Does ICU admission dysphagia independently contribute to delirium risk in ischemic stroke patients? Results from a cohort study.

BACKGROUND: Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. METHODS: A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. RESULTS: The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). CONCLUSION: ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.

Potential prognostic value of CSF-targeted proteomics across the Alzheimer's disease continuum.

BACKGROUND: Core biomarkers for Alzheimer's disease (AD), such as Aß42 and tau, have demonstrated high prognostic accuracy but do not fully capture the complex pathophysiology of AD. In this study, our objective was to identify novel cerebrospinal fluid (CSF) biomarkers using proteomics across the entire AD continuum to predict conversion to AD and explore their involvement in AD pathogenesis. METHODS: A cohort of 186 cognitively normal (CN), 127 subjective memory complaint (SMC), 79 early mild cognitive impairment (EMCI), 249 late MCI (LMCI), and 132 AD individuals was analyzed, with a follow-up period of over 3 years for non-AD participants. CSF 65 peptides, as well as hippocampal and entorhinal volumes were analyzed, and cognitive function was evaluated using the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 13). Cox proportional hazards models and mediation analysis were performed to investigate associations and causal relationships. RESULTS: During the follow-up, approximately one-fourth (146/580) of the non-AD participants progressed to AD. After adjusting for baseline diagnosis (CN to LMCI) and other variables, multivariable Cox regression analysis identified three peptides (VAELEDEK, VSFELFADK, and VVSSIEQK) as significant predictors of conversion to AD. Incorporating these three peptides into the initial model significantly improved the C-statistic from 0.82 to 0.85 for predicting AD conversion, surpassing the predictive ability of Aß42 and P-tau. Moreover, hippocampal and entorhinal volumes mediated 30.3-53.8% of the association between the three peptides and ADAS-Cog 13 scores. CONCLUSIONS: These findings underscore the potential of these three peptides as robust prognostic biomarker candidates for AD conversion across the entire AD continuum, with a mechanism involving the mediation of hippocampal and entorhinal volumes.

Braden score predicts 30-day mortality risk in patients with ischaemic stroke in the ICU: A retrospective analysis based on the MIMIC-IV database.

BACKGROUND: Ischaemic stroke remains a significant global health challenge, associated with high mortality rates. While the Braden Scale is traditionally employed to assess pressure ulcer risk, its potential to predict mortality among the intensive care unit (ICU) patients with ischaemic stroke has not been thoroughly investigated. AIM/S: This study evaluates the predictive value of the Braden Scale for 30-day mortality among patients with ischaemic stroke admitted to ICU. STUDY DESIGN: We conducted a retrospective analysis of 4710 adult patients with ischaemic stroke from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The association between the Braden Scale scores and 30-day mortality was assessed using receiver operating characteristic (ROC) curve analysis, Cox regression models and Kaplan-Meier survival estimates. RESULTS: Patients with Braden Scale scores ≤ 15.5 showed significantly higher 30-day mortality rates (p-value < 0.001; hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.71-2.53). The area under the ROC curve (AUC) was 0.71, demonstrating good predictive performance. Multivariate analysis confirmed the Braden Scale as an independent predictor of mortality, after adjusting for age, gender and comorbidities. CONCLUSIONS: The Braden Scale effectively identifies high-risk ischaemic stroke patients in ICU settings, endorsing its integration into routine assessments to facilitate early intervention strategies. RELEVANCE TO CLINICAL PRACTICE: Integrating the Braden Scale into routine ICU evaluations can enhance mortality risk stratification and improve patient care tailoring.

Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study.

