Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD. METHODS: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies. Outcomes were SBI (primary) and individual CSVD subtypes. Summary prevalence (95% confidence intervals [CIs]) were obtained using random-effects meta-analysis. Pooled prevalence ratios (PRs) (95% CI) were calculated to compare those with heart disease with available control participants without heart disease from studies. RESULTS: A total of 221 observational studies were included. In those with AF, the prevalence was 36% (31%-41%) for SBI (70 studies, N = 13,589), 25% (19%-31%) for lacune (26 studies, N = 7,172), 62% (49%-74%) for white matter hyperintensity/hypoattenuation (WMH) (34 studies, N = 7,229), and 27% (24%-30%) for microbleed (44 studies, N = 13,654). Stratification by studies where participants with recent stroke were recruited identified no differences in the prevalence of SBI across subgroups (phomogeneity = 0.495). Results were comparable across participants with different heart diseases except for those with PFO, in whom there was a lower prevalence of SBI [21% (13%-30%), 11 studies, N = 1,053] and CSVD. Meta-regressions after pooling those with any heart disease identified associations of increased (study level) age and hypertensives with more SBIs and WMH (pregression <0.05). There was no evidence of a difference in the prevalence of microbleed between those with and without heart disease (PR [95% CI] 1.1 [0.7-1.7]), but a difference was seen in the prevalence of SBI and WMH (PR [95% CI] 2.3 [1.6-3.1] and 1.7 [1.1-2.6], respectively). DISCUSSION: People with heart disease have a high prevalence of SBI (and CSVD), which is similar in those with vs without recent stroke. More research is required to assess causal links and implications for management. TRIAL REGISTRATION INFORMATION: PROSPERO CRD42022378272 (crd.york.ac.uk/PROSPERO/).

Global, regional, and national temporal trends of diet-related ischemic stroke mortality and disability from 1990 to 2019.

BACKGROUND: Stroke is the second leading cause of death and the third leading cause of disability in the general population worldwide. However, the changing trend of ischemic stroke burden attributable to various dietary risk factors has not been fully revealed and may contribute to a better understanding of stroke epidemiology. AIMS: Our article aimed to evaluate the temporal trend of diet-related ischemic stroke burden to inform future research and policy-making. METHODS: This analysis was based on the data from the Global Burden of Disease (GBD) Study 2019 (spanning years 1990 to 2019), and we used the joinpoint regression to model temporal trends in diet-related ischemic stroke burden across countries and regions of the world during the study period. Six specific dietary factors known to influence stroke risk, including sodium, red meat, fiber, vegetables, whole grains, and fruits, were evaluated in the GBD study to determine their individual and joint impact on ischemic stroke. The changing trend was primarily measured by the average annual percent change (AAPC). Age-standardized rates (ASRs) of mortality and years lived with disability (YLD) per 100,000 population were used to evaluate disease burden. Finally, the socioeconomic background, which was quantified as sociodemographic index (SDI), and its association with diet-related ischemic stroke burden were also explored with the Pearson correlation coefficient. RESULTS: During the study period, the ischemic stroke ASR of mortality attributable to overall dietary risk decreased by an average of 1.6% per year, while the ASR of YLD decreased by an average of 0.2% per year. High sodium diet was still a key driver of diet-related ischemic stroke, accounting for 8.4% and 11.0% of deaths and disabilities, respectively, in 2019. In addition, we found a negative association between temporal evolution of stroke burden and socioeconomic background (r = -0.6603 for mortality and r = -0.4224 for disability, P < 0.001), which suggested that the developing countries with weak social and economic foundation faced greater challenges from the ongoing burden of diet-related strokes compared with developed countries. CONCLUSIONS: Our study found declining trends and revealed the current status of diet-related ischemic stroke mortality and disability. Interdisciplinary countermeasures involving the development of effective food policies, evidence-based guidelines, and public education are needed in the future to combat this global epidemic. DATA ACCESS STATEMENT: The data used for analysis were open-access and can be obtained from https://vizhub.healthdata.org/gbd-results/.

Intensive blood pressure lowering and renal function in ischemic stroke patients: secondary analysis of ENCHANTED trial.

