanism through the synergistic effect of localized surface plasmon resonance and interfacial charge transfer. Consequently, the MIL-100(Fe)@Ag platform exhibited high-sensitivity quantitative detection capabilities for NE and adenosine: the detection limit for NE is 0.596 nmol/L; the detection limit for adenosine is 0.24 nmol/L. Crucially, when applied to patients with pheochromocytoma-a neuroendocrine tumor characterized by plasma catecholamine surges, this method achieved robust and stable detection of plasma NE. It offered comparable diagnostic accuracy to conventional mass spectrometry while significantly reducing analysis complexity. Therefore, this innovative strategy may hold great promise for the long-term, decentralized monitoring of sympathetic nerve activity in populations at risk for CVDs or related clinical disorders.

To determine the prevalence of chronic kidney disease (CKD) and associated factors among adults with hypertension attending a tertiary cardiac clinic in Tanzania.

Hospital-based cross-sectional study.

Tertiary cardiac outpatient clinic in Dar es Salaam, Tanzania.

A total of 162 adults aged ≥18 years with documented hypertension attending follow-up care from 15 June to 30 July 2024 were recruited using simple random sampling.

The primary outcome was study-defined CKD, classified from available records as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m² and/or urine dipstick proteinuria ≥1+. Urine albumin-to-creatinine ratio (UACR) and confirmation of persistence for ≥3 months were not available for all participants. Factors associated with CKD were assessed using crude and multivariable logistic regression.

Among 162 hypertensive patients, 34 met the study-defined CKD criteria, giving a prevalence of 21.0% (95% CI 15.4% to 27.9%). Median serum creatinine was 94 µmol/L (IQR 77-122; range 48-286) and median eGFR was 77 mL/min/1.73 m² (IQR 62-92; range 19-118); 29 (17.9%) participants had eGFR <60 mL/min/1.73 m². Diabetes was independently associated with CKD (adjusted OR 3.257, 95% CI 1.167 to 9.091, p=0.024). Uncontrolled hypertension was not statistically associated with CKD after adjustment (adjusted OR 1.330, 95% CI 0.546 to 3.236, p=0.531); age, sex and education level were also not significant.

Study-defined CKD was identified in about one-fifth of this tertiary-clinic hypertensive sample, and diabetes was the only independent factor identified. The estimate should be interpreted cautiously because the study was single-centre and full Kidney Disease: Improving Global Outcomes confirmation using chronicity and UACR was not available for all participants. Multicentre studies using repeated eGFR and quantitative albuminuria assessment are needed.

Cerebral small vessel disease (CSVD) is a major cause of ischemic stroke and cognitive impairment, often accompanied by gait disturbances and neuropsychiatric symptoms that remain underrecognized. Age and hypertension are key risk factors, but emerging evidence points to the influence of genetic polymorphisms and clonal hematopoieses. The pathophysiology of CSVD is closely linked to neuroimaging features, as outlined in the Standards for Reporting Vascular changes on neuroimaging (STRIVE) criteria, which reflect the two most prevalent mechanisms: arteriosclerosis and cerebral amyloid angiopathy. As a clinico-radiological syndrome, CSVD encompasses imaging and histopathological findings. Despite its burden on function and quality of life, treatment remains limited to risk factor control. Ongoing studies aim to clarify the underlying mechanisms, validate biomarkers and identify novel therapeutic targets.

Aging drives molecular changes that impair cellular and tissue function. Lipids are central to membrane structure, signaling and energy storage, yet their remodeling during aging remains unclear. Here, using cross-species, multi-tissue lipidomics, we identify elongation of lipid acyl chains as a conserved hallmark of aging across mice, Caenorhabditis elegans, Drosophila and humans. Similar lengthening occurs during the progression of human heart disease, whereas dietary restriction shortens cardiac lipids in mice. Integrated analyses reveal that aging is characterized by a shift toward longer lipids accompanied by depletion of shorter species, indicating ratiometric remodeling. Following this, we identify the lipid remodeler Plb1 as a regulator of this process, with expression correlating with lifespan in mice and genetic analyses supporting a causal role in human frailty. In C. elegans, Plb1 knockdown reverses lipid elongation and extends lifespan in a lipid-length-dependent manner. Together, these findings establish lipid chain length remodeling as a conserved, actionable hallmark of aging.

