Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. METHODS: A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. RESULTS: After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16-1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31-1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex (Pinteraction<0.05) and age (Pinteraction<0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43-2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20-1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07-2.25]) and 172% (HR, 2.72 [95% CI, 1.87-3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92-1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men (Pinteraction<0.05) and women (Pinteraction<0.05), but the sex difference in this risk was only present in participants younger than 45 years (Pinteraction<0.05). CONCLUSIONS: MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.

Changes in baPWV and the risk of clinical outcomes: a cohort study of Chinese community-based population.

It has not been fully investigated whether improved arterial stiffness (AS) can reduce the clinical outcomes risk in community population-based study. In this prospective study, a total of 5247 individuals with abnormal AS (at baseline) and repeated brachial-ankle pulse wave velocity (baPWV) measurement before 2018 years were enrolled from the Kailuan Study. According the second baPWV measurement, we divided the participants into two groups, improved AS (defined as transfer elevated AS status to normal) and persistent AS (defined as maintaining elevated AS status). The outcome was a composite event of stroke, myocardial infraction, and all-cause mortality. We used Cox proportional hazards regression to examine the association between AS status at the follow-up and the subsequent outcome. During a median of 5.2 years follow-up, we observed 413 end point events. After adjusted for potential confounders, comparing with the persistent AS group, individuals in the improved AS group had a 43% (hazard ratio [HR], 0.57; 95% confidence interval [CI] 0.35-0.94) decreased the risk of the primary composite events. We also found a baPWV decrease of 1 m/s was associated with a 3% decreased risk (HR, 0.97; 95% CI 0.94-0.99) for primary composite events. We further demonstrated that younger than 60 years, non-smoker, non-hypertension, and non-diabetes were associated with improved the AS status. In conclusion, improving AS status may reduce the risk of clinical events. In the future, more research should be performed to explore the target for improving the AS status.

Association of Stroke With Metabolic Dysfunction-Associated Fatty Liver Disease With and Without CKD.

RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.

Association of Vascular Aging With Cardiovascular Disease in Middle-Aged Chinese People: A Prospective Cohort Study.

Background: Whether middle-aged individuals with a greater difference between chronological age and vascular age show a lower cardiovascular disease risk remains to be clarified. Objectives: This study sought to examine whether individuals with supernormal vascular aging (VA) have a lower cardiovascular disease risk than do individuals with normal VA. Methods: This prospective cohort study included 20,917 middle-aged (40-60 years) participants from the Kailuan Study. VA was defined as the predicted age in a multivariate regression model, including classic cardiovascular risk factors and pulsed wave velocity. The chronological age minus the VA was defined as the Δ-age, and the 10th and 90th percentiles of the Δ-age were used as cutoffs to define early VA and supernormal VA, respectively. The outcome was a composite of myocardial infarction, hospital admission for heart failure, and stroke. The study used Cox proportional hazards regression to examine the association between the VA categories and the incident cardiovascular outcome. Results: During the median 4.6-year follow-up period, 584 endpoint events were observed. After adjusting for potential variables, when compared with the normal VA group, the supernormal VA group had a decreased rate of cardiovascular events (HR: 0.47; 95% CI: 0.35-0.64), and the early VA group had an increased rate (HR: 1.90; 95% CI: 1.22-2.95) of cardiovascular events. Conclusions: Individuals with supernormal VA are at a lower risk of cardiovascular events, and individuals with early VA are at a higher risk of cardiovascular events than individuals with normal VA. Further characterization may provide novel insight into future preventive strategies against cardiovascular disease.

The association of chest computed tomography-defined visual emphysema and prognosis in patients with nonsmall cell lung cancer.

