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High-Dose vs. Standard-Dose Influenza Vaccine in Heart Failure: A Prespecified Analysis of the DANFLU-2 Trial
Background: Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular (CV) and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose IIV (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and CV disease by HF status remains uncertain. Methods: This was a prespecified analysis of a pragmatic, prospective, individually randomized, open-label trial with registry-based endpoint-evaluation conducted in Denmark across the 2022/2023 to 2024/2025 influenza seasons. Citizens ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Outcomes included hospitalization for influenza-related illness, laboratory-confirmed influenza (LCI), any CV disease, cardio-respiratory disease, and HF, assessed by HF status. Effect of HD-IIV vs. SD-IIV in reducing risk of outcomes assessed was expressed as risk ratios (RR). Results: The trial randomized 332,438 participants (48.6% female, mean age 73.7±5.8 years), including 10,410 with HF at baseline (27.4% female, mean age 76.0±6.3 years). Overall, HD-IIV was associated with a statistically significant lower incidence of hospitalization for influenza-related illness, LCI, cardio-respiratory disease, CV disease, and HF compared with SD-IIV. In participants with HF, effect estimates were similar: RR for influenza-related hospitalization was 0.48 (95%CI, 0.20-1.06; p interaction =0.64), for LCI hospitalization 0.55 (95%CI, 0.29-1.02; p interaction =0.59), for cardio-respiratory hospitalization 0.89 (95%CI, 0.77-1.02; p interaction =0.34), for CV hospitalization 0.86 (95%CI, 0.72-1.02; p interaction =0.34), and for HF hospitalization 0.82 (95%CI, 0.61-1.11; p interaction =0.83). Findings were consistent across HF subgroups by disease duration, recency of hospitalization, most recent N-terminal pro-B-type natriuretic peptide, and presence of device therapy. Conclusions: In this prespecified exploratory analysis of the largest individually randomized influenza vaccine trial ever conducted, HD-IIV was associated with lower rates of influenza and CV hospitalizations compared with SD-IIV, with effect estimates similar across HF status at baseline and HF subgroups.
Association of age at menarche, age at menopause, and reproductive lifespan with frailty index in Chinese adult women
Objective To identify individuals with accelerated aging under the frailty index (FI) as a proxy indicator of biological age, and to investigate the associations of age at menarche, age at menopause, and reproductive lifespan with frailty status and multi-timepoint FI trajectories among Chinese adult women. Methods The current study included 302 471 women from the China Kadoorie Biobank 2004-2008 baseline survey data. Their age at menarche and menopause were self-reported, and the duration of reproductive lifespan was calculated by subtracting the two ages. The baseline FI was constructed using 28 baseline variables, including diseases, symptoms, and anthropometric measurements. Frailty status was categorized into three groups: non-frail (FI≤0.10), pre-frail (0.10
Relationship between ambient air pollution and vitamin D in Chinese adults
Objective To investigate the relationship between individual and combined exposure to ambient air pollutants and vitamin D, as well as the potential role of ultraviolet radiation (UVR) in mediating the relationships. Methods This study included 6 967 participants from the China Kadoorie Biobank, whose baseline (2004-2008) blood 25-hydroxyvitamin D had been tested. The average monthly concentrations of pollutants (PM2.5, PM10, NO2, O3) and the UVR estimates in the month of blood sample collection were derived from the ChinaHighAirPollutants and ultraviolet datasets covering China, respectively. Linear models and multinomial logistic regression models were used to analyze the associations of each air pollutant with vitamin D concentrations and groups. Principal component analysis integrated with quantile-based g-computation was applied to evaluate the co-effects and relative contribution weights of air pollutants. Mediation analyses were performed to investigate the potential role of UVR. Results PM2.5, PM10, NO2, and O3 were individually associated with vitamin D concentrations, as well as vitamin D groups: insufficiency (20-30 ng/ml) and deficiency (<20 ng/ml). For each 10 μg/m³ increase in monthly PM2.5, PM10, NO2, and O3, the percentage changes (95%CIs) in vitamin D concentrations were -1.71% (-2.16% - -1.26%), -1.30% (-1.60% - -1.00%), -3.77% (-4.60% - -2.93%), and 1.27% (0.91%-1.63%), respectively, with corresponding ORs (95%CIs) for vitamin D deficiency of 1.17 (1.06-1.29), 1.12 (1.05-1.19), 1.66 (1.38-2.00), and 0.81 (0.74-0.89). The mixture of the first principal component of PM2.5 and PM10 (PM), along with NO2 and O3, was negatively correlated with vitamin D. The percentage change (95%CI) in vitamin D concentrations for a one-quintile increase in the mixture was -2.20% (-3.56%- -0.82%), with NO2 contributing the most (83%), followed by PM (17%). UVR-mediated association was 12.2% (95%CI：2.5%-23.0%) for PM2.5 and 4.9% (95%CI：2.2%-8.0%) for PM10 with vitamin D concentrations, respectively. Conclusion Higher concentrations of particulate matter, NO2, and a mixture of air pollutants were associated with lower vitamin D concentrations in Chinese adults, with reduced UVR acting as a partial mediator in the particulate matter-vitamin D relationship.