BACKGROUND: The triglyceride-glucose index (TyG), an established indicator of insulin resistance, is closely correlated with the prognosis of several metabolic disorders. This study aims to investigate the association between the TyG index and the incidence of critical delirium in patients aged 65 years and older. METHODS: We focused on evaluating patients aged 65 years and older diagnosed with critical delirium. Data were obtained from the Medical Information Database for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression and restricted cubic spline (RCS) regression were used to determine the relationship between the TyG index and the risk of delirium. RESULTS: Participants aged 65 years and older were identified from the MIMIC-IV (n = 4,649) and eICU-CRD (n = 1,844) databases. Based on optimal thresholds derived from RCS regression, participants were divided into two cohorts: Q1 (< 8.912), Q2 (≥ 8.912). The logistic regression analysis showed a direct correlation between the TyG index and an increased risk of critical delirium among ICU patients aged 65 and older. These findings were validated in the eICU-CRD dataset, and sensitivity analysis further strengthened our conclusions. In addition, the subgroup analysis revealed certain differences. CONCLUSION: This study highlights a clear, independent relationship between the TyG index and the risk of critical delirium in individuals aged 65 years and older, suggesting the importance of the TyG index as a reliable cardio-cerebrovascular metabolic marker for risk assessment and intervention.

Associations of screen-based sedentary activities with all cause dementia, Alzheimer's disease, vascular dementia: a longitudinal study based on 462,524 participants from the UK Biobank.

BACKGROUND: Current drug treatments for dementia aren't effective. Studying gene-environment interactions can help develop personalized early intervention strategies for Alzheimer's disease (AD). However, no studies have examined the relationship between screen-based sedentary activities and genetic susceptibility to AD risk, and further understanding of the causal relationship is also crucial. METHODS: This study included 462,524 participants from the UK Biobank with a follow-up of 13.6 years. Participants' screen-based sedentary activities time was categorized into three groups based on recorded time: ≥ 4 h/day, 2-3 h/day, and ≤ 1 h/day. Cox proportional risk models were used to analyze the association between computer use/TV viewing groups and the risk of all-cause dementia, AD and vascular dementia (VD). Generalized linear model (GLM) were used to examine the relationship between screen-based sedentary activities and brain structure. Bidirectional Mendelian randomization (MR) was used to validate the causal relationship between TV viewing and AD. RESULTS: Compared to TV viewing ≤ 1 h/day, 1)TV viewing 2-3 h/day was correlated with a higher risk of all-cause dementia (HR = 1.09, 95% CI:1.01-1.18, P < 0.05), and TV viewing ≥ 4 h/day was associated with a higher risk of all-cause dementia (HR = 1.29, 95% CI: 1.19-1.40, P < 0.001), AD (HR = 1.25, 95% CI:1.1-1.42, P < 0.001), and VD (HR = 1.24, 95% CI: 1.04-1.49, P < 0.05); 2) TV viewing ≥ 4 h/day was correlated with a higher AD risk at intermediate (HR = 1.34, 95% CI: 1.03-1.75, P < 0.001) and high AD genetic risk score (AD-GRS) (HR = 2.18, 95% CI: 1.65-2.87, P < 0.001);3) TV viewing 2-3 h/day [ß = (-94.8), 95% CI: (-37.9) -(-151.7), P < 0.01] and TV viewing ≥ 4 h/day [ß = (-92.94), 95% CI: (-17.42) -(-168.46), P < 0.05] were correlated with a less hippocampus volume. In addition, a causal effect of TV viewing times was observed on AD analyzed using MR Egger (OR = 5.618, 95%CI:1.502-21.013, P < 0.05). CONCLUSIONS: There was a causal effect between TV viewing time and AD analyzed using bidirectional MR, and more TV viewing time exposure was correlated with a higher AD risk. Therefore, it is recommended that people with intermediate and high AD-GRS should control their TV viewing time to be less than 4 h/ day or even less than 1 h/day.

Can admission Braden skin score predict delirium in older adults in the intensive care unit? Results from a multicenter study.