Background: Although computed tomography (CT)-defined emphysema is considered a predictor of lung cancer risk, it is not fully clear whether CT-defined emphysema is associated with the prognosis of lung cancer. We aimed to assess the clinical impact of CT-defined emphysema on the survival of lung cancer. Methods: In the prospective cohort study of nonsmall cell lung cancer (NSCLC), the correlation between CT-defined emphysema and clinical variables was analysed. A multivariable Cox regression model was built to assess the association between CT-defined emphysema and overall survival (OS) for up to 8.8 years. The differences in survival analyses were derived by Kaplan-Meier analysis and log-rank testing. Low attenuation area (LAA%) was defined as the per cent of voxels below -950 HU. Results: 854 patients were included and CT-defined emphysema was present in 300 (35.1%) at diagnosis. Epidermal growth factor receptor (EGFR) wild-type (OR 1.998; p<0.001) and anaplastic lymphoma kinase (ALK) wild-type (OR 2.277; p=0.004) were associated with CT-defined emphysema. CT-defined emphysema remained a significant predictor of prognosis adjusting for age, sex, smoking history, tumour histology and Eastern Cooperative Oncology Group Performance Status (ECOG PS), whether in I-IIIA stage (adjusted hazard ratio (HR) 1.745; p=0.017) or in IIIB-IV stage (adjusted HR 1.291; p=0.022). Stratified analyses showed that OS rate among the driver oncogene groups with different CT-defined emphysema status differed significantly (log-rank p<0.001). Furthermore, patients with centrilobular emphysema (CLE) with LAA% >17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; p=0.020). Conclusions: CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.

Double trouble: The interaction of PM2.5 and O3 on respiratory hospital admissions.

The co-occurrence of fine particulate matter (PM2.5) and ozone (O3) pollution during the warm season has become a growing public health concern. The interaction between PM2.5 and O3 and its contribution to disease burden associated with co-pollution has not been thoroughly examined. We collected data on hospital admissions for respiratory diseases from a city-wide hospital discharge database in Beijing between 2013 and 2019. City-wide 24-h mean PM2.5 and daily maximum 8-h mean O3 were averaged from 35 monitoring stations across Beijing. Conditional Poisson regression was employed to estimate the interaction between warm-season PM2.5 and O3 on respiratory admissions. A model incorporating a tensor product term was used to fit the non-linear interaction and estimate the number of respiratory admissions attributable to PM2.5 and O3 pollution. From January 18, 2013 to December 31, 2019, 1,191,308 respiratory admissions were recorded. We observed multiplicative interactions between warm-season PM2.5 and O3 on upper respiratory infections (P = 0.004), pneumonia (P = 0.002), chronic obstructive pulmonary disease (P = 0.041), and total respiratory disease (P < 0.001). PM2.5-O3 co-pollution during warm season exhibited a super-additive effect on respiratory admissions, with a relative excess risk due to interaction of 1.65% (95%CI: 0.46%-2.84%). There was a non-linear pattern of the synergistic effect between PM2.5 and O3 on respiratory admissions. Based on the World Health Organization global air quality guidelines, 12,421 respiratory admissions would be reduced if both daily PM2.5 and O3 concentrations had not exceeded the target (PM2.5 15 µg/m3, O3 100 µg/m3). The number of respiratory admissions attributable to either PM2.5 or O3 pollution decreased by 48.7% from 2013 to 2019. Prioritizing O3 control during the warm season is a cost-effective strategy for Beijing. These findings underscore the significance of concurrently addressing both PM2.5 pollution and O3 pollution during the warm season to alleviate the burden of respiratory diseases.

Urinary ketone bodies and stroke recurrence in patient with acute ischemic stroke or TIA.

BACKGROUND: Urine ketone bodies may appear in different states in the acute stage of stroke. We aimed to examine the association between urine ketone bodies and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in this study. METHODS: In Third China National Stroke Registry (CNSR-III), 14,015 patients with AIS or TIA were screened for urine ketone bodies. The outcomes were any stroke, ischemic stroke and combined vascular events within 1 year. The association of urine ketone bodies with recurrent stroke were analyzed by Cox proportional hazards. RESULTS: During 1 year of follow-up, 1,335 (9.53%) participants experienced recurrent stroke. After adjustment for conventional confounding factors, patients with urine ketone bodies test positive had a higher risk of recurrent stroke (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.13-1.82), compared to those were negative. The correlation between positive urine ketone bodies and recurrent stroke were consistent in patient with (HR, 1.45; 95% CI, 1.00-2.12) and without (HR, 1.40; 95% CI, 1.02-1.94) diabetes. No significant interaction between urine ketone bodies and diabetes were observed. CONCLUSIONS: Positive ketone bodies in urine was independently associated with recurrent stroke in patients with AIS or TIA.

Apolipoprotein Particle and Cardiovascular Risk Prediction (from a Prospective Cohort Study).