Association between tobacco smoking and the need for respiratory support and mortality in patients hospitalized with pneumonia
Objective To explore the impacts of smoking on the need for respiratory support and mortality in patients hospitalized with pneumonia. Methods A total of 24 367 patients hospitalized with pneumonia from 2009 to 2017 in the China Kadoorie Biobank, were included. Smoking status was self-reported, and data regarding respiratory support during hospitalization and mortality during follow-up were obtained from medical claims and death registries, respectively. OR, HR, and 95%CI were calculated and adjusted for potential confounders using logistic regression models and Cox proportional hazards regression models, respectively. Results Among males, current smokers or those who quit smoking due to illness had higher risks of requiring respiratory support (OR=1.15, 95%CI: 1.03-1.29), 1-year mortality (HR=1.66, 95%CI: 1.32-2.08), and 5-year mortality (HR=1.32, 95%CI: 1.13-1.54) following pneumonia hospitalization compared to nonsmokers. Male smokers who started smoking at a younger age or with longer smoking duration had the highest mortality risks (trend test both P<0.05). Female current smokers or those who quit smoking due to illness had higher risks of 1-year mortality (HR=1.62, 95%CI: 1.17-2.23) and 5-year mortality (HR=1.33, 95%CI: 1.06-1.67). We found no statistically significant difference in 90-day mortality between current smokers/those who quit smoking due to illness and nonsmokers. Conclusions Smoking was associated with higher risks of requiring respiratory support and mortality in patients hospitalized with pneumonia, especially among males and heavy smokers. These findings highlight the need for targeted strategies to promote smoking cessation in patients hospitalized with pneumonia.
Subclinical Postpartum Renal Structure After Hypertensive Pregnancy Disorders.
BACKGROUND: Hypertensive pregnancies are associated with increased risks of renal failure in pregnancy and later life. However, traditional markers of renal function normalize postpartum, making identification of those at future disease risk difficult. We studied whether the type and severity of hypertensive pregnancy associated with postpartum renal structure. METHODS: One hundred twenty-five women from interventional trials (61 preeclamptic, 33 gestational hypertension, and 31 normotensive pregnancy), aged ≥18 years, were imaged using magnetic resonance imaging 6 to 12 months postpartum. Anthropometric, demographic, blood pressure, and blood sample data were collected during pregnancy and postpartum. Kidney volume indexed to body surface area and corticomedullary differentiation were compared between groups using a 1-way ANCOVA, whereas associations with other outcomes were assessed using correlation tests. RESULTS: Postpartum total kidney volume indexed to body surface area was smaller in women who had preeclampsia compared with those who had gestational hypertension or a normotensive pregnancy (P=0.049). Total kidney volume postpartum correlated with estimated glomerular filtration rate at delivery (P<0.001). However, smaller volumes were not explained by reduced corticomedullary differentiation, which only differed in women with gestational hypertension compared with preeclamptic (P=0.02) and normotensive women (P=0.007). There were no associations between renal measures and blood pressure during or after pregnancy. CONCLUSIONS: At 6 to 12 months postpartum, preeclamptic women have smaller kidney volumes than women with gestational hypertension or normotensive pregnancies. These smaller volumes relate to lower renal function at delivery but not corticomedullary differentiation, which only differed in women with gestational hypertension. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04273854 and NCT05434195.