AIMS AND OBJECTIVES: To investigate whether a low Braden Skin Score (BSS), reflecting an increased risk of pressure injury, could predict the risk of delirium in older patients in the intensive care unit (ICU). BACKGROUND: Delirium, a common acute encephalopathy syndrome in older ICU patients, is associated with prolonged hospital stay, long-term cognitive impairment and increased mortality. However, few studies have explored the relationship between BSS and delirium. DESIGN: Multicenter cohort study. METHODS: The study included 24,123 older adults from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and 1090 older adults from the eICU Collaborative Research Database (eICU-CRD), all of whom had a record of BSS on admission to the ICU. We used structured query language to extract relevant data from the electronic health records. Delirium, the primary outcome, was primarily diagnosed by the Confusion Assessment Method for the ICU or the Intensive Care Delirium Screening Checklist. Logistic regression models were used to validate the association between BSS and outcome. A STROBE checklist was the reporting guide for this study. RESULTS: The median age within the MIMIC-IV and eICU-CRD databases was approximately 77 and 75 years, respectively, with 11,195 (46.4%) and 524 (48.1%) being female. The median BSS at enrollment in both databases was 15 (interquartile range: 13, 17). Multivariate logistic regression showed a negative association between BSS on ICU admission and the prevalence of delirium. Similar patterns were found in the eICU-CRD database. CONCLUSIONS: This study found a significant negative relationship between ICU admission BSS and the prevalence of delirium in older patients. RELEVANCE TO CLINICAL PRACTICE: The BSS, which is simple and accessible, may reflect the health and frailty of older patients. It is recommended that BSS assessment be included as an essential component of delirium management strategies for older patients in the ICU. NO PATIENT OR PUBLIC CONTRIBUTION: This is a retrospective cohort study, and no patients or the public were involved in the design and conduct of the study.

Clinical features of Trousseau's syndrome with multiple acute ischemic strokes.

BACKGROUND: Trousseau's syndrome or migrating thrombophlebitis can cause venous or arterial thrombosis; however, multiple acute ischemic strokes (MAIS) caused by Trousseau's syndrome are rare. The aim of this study was to analyse the clinical features of Trousseau's syndrome with MAIS and to improve the awareness and the knowledge of this disease. METHODS: Clinical data from fifteen patients who were diagnosed as Trousseau's syndrome with MAIS in Rizhao People's Hospital from January 2017 to April 2020 were collected and analysed. The clinical data included the following: patients' basic information (including gender, age, underlying diseases, and tumour stage), laboratory results, imaging features, treatment regimens, and short-term prognoses were collected. RESULTS: The mean age was 65.5 years, with thirteen males and two females. Most patients (11/15) had a history of smoking and (or) drinking. The average score of NIHSS was 2.13. 6 of the 15 patients first presented with ischemic stroke and then found the primary tumour. Most common types of primary tumour was lung cancer (11/15), and other types of primary tumour were gastric adenocarcinoma, renal cell carcinoma, oesophageal adenosquamous carcinoma, and cholangiocarcinoma (one in each). All the 15 patients showed different levels of increase of D-dimer. The increase in CRP appears in 10 of the 15 patients. Various tumour markers were increased in the 15 patients, especially for CYFRA-211, all the patients of which were higher than normal. All of the 15 patients had multiple vascular territory lesions in DWI, and most lesions were near the cortex areas. Only 4 of the 15 patients (26.7%) occurred with peripheral venous thrombosis. Thirteen patients were given low molecular heparin for anticoagulant therapy, of which 9 patients were improved in short-term while 4 patients were not. CONCLUSION: Trousseau's syndrome with MAIS was associated with old-age male, smoking and (or) drinking history, low NIHSS score, increased D-dimer, CRP and tumour markers, and lesions near the cortex areas with multiple vascular territories in DWI. Patients with these features should be alert of malignant tumour. Most common types of primary tumour were lung cancer. Treatment with low molecular heparin may be effective in short term.

The Hemoglobin-to-Red Cell Distribution Width Ratio to Predict All-Cause Mortality in Patients with Sepsis-Associated Encephalopathy in the MIMIC-IV Database.