The present study aimed to examine the association between discordant apolipoprotein B (Apo B) with low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) and cardiovascular disease (CVD) risk in the Chinese population and to determine whether adding information on Apo B to LDL-C and HDL-C improves CVD risk prediction. This study collected data from the China Health and Nutrition Survey from 2009 to 2015. Discordant Apo B with LDL-C and non-HDL-C were defined based on residual differences and medians. Logistic regression was used to examine the association between discordant Apo B with LDL-C or non-HDL-C and CVD risk. Areas under the receiver operating characteristic curve and categorical net reclassification improvement were utilized to assess the incremental predictive value of Apo B levels for CVD risk. A total of 7,117 participants were included, the mean age was 50.8 ± 14.3 years, 53.6% were female. During the 6-year follow-up, 207 CVD cases were identified. Participants with discordant high Apo B relative to LDL-C or non-HDL-C were at higher risk of CVD than those with the concordant group (odds ratio 1.38, 95% confidence interval 1.01 to 1.87; odds ratio 1.40, 95% confidence interval 1.01 to 1.94, respectively). However, Apo B had no significant contribution to the predictive value of the China atherosclerotic CVD (ASCVD) risk score (areas under the receiver operating characteristic curve 0.788 for China ASCVD score alone vs 0.790 for China ASCVD score plus Apo B). In conclusion, Apo B has the strongest association with CVD risk in healthy Chinese participants than LDL-C and non-HDL-C. However, it has minimal value in CVD risk assessment and discrimination.

Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts arterial stiffness progression.

BACKGROUND: Cross-sectional studies have shown that remnant cholesterol (RC) was associated with arterial stiffness. The present study evaluated the association of RC and the discordance between RC and low-density lipoprotein cholesterol (LDL-C) with arterial stiffness progression. METHODS: Data were derived from the Kailuan study. RC was calculated as total cholesterol - high-density lipoprotein cholesterol - LDL-C. Discordant RC with LDL-C were defined by residuals, cutoff points, and median values. Arterial stiffness progression was assessed by the brachial-ankle pulse wave velocity (baPWV) change, baPWV change rate, and increase/persistently high baPWV. Multivariable linear regression models and logistic regression models were used to explore the association of RC and discordant RC versus LDL-C with the arterial stiffness progression. RESULTS: A total of 10,507 participants were enrolled in this study, with the mean age of 50.8 ± 11.8 years, 60.9% (6,396) of male. Multivariable regression analyses showed that, each 1 mmol/L increase in the RC level was associated with a 12.80 cm/s increase in baPWV change, a 3.08 cm/s/year increase in the baPWV change rate, and 13% (95% CI, 1.05-1.21) of increase in the risk for increase in/persistently high baPWV. Discordant high RC was associated with a 13.65 cm/s increase in baPWV change and 19% (95% CI, 1.06-1.33) of increase in the risk for increase in/persistently high baPWV compared to those with concordant group. CONCLUSION: Discordantly high RC with LDL-C was associated with an increased risk of arterial stiffness progression. The findings demonstrated that RC may be an important marker of future coronary artery disease risk.

Detailed phenotype of RNF213 p.R4810K variant identified by the Chinese patients with acute ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: The ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers. METHODS: We analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%-99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes. RESULTS: A total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year. CONCLUSIONS: The RNF213 p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.

The effects of timing onset and progression of AKI on the clinical outcomes in AKI patients with sepsis: a prospective multicenter cohort study.

BACKGROUND: Limited studies are available concerning on the earlier identification of AKI with sepsis. The aim of the study was to identify the risk factors of AKI early which depended on the timing onset and progression of AKI and investigate the effects of timing onset and progression of AKI on clinical outcomes. METHODS: Patients who developed sepsis during their first 48-h admission to ICU were included. The primary outcome was major adverse kidney events (MAKE) consisted of all-cause mortality, RRT-dependence, or an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. We determined MAKE and in-hospital mortality by multivariable logistic regression and explored the risk factors of early persistent-AKI. C statistics were used to evaluate model fit. RESULTS: 58.7% sepsis patients developed AKI. According to the timing onset and progression of AKI, Early transient-AKI, early persistent-AKI, late transient-AKI, late persistent-AKI were identified. Clinical outcomes were quite different among subgroups. Early persistent-AKI had 3.0-fold (OR 3.04, 95% CI 1.61 - 4.62) risk of MAKE and 2.6-fold (OR 2.60, 95%CI 1.72 - 3.76) risk of in-hospital mortality increased compared with the late transients-AKI. Older age, underweight, obese, faster heart rate, lower MAP, platelet, hematocrit, pH and energy intake during the first 24 h on ICU admission could well predict the early persistent-AKI in patients with sepsis. CONCLUSION: Four AKI subphenotypes were identified based on the timing onset and progression of AKI. Early persistent-AKI showed higher risk of major adverse kidney events and in-hospital mortality. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry (www.chictr.org/cn) under registration number ChiCTR-ECH-13003934.