BACKGROUND: Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is early change in renal function, defined by a difference in estimated glomerular filtration rate (∆eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation [SD]) and magnitude of reduction within 24 h. RESULTS: Of 2151 participants (mean age 66.9 years; 38% female) included with available baseline eGFR, there were significant differences in attained 144.3±10.2 vs 149.8±12.0 [5.5 mm Hg]; P<0.0001), variation (15.1±5.4 vs 14.0±5.6 mm Hg; P<0.0001) and magnitude of reduction (44.6±16.2 vs 38.7±17.6 mm Hg; P<0.0001) in SBP within 24 hours. 1718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in ∆eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; P=0.29) between the intensive and guideline groups, respectively. The neutral effect on ∆eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputation for missing follow-up eGFR. SBP variability was significantly associated with decreasing ∆eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95%CI -2.43 to -0.28; P for trend=0.01). CONCLUSIONS: Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR. CLINICAL TRIAL REGISTRATION: ENCHANTED is registered at ClinicalTrials.gov (NCT01422616).

Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies.

BACKGROUND: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown. METHODS: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database. RESULTS: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database. CONCLUSIONS: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079.

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke.

BACKGROUND: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. METHODS: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. RESULTS: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). CONCLUSION: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.

Prognostic significance of plasma SDF-1 in acute ischemic stroke patients with diabetes mellitus: the CATIS trial.

BACKGROUND AND OBJECTIVES: Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). METHODS: Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. RESULTS: Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log-SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18-2.32) for recurrent stroke and 1.47 (1.08-1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96-1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. CONCLUSIONS: Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Prognostic significance of serum globulin in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. METHODS: A total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. CONCLUSIONS: A high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.

Prognostic Value of Red Blood Cell Distribution Width and Hemoglobin in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between baseline red blood cell distribution width (RDW) and hemoglobin levels and outcomes after acute intracerebral hemorrhage (ICH) is not well studied. We aimed to investigate the association between baseline RDW and hemoglobin levels with early hematoma expansion (HE) and mortality at 3 months and 1 year in acute ICH patients. METHODS: A total of 393 ICH patients from January 2014 to February 2019 were included. Patients were divided into four groups based on quartiles of RDW and hemoglobin levels at admission, respectively. Logistic regression models were used to estimate the effect of the levels of RDW and hemoglobin on early HE (absolute hematoma growth >6 mL from baseline to follow-up) and allcaused mortality at 3 months and 1 year. RESULTS: There were no significant associations between baseline RDW and hemoglobin levels and early HE. The 3-month mortality (adjusted odds ratio [OR] 2.88; 95% confidence intervals [CI] 0.96-8.64) and 1-year mortality (adjusted OR 3.16, 95% CI 1.08-9.21) was significantly higher in patients with the highest RDW level (Q4) compared to those with the lowest RDW level (Q1). Moreover, patients with the lowest hemoglobin level were significantly associated with increased odds of all-cause mortality at 3-month (adjusted OR 3.95, 95% CI 1.26-12.4) and 1-year (adjusted OR 4.42, 95% CI 1.56-12.5) compared to those with highest hemoglobin level. CONCLUSION: In patients with acute ICH, a higher level of RDW at admission significantly increased the risk of all-cause mortality at 1 year. Moreover, a decreased hemoglobin level at admission was also associated with a higher risk of all-cause mortality at 3 months and 1 year.

Multidrug-Resistant Organism Infections of Inpatients in a Hospital in Eastern China from 2015 to 2021.