A Symbol of Immortality: Evidence of Honey in Bronze Jars Found in a Paestum Shrine Dating to 530–510 BCE
This study re-examines a 2500-year-old residue found in bronze jars at an underground shrine in Paestum (Italy), previously identified as a wax/fat/resin mixture excluding honey from its composition. Our multianalytical approach detected lipids, saccharide decomposition products, hexose sugars, and major royal jelly proteins supporting the hypothesis that the jars once also contained honey/honeycombs. The research highlights the value of reinvestigating archeological residues in museums with advanced biomolecular techniques and offers a more specific method for detecting bee products in ancient contexts.
Second cancers in 475 000 women with early invasive breast cancer diagnosed in England during 1993-2016: population based observational cohort study.
OBJECTIVE: To describe long term risks of second non-breast primary cancers and contralateral breast cancers among women with early invasive breast cancer after primary surgery. DESIGN: Population based observational cohort study. SETTING: Routinely collected data from the National Cancer Registration and Analysis Service for England. PARTICIPANTS: All 476 373 women with breast cancer as their first invasive (index) cancer registered in England from January 1993 to December 2016 with follow-up until October 2021. MAIN OUTCOME MEASURES: Rates and cumulative risks of subsequent primary cancers, compared with those occurring in the general population; associations with characteristics of patients, index tumours, and adjuvant treatments. RESULTS: Although 64 747 women developed a second primary cancer, the absolute excess risks compared with risks in the general population were small. By 20 years, 13.6% (95% confidence interval 13.5% to 13.7%) of women had developed a non-breast cancer, 2.1% (2.0% to 2.3%) more than expected in the general population, and 5.6% (5.5% to 5.6%) had developed a contralateral breast cancer, 3.1% (3.0% to 3.2%) more than expected. The absolute excess risk of contralateral breast cancer was greater in younger than in older women. Among specific types of non-breast cancer, the largest 20 year absolute excess risks were for uterine and lung cancers. Although for cancers of the uterus, soft tissue, bones and joints, and salivary glands, as well as acute leukaemias, standardised incidence ratios exceeded those of the general population by a factor of at least 1.5, absolute excess risks at 20 years were <1% for every individual non-breast cancer type. When patients were categorised according to adjuvant treatment, radiotherapy was associated with increased contralateral breast and lung cancer, endocrine therapy with increased uterine cancer (but reduced contralateral breast cancer), and chemotherapy with increased acute leukaemia. These were consistent with effects reported in randomised trials, but positive associations for soft tissue, head and neck, ovarian, and stomach cancers were also identified, and these have not previously been observed in trials. This suggested that approximately 2% of all the 64 747 second cancers and 7% of the 15 813 excess second cancers in the cohort may be attributable to adjuvant therapies. CONCLUSIONS: The risk of a second primary cancer in women treated for early invasive breast cancer is slightly higher than for women in the general population. Contralateral breast cancer accounts for around 60% of the overall increase, with higher risks in younger women. The risk associated with adjuvant therapies is small.
Traumatic brain injury induces a sustained sensorimotor impairment associated with a dysregulated acute phase response in mice overexpressing human amyloid precursor protein.
Traumatic brain injury (TBI) significantly contributes to morbidity and mortality worldwide, often leading to cognitive decline. Although there is a recognised link between TBI and the acceleration of Alzheimer's disease (AD), the precise biological mechanisms driving this relationship are not fully understood. While several studies have investigated TBI in AD mouse models, none have examined the role of systemic inflammation in this context. In this study, we investigated the inflammatory responses, both centrally and peripherally, in 1-year-old wild-type (WT) and J20 mice (Tg:PDGFB-APPSwInd), overexpressing human amyloid precursor protein with the Swedish and Indiana mutations. Following controlled cortical impact (CCI) at 0.5 mm depth to the left somatosensory cortex, we examined outcomes at 1 and 7 days post-injury. The J20 mice exhibited a persistent sensorimotor impairment post-TBI, as determined by the adhesive removal test. Although amyloid-β42 deposition progressively increased post-injury, this behavioural deficit was not associated with greater neuronal loss compared to WT mice. Using qPCR, it was revealed that the level of proinflammatory cytokine and chemokine expression in the brain was largely conserved between WT and J20 mice, though brain Cxcl10 expression increased by 28.6 % in J20 mice at 7d-post injury compared to WT. However, J20 mice exhibited an exaggerated acute phase response (APR) to the TBI in the liver and spleen at 7d. Accompanying the potentiated APR, 1H NMR revealed that plasma glucose was decreased in J20 mice compared to WT at 7d. Taken together, this suggests that the sustained sensorimotor deficit in J20 mice is associated with increased amyloid-β pathology, and a dysregulated and prolonged systemic inflammatory response, accompanied by hypoglycaemia. In general, TBI in the presence of AD pathology, results in extended systemic inflammatory and metabolic responses that are likely to underpin the extended cognitive impairment, and our findings emphasise the need for customised interventions that address central and systemic inflammation after TBI in individuals with neurodegenerative disease.