Evaluation of an innovative mHealth-based integrated modality for smoking cessation in Chinese smokers: protocol for a randomized controlled trial.

BACKGROUND AND AIMS: Developing accessible, affordable, and effective approaches to smoking cessation is crucial for tobacco control. Mobile health (mHealth) based interventions have the potential to aid smokers in quitting, and integrating treatments from multiple sources may further enhance their accessibility and effectiveness. As part of our efforts in smoking cessation, we developed a novel behavioral intervention delivery modality for smoking cessation that integrated three interventions using the WeChat app, called the "Way to Quit" modality (WQ modality). It is presented here the protocol for a randomized controlled trial evaluating the effectiveness, feasibility, and cost-effectiveness of the WQ modality in Chinese smokers. METHODS: Eligible participants (n = 460) will be recruited via online advertisement in Beijing, China. They will be randomly assigned to receive either quitline-based treatment (QT, n = 230) or WQ modality-based treatment (WQ, n = 230) using a block randomization method. Participants in the QT group will receive telephone-assisted treatment over a four-week period (multi-call quitline protocol), while those in the WQ group will receive integrated interventions based on the WQ modality for four weeks. A four-week supply of nicotine replacement therapy (gums) will be provided to all participants. Participants will be asked to complete phone or online follow-up at 1, 3, 6, and 12-months. At 1-month follow-up, individuals with self-reported smoking abstinence for more than 7 days will be invited to receive an exhaled carbon monoxide (CO) test for biochemical validation. The primary aim is to determine whether the WQ modality is effective in assisting smokers in quitting smoking. The secondary aims are to evaluate the acceptability, satisfaction, and cost-effectiveness of the WQ modality. DISCUSSION: If the WQ modality is determined to be effective, acceptable, and affordable, it will be relatively easy to reach and provide professional cessation treatments to the communities, thus helping to reduce the disparities in smoking cessation services between different regions and socioeconomic groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200066427, Registered December 5, 2022.

Development and validation of risk prediction models for new-onset type 2 diabetes in adults with impaired fasting glucose.

AIMS: To develop and validate sex-specific risk prediction models based on easily obtainable clinical data for predicting 5-year risk of type 2 diabetes (T2D) among individuals with impaired fasting glucose (IFG), and generate practical tools for public use. METHODS: The data used for model training and internal validation came from a large prospective cohort (N = 18,384). Two independent cohorts were used for external validation. A two-step approach was applied to screen variables. Coefficient-based models were constructed by multivariate Cox regression analyses, and score-based models were subsequently generated. The predictive power was evaluated by the area under the curve (AUC). RESULTS: During a median follow-up of 7.55 years, 5697 new-onset T2D cases were identified. Predictor variables included age, body mass index, waist circumference, diastolic blood pressure, triglycerides, fasting plasma glucose, and fatty liver. The proposed models outperformed five existing models. In internal validation, the AUCs of the coefficient-based models were 0.741 (95% CI 0.723-0.760) for men and 0.762 (95% CI 0.720-0.802) for women. External validation yielded comparable prediction performance. We finally constructed a risk scoring system and a web calculator. CONCLUSIONS: The risk prediction models and derived tools had well-validated performance to predict the 5-year risk of T2D in IFG adults.

Association of serum albumin to globulin ratio with outcomes in acute ischemic stroke.