Objective: The hemoglobin-to-red cell distribution width ratio (HRR) is associated with the prognosis of sepsis-associated encephalopathy (SAE). This study aimed to determine the relationship between HRR and SAE and to clarify the possible mechanism of HRR as a prognostic factor for SAE. Methods: A multivariate Cox proportional-hazards regression model was used to assess the correlation between HRR and all-cause mortality. Piecewise linear regression and smooth-curve Cox proportional-hazards regression models were used to observe whether there was a nonlinear relationship between HRR and all-cause mortality in SAE. Results: This study included 8853 patients with SAE. A nonlinear relationship between HRR and SAE was observed through a two-segment regression model. The left inflection point for the HRR threshold was calculated to be 15.54, which was negatively correlated with all-cause mortality (HR = 0.83, 95% CI = 0.76-0.91, p < 0.001). Subgroup analyses revealed significant interactions between white blood cell count, glucose, and patients who received dialysis and HRR. The inverse correlation between HRR and SAE was more pronounced in patients who did not receive vasopressin (HR = 0.91, 95% CI = 0.87-0.96, p < 0.001) than in those who did receive vasopressin (HR = 0.94, 95% CI = 0.88-1.02, p=0.152) and was significantly more pronounced in patients without myocardial infarction (HR = 0.91, 95% CI = 0.88-0.96, p < 0.001) than in those with myocardial infarction (HR = 0.94, 95% CI = 0.87-1.02, p < 0.114). Conclusion: This large retrospective study found a nonlinear relationship between all-cause mortality and HRR in patients with SAE in intensive care units, with low HRR being inversely associated with increased all-cause mortality in patients with SAE.

Feelings of tense and risk of incident dementia: A prospective study of 482,360 individuals.

BACKGROUND: The relationship between feelings of tense, as a significant emotional distress, and dementia remains unclear. This study aimed to evaluate the association between feelings of tense and dementia. METHODS: In UK Biobank, feelings of tense were measured with a standard item. The primary outcome was all cause of dementia (ACD) and its subtypes (Alzheimer's disease (AD), vascular dementia (VD), and other dementia). Cox regression models analyzed the association between feelings of tense and dementia risk, while linear regression examined the correlation with neuroimaging outcomes. The potential association and joint effects of AD and tenseness were evaluated based on the established genetic risk score (GRS). RESULTS: During a median follow-up of 12.7 years among 482,360 participants, 7331 dementia cases were identified. Individuals with feelings of tense had a significantly increased risk of ACD (HR, 1.194; 95 % CI: 1.115-1.278), VD (HR, 1.164; 95 % CI: 1.007-1.346), and other dementia (HR, 1.181; 95 % CI: 1.081-1.289), but not AD in multi-adjusted models. This association persisted across various sensitivity analyses and exhibited some heterogeneity in subgroup analyses. Furthermore, feelings of tense are associated with total brain volume shrinkage, higher white matter hyperintensities, and decreased partial subcortical volume, particularly in the hippocampus. No interaction between tenseness and AD genetic susceptibility was observed (P for interaction =0.346). LIMITATIONS: Our study only considered feelings of tense measured at a one-time point. CONCLUSIONS: Our findings demonstrate a significant association between feeling of tense and elevated dementia risk, indicating that tenseness could serve as a modifiable psychological determinant for dementia.

Associations of Folate/Folic Acid Supplementation Alone and in Combination With Other B Vitamins on Dementia Risk and Brain Structure: Evidence From 466 224 UK Biobank Participants.

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466 224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] = 1.34, 95% confidence interval [CI] = 1.06-1.69, p = .015) and VD (HR = 1.61, 95% CI = 1.21-2.13, p = .001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (ß = -95.25 mm3, 95% CI = -165.31 to -25.19 mm3, p = .014) and amygdala (ß = -51.85 mm3, 95% CI = -88.02 to -15.68 mm3, p = .012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p > .05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.

Dietary inflammatory index, genetic susceptibility and risk of incident dementia: a prospective cohort study from UK biobank.