Patterns and correlates of visual impairment and ocular hypertension among older adults in the general Chinese population: results from the CKB Biobank.
BACKGROUND: While numerous ophthalmology-specific cohort studies have been conducted in China, there is a significant lack of comprehensive, population-based study on the potential determinants of visual impairment and ocular hypertension (OHT) in the general Chinese population. METHODS: In the 2020-2021 resurvey of the China Kadoorie Biobank study, ~25 000 randomly selected participants from 10 diverse localities (5 urban and 5 rural) were surveyed. Presenting visual acuity (PVA) was measured using the Random E eye chart and intraocular pressure (IOP) was measured using a handheld Icare (ic100) tonometer. Associations of sociodemographic and other factors with risks of visual impairment and OHT were examined using multivariable logistic regression. RESULTS: Among the 24 613 (aged 45-95 years, 64.4% women) participants, 21.8% had visual impairment (PVA <0.50) and 18.4% had OHT (IOP >18.6 mm Hg). The prevalence rate of visual impairment increased dramatically with age (49.3% in those ≥75 years vs 8.9% in those <55 years), but an opposite trend was observed for OHT. Risks of these two eye conditions were both inversely associated with household income and fish consumption but positively with systolic blood pressure and blood glucose. Higher education was associated with a higher OHT risk but not with visual impairment. Body mass index was inversely associated with visual impairment but positively with OHT. Age-related macular degeneration and glaucoma were most strongly associated with risk of visual impairment, followed by cataract. CONCLUSION: The relatively high prevalence rates of poor vision and OHT in China suggest that well-targeted public health interventions should be developed.
Systematic review and meta-analysis of the importance of pre-pregnancy maternal health on the risk of hypertensive disorders of pregnancy.
Stratifying women using their medical history pre-pregnancy may allow early identification of women at high-risk of Hypertensive disorders of pregnancy (HDP), a common and high-burden obstetrical complication. This would allow the establishment of early preventative approaches, however, most research into pregestational conditions comes from data taken during pregnancy. To address this gap, we conducted a systematic review with meta-analysis, adhering to PRISMA and MOOSE guidelines. Our review comprehensively examined the impact of a broad range of medical disorders exclusively diagnosed pre-pregnancy on the development of HDP, including preeclampsia, gestational hypertension, superimposed preeclampsia, eclampsia and HELLP. We searched Medline (OvidSP) and Embase (OvidSP) databases from inception to 8th May 2021 and calculated relative risks ratios, adjusted for study quality, or percentage incidences. 406/8724 studies were included for qualitative research, 177 of which classified for quantitative assessment. HDP risk increased with pregestational renal conditions (7.76, CI: 5.62-10.71), hypertension (3.68, CI: 1.51-8.97), diabetes (3.57, CI: 2.71-4.70), and high body mass index (2.65, CI: 2.33-3.03); as well as with pregestational polycystic ovarian syndrome (1.90, CI: 1.46-2.48), rheumatoid arthritis (1.54, CI: 1.42-1.67), migraines (1.53, CI: 1.32-1.78), and anxiety/depression (1.52, CI: 1.16-2.00). Pregestational antiphospholipid syndrome, systemic lupus erythematosus, and Takayasu arteritis also increased the incidence of gestational hypertension (8 %, 7 %, 17 %) and preeclampsia (37 %, 17 %, 23 %). Overall, this review shows pre-pregnancy maternal health can help stratify HDP risk, and highlights the importance of often-overlooked risk factors in current national guidelines and assessment tools. Crucially, we provide an evidence-based graphical abstract/list of the identified pregestational risk factors as reference for medical practitioners providing pre-pregnancy counselling.