BACKGROUND: Serum albumin to globulin ratio (A/G) has been widely used as a representative biomarker for assessing inflammation and nutrition status. However, in patients with acute ischemic stroke (AIS), the predictive value of serum A/G has rarely been reported. We aimed to evaluate whether serum A/G is associated with prognosis in stroke. METHODS: We analyzed data from the Third China National Stroke Registry. The patients were categorized into quartile groups according to the serum A/G at admission. Clinical outcomes included poor functional outcomes (modified Rankin Scale [mRS] score of 3-6 or 2-6) and all-cause mortality at 3 months and1 year. Multivariable logistic regressions and Cox proportional hazards regressions were used to evaluate the association of serum A/G with the risk of poor functional outcomes and all-cause mortality. RESULTS: A total of 11, 298 patients were included in this study. After adjustment for confounding factors, patients in the highest serum A/G quartile had a lower proportion of mRS score 2-6 (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.76-1.00) and mRS score 3-6 (OR, 0.87; 95% CI, 0.73-1.03) at 3 months follow-up. At 1 year follow-up, there was a significant association between higher serum A/G and mRS score 3-6 (OR, 0.68; 95% CI, 0.57-0.81). We also found that the highest serum A/G was related to decreased risk of all-cause mortality (hazard ratio [HR], 0.58; 95% CI, 0.36-0.94) at 3 months follow-up. Similar results were found at 1-year follow-up. CONCLUSIONS: Lower serum A/G levels were associated with poor functional outcomes and all-cause mortality at 3 months and 1-year follow-up in patients with acute ischemic stroke.

Post-Load Insulin Secretion Patterns are Associated with Glycemic Status and Diabetic Complications in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: To examine whether the different patterns of post-load insulin secretion can identify the heterogeneity of type 2 diabetes mellitus (T2DM). METHODS: Six hundred twenty-five inpatients with T2DM at Jining No. 1 People's Hospital were recruited from January 2019 to October 2021. The 140 g steamed bread meal test (SBMT) was conducted on patients with T2DM, and glucose, insulin, and C-peptide levels were recorded at 0, 60, 120, and 180 min. To avoid the effect of exogenous insulin, patients were categorized into three different classes by latent class trajectory analysis based on the post-load secretion patterns of C-peptide. The difference in short- and long-term glycemic status and prevalence of complications distributed among the three classes were compared by multiple linear regression and multiple logistic regression, respectively. RESULTS: There were significant differences in long-term glycemic status (e. g., HbA1c) and short-term glycemic status (e. g., mean blood glucose, time in range) among the three classes. The difference in short-term glycemic status was similar in terms of the whole day, daytime, and nighttime. The prevalence of severe diabetic retinopathy and atherosclerosis showed a decreasing trend among the three classes. CONCLUSIONS: The post-load insulin secretion patterns could well identify the heterogeneity of patients with T2DM in short- and long-term glycemic status and prevalence of complications, providing recommendations for the timely adjustment in treatment regimes of patients with T2DM and promotion of personalized treatment.

Association between residual islet beta-cell function and achieving the target of time in range in inpatients with type 2 diabetes undergoing antidiabetic treatment: An observation study.

AIM: To assess whether the beta-cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. MATERIALS AND METHODS: This cross-sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta-cell function was assessed by the insulin secretion-sensitivity index-2 (ISSI2). RESULTS: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19-8.06) and TAR (OR = 3.40, 95% CI: 1.35-8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90-9.36, P = .07; TAR, OR = 3.14, 95% CI: 1.01-9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91-8.81, P = .07; TAR, OR = 3.24, 95% CI: 1.08-9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66-0.80) and 0.71 (95% CI: 0.63-0.79), respectively. CONCLUSIONS: Beta-cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta-cell function on glycaemic control.

Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile.

BACKGROUND AND OBJECTIVE: Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile. METHODS: Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively). RESULTS: A total of 6,412 CYP2C19 LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48-0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73-1.29), compared with clopidogrel aspirin (p = 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p = 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p < 0.01 for interaction). Analysis in the per-protocol population yielded similar results. DISCUSSION: This post hoc analysis of CHANCE-2 trial showed that CYP2C19 LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. TRIAL REGISTRATION INFORMATION: URL: www. CLINICALTRIALS: gov. Unique identifier: NCT04078737.

Low serum magnesium is associated with poor functional outcome in acute ischemic stroke or transient ischemic attack patients.

AIM: The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all-cause mortality and poor functional outcome. METHODS: We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all-cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2-6/3-6) to examine the relationships. RESULTS: Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80-0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3-6/2-6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04-1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age- and sex-adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02-1.93) for all-cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71-1.50) after adjusting for potential variables. CONCLUSIONS: Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA.

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels. METHODS: This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function. RESULTS: After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053-0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was "paradoxically" associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = - 0.043, 95%CI - 0.067 to - 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%. CONCLUSIONS: In early stage of diabetes, a slightly elevated SBP (140-150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.