BACKGROUND: Genetic factors, diet and inflammation are associated with the development of dementia. In this study, we aimed at evaluating the impact of the dietary inflammatory index (DII) scores and genetic susceptibility on the development of dementia. METHODS: This prospective study involved 207,301 participants aged between 39 and 72 years from UK biobank. A web-based 24-h dietary questionnaire was collected at least once from participants between 2006 and 2012. The DII was calculated based on inflammatory effect score of nutrients. Individual AD-GRS (Alzheimer's disease genetic risk score) was calculated. Incident dementia was ascertained through hospital or death records. RESULTS: Of all 207,301 participants, 468 incident cases of all-cause dementia (165 AD, 91 VD and 26 FTD) were reported during a follow-up period of 11.4 years. The participants in the highest quintile (Q) of DII scores reported a higher risk for all-cause dementia (Q5 vs. Q3, hazard ratio (HR) = 1.702; 95% CI: 1.285-2.255) and VD (Q5 vs. Q3, HR = 2.266, 95% CI: 1.133-4.531) compared to participants in the Q3. Besides, when compared with the Q1, there was a higher risk for AD in the subjects of Q5 (Q5 vs. Q1, HR = 1.590; 95% CI: 1.004-2.519). There was a non-linear relationship between DII score and all-cause incidence (P for non-linear = 0.038) by restricted cubic splines. Subgroup analysis found that the increased risk for all-cause dementia and AD was more pronounced in the elderly, women, and higher educated population. Cox regression models indicated that compared with the participants who had a low AD-GRS risk and in the lowest tertile of DII, participants had a high AD-GRS and the highest tertile of DII were associated with a higher risk of AD (HR = 1.757, 95% CI: 1.082-2.855, P = 0.023). CONCLUSIONS: The DII scores were independently associated with an augmented risk for all-cause dementia, AD and VD. Additionally, high AD-GRS with higher DII scores was significantly associated with a higher risk of AD.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank.

OBJECTIVE: To investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. METHODS: This study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2-3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. RESULTS: 1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01-1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05-1.27, P < 0.01), and the 2-3 NSAIDs group (HR = 1.2, 95% CI:1.08-1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2-3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08-1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03-1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07-1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. CONCLUSION: In individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

Association of birthweight and risk of incident dementia: a prospective cohort study.

Given the epidemiological studies investigating the relationship between birthweight and dementia are limited. Our study aimed to explore the association between birthweight and the risk of dementia, cognitive function, and brain structure. We included 275,648 participants from the UK Biobank, categorizing birthweight into quartiles (Q1 ≤ 2.95 kg; Q2 > 2.95 kg, ≤ 3.32 kg; Q3 > 3.32 kg, ≤ 3.66 kg; Q4 > 3.66 kg), with Q3 as the reference. Cox regression models and restricted cubic splines estimated the relationship between birthweight and the risk of all causes of dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Multivariable linear regression models assessed the relationship between birthweight, cognitive function, and MRI biomarkers. Over a median follow-up of 13.0 years, 3103 incident dementia cases were recorded. In the fully adjusted model, compared to Q3 (> 3.32 kg, ≤ 3.66 kg), lower birthweight in Q1 (≤ 2.95 kg) was significantly associated with increased risk of ACD (HR = 1.18, 95%CI 1.06-1.30, P = 0.001) and VD (HR = 1.32, 95%CI 1.07-1.62, P = 0.010), but no significant association with AD was found. Continuous birthweight showed a U-shaped nonlinear association with dementia. Lower birthweight was associated with worse performance in cognitive tasks, including reaction time, fluid intelligence, numeric, and prospective memory. Additionally, certain brain structure indices were identified, including brain atrophy and reductions in area, thickness, and volume of regional subcortical areas. Our study emphasizes the association between lower birthweight and increased dementia risk, correlating cognitive function and MRI biomarkers of brain structure, suggesting that in utero or early-life exposures might impact cognitive health in adulthood.

The circular RNA hsa_circ_0045800 serves as a favorable biomarker in pathogenesis of sjögren's syndrome.