Myocardial remodeling, an essential pathological development in cardiovascular disease, is largely determined by disruptions in redox homeostasis and mitochondrial bioenergetic function. Iristectorigenin A (ITG), a naturally occurring isoflavone, exhibits a variety of pharmacological effects, including antioxidant and anti-inflammatory activities. While so many protective effects, its specific effect on cardiac remodeling has not been reported previously. In this study, we aims to investigate the role of ITG in pressure overload-induced cardiac remodeling with a particular focus on mitochondrial function and oxidative stress. We revealed that ITG mitigated TAC-induced cardiac remodeling and improved cardiac function, with the 20 mg/kg dose showing optimal efficacy; further escalation to 40 mg/kg provided no additional benefit. ITG attenuated cardiomyocyte hypertrophy and inhibited activation of fibroblasts in vitro. Additionally, ITG treatment effectively suppressed oxidative stress and inflammation in the hearts of TAC mice, while improving mitochondrial morphology and the integrity of inner membrane structure. Notably, surface plasmon resonance (SPR) analysis indicated a direct interaction between SIRT6 and ITG with micromolar affinity. Besides, sustained TAC- or PE-stimulation impaired cardiac sirtuin 6 (SIRT6) protein levels, which were partially reversed by ITG. More importantly, silencing SIRT6 and SIRT6 knockdown separately inhibited the protective effects of ITG in vitro and in vivo. Mechanistically, ITG promotes SIRT6 levels by inhibiting its ubiquitination degradation. Furthermore, the cardioprotective effect of ITG was concomitant with SIRT6 upregulation, deacetylation and dephosphorylation of forkhead box protein O1 (FOXO1) and the subsequent increased transcription of antioxidant genes. Collectively, we firstly discover that ITG inhibits oxidative stress and safeguards mitochondrial morphofunctional homeostasis in response to pathological stress through activating SIRT6/FOXO1 axis, suggesting the therapeutic potential of ITG in the treatment of cardiac hypertrophy and remodeling, providing a promising avenue for future research and potential clinical application. Schematic illustration of ITG's potential protective mechanism against cardiac hypertrophy.

Major adverse cardiovascular events (MACE) are a leading cause of noncancer death in men with prostate cancer (PCa). Androgen receptor pathway inhibitors (ARPIs) improve oncologic outcomes but may exacerbate cardiovascular risk. The Systematic Coronary Risk Evaluation 2(SCORE2) estimates 10-yr cardiovascular risk, yet its validity in men receiving treatment for PCa is untested.

To evaluate the cardiovascular safety of ARPIs and other treatment intensification strategies within the STAMPEDE trial and assess SCORE2 performance.

This post hoc analysis included patients allocated to the abiraterone acetate plus prednisolone (AAP), AAP plus enzalutamide (ENZ), docetaxel (DOC), zoledronic acid (ZA), and radiotherapy (RT) comparisons in STAMPEDE with linked health care records in England.

Treatment intensification with AAP, AAP plus ENZ, DOC, ZA, or prostate RT in addition to standard-of-care androgen deprivation therapy (ADT).

MACE were identified using prespecified International Classification of Diseases, 10th Revision, and Office of Population Censuses and Surveys Classification of Interventions and Procedures codes. Flexible parametric competing-risk models estimated cumulative incidence and subdistribution hazard ratios (SDHRs). SCORE2 discrimination and calibration were evaluated.

A total of 6292 men were included. The 5-yr cumulative MACE incidence with ARPI intensification was 9% in nonmetastatic (M0) disease and 7% in metastatic (M1) disease, comparable to ADT alone. ARPI intensification was not associated with a statistically significant increase in MACE risk (AAP: M0 SDHR 1.15 [95% confidence interval {CI} 0.80-1.67], M1 SDHR 1.36 [95% CI 0.87-2.10]; AAP plus ENZ: M0 SDHR 1.34 [95% CI 0.91-1.98], M1 SDHR 1.28 [95% CI 0.85-1.94]). Cardiovascular disease history was the strongest predictor of MACE. Among 5076 patients eligible for SCORE2 assessment, 4239 had complete baseline data. SCORE2 discrimination was modest (10-yr area under the curve 0.63 for M0 disease and 0.61 for M1 disease), and absolute cardiovascular risk was underestimated. Limitations included underrepresentation of patients with severe cardiovascular comorbidity.

No statistically significant increase in MACE was observed with ARPIs, DOC, ZA, or prostate RT compared with ADT alone. SCORE2 underestimated cardiovascular risk, supporting development of PCa-specific cardiovascular risk models.