BACKGROUND: Circular RNAs (circRNAs) play various roles in the development of many autoimmune diseases. However, their expression profiles and specific function in Sjögren's Syndrome remains largely unknown. OBJECTIVES: We aimed to investigate circRNAs potential diagnostic value in primary Sjögren's syndrome (pSS) and contribution to the pathogenesis of pSS. METHODS: This study included 102 subjects, 51 pSS patients and 51 healthy controls. The concentration of hsa_circ_0045800 was analyzed in peripheral blood mononuclear cells obtained from 51 pSS patients and 51 healthy controls by qRT-PCR. We established a receiver operating characteristic curve (ROC) to assess the biological diagnostic value of hsa_circ_0045800 for pSS. In addition, we analyzed the correlation between hsa_circ_0045800 and disease activity in Sjogren's syndrome. A differential analysis was also conducted on the concentration of hsa_circ_0045800 in patients in pSS patients before and after treatment. We studied the downstream mechanism of hsa_circ_0045800 through bioinformatics analysis and confirmed it using luciferase reporter gene assay. RESULTS: We confirmed that the concentration of hsa_circ_0045800 was elevated 10.4-fold in peripheral blood mononuclear cells of pSS patients than in healthy controls (p = 0.00). In the pSS active disease group, the concentration of hsa_circ_0045800 is 2.5-fold higher compared to the pSS non-active disease group (p = 0.04). The concentration of hsa_circ_0045800 after treatment was decreased by 80% compared with that before treatment (p = 0.037), suggesting its utility as a potential marker for monitoring treatment efficacy. ROC curve analysis showed that the diagnostic value of hsa_circ_0045800 in pSS patients was significantly higher than that in healthy controls, with an area under the curve of 0.865, a sensitivity of 74%, and a specificity of 92%. The concentration of hsa_circ_0045800 is correlated with various clinical factors: the concentration of hsa_circ_0045800 is positively associated with age (r = 0.328, P = 0.019), oral dryness (r = 0.331, P = 0.017), while it is negatively correlated with HGB (r = -0.435, P = 0.001) and and hypothyroidism (r = -0.318, P = 0.023). Bioinformatics predictions and luciferase assays indicated that hsa_circ_0045800 acts as a molecular sponge for miR-1247-5p, with SMAD2 being a target gene of miR-1247-5p. CONCLUSION: Our study results show that hsa_circ_0045800 potentially contributes to the development and progression of pSS via the miR-1247-5p/SMAD2 pathway. Peripheral blood mononuclear cells are directly involved in the pathogenesis of pSS, and the discovery of hsa_circ_0045800 in peripheral blood mononuclear cells highlights its potential as a novel biomarker for disease activity and diagnosis in patients with pSS. Key Points • The concentration of hsa_circ_0045800 was higher in peripheral blood mononuclear cells of pSS patients. • Hsa_circ_0045800 promoted pSS progression through miR-1247-5p-SMAD2 axis. • Hsa_circ_0045800 is a potential biomarker for pSS.

Association between modified frailty index and postoperative delirium in patients after cardiac surgery: A cohort study of 2080 older adults.

AIM: To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients. METHODS: A retrospective study was conducted of older patients admitted to the intensive care unit after cardiac surgery at a tertiary academic medical center in Boston from 2008 to 2019. Frailty was measured using the Modified Frailty Index (MFI), which categorized patients into frail (MFI ≥3) and non-frail (MFI = 0-2) groups. Delirium was identified using the confusion assessment method for the intensive care unit and nursing notes. Logistic regression models were used to examine the association between frailty and POD, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 2080 patients included (median age approximately 74 years, 30.9% female), 614 were frail and 1466 were non-frail. The incidence of delirium was significantly higher in the frail group (29.2% vs. 16.4%, p < 0.05). After adjustment for age, sex, race, marital status, Acute Physiology Score III (APSIII), sequential organ failure assessment (SOFA), albumin, creatinine, hemoglobin, white blood cell count, type of surgery, alcohol use, smoking, cerebrovascular disease, use of benzodiazepines, and mechanical ventilation, multivariate logistic regression indicated a significantly increased risk of delirium in frail patients (adjusted OR: 1.61, 95% CI: 1.23-2.10, p < 0.001, E-value: 1.85). CONCLUSIONS: Frailty is an independent risk factor for POD in older patients after cardiac surgery. Further research should focus on frailty assessment and tailored interventions to improve outcomes.

Delirium Mediated the Association Between a History of Falls and Short-Term Mortality Risk in Critically Ill Ischemic Stroke Patients.

Patients with ischemic stroke have an increased propensity to fall, resulting in significant physical and psychological distress. This study examined the association between falls in the 3 months prior to intensive care unit (ICU) admission and mortality within 28 days among 2950 adult ICU patients diagnosed with ischemic stroke from 2008 to 2019, focusing on the potential mediating role of delirium. The primary outcomes were short-term mortality (28, 60, and 90 days) and the risk of delirium. Each patient was followed for at least 1 year. Delirium was primarily assessed using the Confusion Assessment Method for the ICU and by reviewing nursing notes. Group differences between patients with and without a history of falls were compared using the Wilcoxon rank-sum test or the chi-squared test. Cox proportional risk or logistic regression models were used to explore the association between fall history and outcomes, and causal mediation analysis was performed. Results showed that patients with a recent fall history had a significantly increased risk of 28-day (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.35-1.94), 60-day (HR: 1.67, 95% CI: 1.42-1.98), and 90-day mortality (HR: 1.66, 95% CI: 1.41-1.95), as well as an increased risk of delirium (odds ratio: 2.00, 95% CI: 1.66-2.42). Delirium significantly mediated the association between fall history and 28-day mortality (total effect: HR: 1.77, 95% CI: 1.45-2.16; natural indirect effect: HR: 1.12, 95% CI: 1.05-1.21; proportion mediated: 24.6%). These findings suggest that ischemic stroke patients with a recent fall have an increased risk of short-term mortality, partly mediated by delirium. Strategies aimed at preventing delirium may potentially improve prognosis in this patient population.

Association between probable sarcopenia and dementia risk: a prospective cohort study with mediation analysis.

The role of alcohol consumption as a mediator in the risk between sarcopenia and dementia remains inadequately studied. There is currently limited research on whether the association between sarcopenia and the risk of Alzheimer's disease (AD) is influenced by genetic susceptibility. Our study incorporated a total of 483,637 baseline non-dementia participants, who were classified into groups of individuals with no sarcopenia and those with probable sarcopenia based on the definition. We employed Cox proportional hazards models to evaluate the association between probable sarcopenia and the risk of all cause dementia (ACD), AD, and vascular dementia (VD). We conducted mediation analysis to explore the role of alcohol consumption in the association between probable sarcopenia and the risk of ACD, AD, and VD. During the median follow-up period of 13.6 years, we documented 9000 new cases of ACD (including 4061 AD and 2025 VD). Fully adjusted multivariate model revealed a significant correlation between probable sarcopenia and elevated risk for ACD (HR = 1.54, 95% CI: 1.46-1.62, p < 0.001), AD (HR = 1.32, 95% CI: 1.21-1.43, p < 0.001), and VD (HR = 1.69, 95% CI: 1.52-1.89, p < 0.001). Mediation analysis elucidates that alcohol consumption explained 12.8%, 15.2%, and 11.1% of the associations of probable sarcopenia with the risk of ACD, AD, and VD, respectively. An interactive relationship prevails between probable sarcopenia and genetic factors (p for interaction <0.001), and regardless of the degree of genetic risk, probable sarcopenia correlates with an elevated AD risk. Our study reveals a significant association between probable sarcopenia and an increased risk of dementia, with alcohol consumption playing a mediating role in this association. There is an interaction between probable sarcopenia and genetic susceptibility related to the risk of AD.

ICU admission Braden score independently predicts delirium in critically ill patients with ischemic stroke.

BACKGROUND: Delirium is a common and severe complication in intensive care unit (ICU) patients with acute ischemic stroke, exacerbating cognitive and physical impairments. It prolongs hospitalization, increases healthcare costs, and raises mortality risk. Early prediction is crucial because it facilitates prompt interventions that could possibly reverse or alleviate the detrimental consequences of delirium. Braden scores, traditionally used to assess pressure injury risk, could also signal frailty, providing an early warning of delirium and aiding in prompt and effective patient management. OBJECTIVE: To examine the association between the Braden score and delirium. METHODS: A retrospective analysis of adult ischemic stroke patients in the ICU of a tertiary academic medical center in Boston from 2008 to 2019 was performed. Braden scores were obtained on admission for each patient. Delirium, the primary study outcome, was assessed using the Confusion Assessment Method for Intensive Care Unit and a review of nursing notes. The association between Braden score and delirium was determined using Cox proportional hazards modeling, with hazard ratios (HR) and 95% confidence intervals (CI) calculated. RESULTS: The study included 3,680 patients with a median age of 72 years, of whom 1,798 were women (48.9 %). The median Braden score at ICU admission was 15 (interquartile range 13-17). After adjustment for demographics, laboratory tests, severity of illness, and comorbidities, the Braden score was inversely associated with the risk of delirium (adjusted HR: 0.94, 95 % CI: 0.92-0.96, P < 0.001). CONCLUSIONS: The Braden score may serve as a convenient and simple screening tool to identify the risk of delirium in ICU patients with ischemic stroke. IMPLICATION FOR CLINICAL PRACTICE: The use of the Braden score as a predictor of delirium in ischemic stroke patients in the ICU allows early identification of high-risk patients. This facilitates timely intervention, thereby improving patient outcomes and potentially reducing healthcare costs.

The association of night shift work with the risk of all-cause dementia and Alzheimer's disease: a longitudinal study of 245,570 UK Biobank participants.

BACKGROUND: The purpose of this research was to investigate a possible link between night shift work and the development of all-cause dementia and Alzheimer's disease (AD), as well as determine the contribution of night shift work, genetic susceptibility to AD. METHODS: This study was conducted using the UK Biobank database. 245,570 participants with a mean follow-up length of 13.1 years were included. A Cox proportional hazards model was used to investigate the link between night shift work and the development of all-cause dementia or AD. RESULTS: We counted a total of 1248 participants with all-cause dementia. In the final multivariable adjusted model, the risk of dementia was highest in always night shift workers (HR 1.465, 95% CI 1.058-2.028, P = 0.022), followed by irregular shift workers (HR 1.197, 95% CI 1.026-1.396, P = 0.023). AD events were recorded in 474 participants during the follow-up period. After final multivariate adjustment of model, always night shift workers remained at the highest risk (HR 2.031, 95% CI 1.269-3.250, P = 0.003). Moreover, always night shift workers were associated with a higher risk of AD in both low, intermediate and high AD-GRS groups. CONCLUSIONS: Always night shift work had a higher risk of developing all-cause dementia and AD. Irregular shift workers had a higher risk of developing all-cause dementia than no shift workers. Always night shift work had a higher AD risk, regardless of whether they had a high, intermediate or low AD-GRS.

Associations of air pollution with all-cause dementia, Alzheimer's disease, and vascular dementia: a prospective cohort study based on 437,932 participants from the UK biobank.

Objective: To prospectively assess whether air pollution, including PM2.5, PM10, and NOx, is associated with the risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia, and to investigate the potential relationship between air pollution and genetic susceptibility in the development of AD. Methods and results: Our study included 437,932 participants from the UK Biobank with a median follow-up period of over 10 years. Using a Cox proportional hazards model, we found that participants exposed to PM2.5 levels of ≥10 µg/m3 had a higher risk of developing all-cause dementia (HR = 1.1; 95% CI: 1.05-1.28; p < 0.05) compared to the group exposed to PM2.5 levels of <10 µg/m3. However, there was no significant association between PM10 levels of ≥15 µg/m3 and the risk of all-cause dementia, AD, or vascular dementia when compared to the group exposed to PM10 levels of <15 µg/m3. On the other hand, participants exposed to NOx levels of ≥50 µg/m3 had a significantly higher risk of all-cause dementia (HR = 1.14; 95% CI: 1.02-1.26; p < 0.05) and AD (HR = 1.26; 95% CI: 1.08-1.48; p < 0.05) compared to the group exposed to NOx levels of <50 µg/m3. Furthermore, we examined the combined effect of air pollution (PM2.5, PM10, and NOx) and Alzheimer's disease genetic risk score (AD-GRS) on the development of AD using a Cox proportional hazards model. Among participants with a high AD-GRS, those exposed to NOx levels of ≥50 µg/m3 had a significantly higher risk of AD compared to those in the group exposed to NOx levels of <50 µg/m3 (HR = 1.36; 95% CI: 1.03-1.18; p < 0.05). Regardless of air pollutant levels (PM2.5, PM10, or NOx), participants with a high AD-GRS had a significantly increased risk of developing AD. Similar results were obtained when assessing multiple variables using inverse probability of treatment weighting (IPTW). Conclusion: Our findings indicate that individuals living in areas with PM2.5 levels of ≥10 µg/m3 or NOx levels of ≥50 µg/m3 are at a higher risk of developing all-cause dementia. Moreover, individuals with a high AD-GRS demonstrated an increased risk of developing AD, particularly in the presence of NOx ≥ 50 µg/m3.