Background: The prevalence of multidrug-resistant organisms (MDRO) is gradually increasing in the global scope, causing serious burden to patients and society, which is an important public health problem. Objective: To analyze the distribution and trend of MDROs and provide a reference for hospital infection control. Methods: Collected data on MDROs infections among inpatients in a Grade III Level A hospital in Suzhou from 2015 to 2021, including drug-resistant bacteria strains and specimen sources, etc. Mantel-Haenszel χ2 test was used to evaluate the trend of infection rates over the years and SPSS version 26.0 was used for statistics analysis. Results: The hospital infection rate showed an overall downward trend across the seven-year period, ranging from 1.53% to 2.10%. According to the analysis of change of drug-resistant bacteria strains, the highest infection rate was carbapenem-resistant Acinetobacter baumannii (CRABA) (63.74%), followed by methicillin-resistant Staphylococcus aureus (MRSA) (46.37%), carbapenem-resistant Pseudomonas aeruginosa (CRPAE) (24.87%), carbapenem-resistant Enterobacteriaceae (CRE) (13.14%) and vancomycin-resistant Enterococcus (VRE) (0.42%). The results of Mantel-Haenszel χ2 test showed that there was a linear relationship between the detection rate of CRE and CRPAE and the time (P<0.001), but the correlation was not strong (R = 0.136; R = 0.139). The overall detection rate of the five pathogens also increased (P<0.001). The majority of the specimens, mainly from sputum, airway secretions, and midstream urine, had a detection rate of over 70%. Conclusion: Our data showed that the detection rate of MDROs generally increased from 2015 to 2021, although the hospital infection rate displayed a declining trend. Among the detection rate MDROs, the highest was CRABA, and the lowest was VRE. It is necessary to enhance the prevention, control, and management of MDROs infections in the clinical practice.

The association between serum phosphorus and common carotid artery intima-media thickness in ischemic stroke patients.

Purpose: An elevated concentration of phosphorus is associated with an increased risk of atherosclerosis and cardiovascular diseases. Common carotid artery intima-media thickness (cIMT) is an imaging marker of atherosclerosis. However, data on the relationship between phosphorus and cIMT in ischemic stroke are scarce. We aimed to evaluate the association between serum phosphorus levels and cIMT in patients who had experienced ischemic stroke. Patients and methods: A total of 1,450 ischemic stroke patients were enrolled. Participants were divided into four groups (quartiles) according to baseline serum phosphorus level. Carotid atherosclerosis was identified by measurement of cIMT; abnormal cIMT was defined as a maximum cIMT or mean cIMT ≥ 1 mm. Multivariable logistic regression models were used to assess the association between serum phosphorus level and the presence of abnormal cIMT. Results: In the multivariable adjusted analysis, falling into the highest quartile for serum phosphorus (Q4) was associated with a 2.00-fold increased risk of having abnormal maximum cIMT [adjusted odds ratio (OR) 2.00; 95% confidence interval (CI) 1.44-2.79] and a 1.76-fold increased risk of having abnormal mean cIMT (adjusted OR 1.76; 95% CI 1.22-2.53) in comparison to Q1. Furthermore, the association between serum phosphorus and abnormal cIMT was confirmed in analyses treating serum phosphorus as a continuous variable and in subgroup analyses. Conclusion: In acute ischemic stroke patients, baseline elevated serum phosphorus level was found to be independently associated with carotid atherosclerosis, as measured by cIMT.

The prognostic value of deep earlobe creases in patients with acute ischemic stroke.

Background and purpose: Data on earlobe crease (ELC) among patients with acute ischemic stroke (AIS) are limited. Here, we determined the frequency and characteristics of ELC and the prognostic effect of ELC among AIS patients. Methods: A total of 936 patients with acute AIS were enrolled during the period between December 2018 and December 2019. The patients were divided into those without and with ELC, unilateral and bilateral ELC, and shallow and deep ELC, according to the photographs taken of the bilateral ears. Logistic regression models were used to estimate the effect of ELC, bilateral ELC, and deep ELC on poor functional outcomes at 90 days (a modified Rankin Scale score ≥2) in AIS patients. Results: Among the 936 AIS patients, there were 746 (79.7%) patients with ELC. Among patients with ELC, there were 156 (20.9%) patients with unilateral ELC and 590 (79.1%) with bilateral ELC and 476 (63.8%) patients with shallow ELC and 270 (36.2%) with deep ELC. After adjusting for age, sex, baseline NIHSS score, and other potential covariates, patients with deep ELC were associated with a 1.87-fold [odds ratio (OR) 1.87; 95% confidence interval (CI), 1.13-3.09] and 1.63-fold (OR 1.63; 95%CI, 1.14-2.34) increase in the risk of poor functional outcome at 90 days in comparison with those without ELC or shallow ELC. Conclusion: ELC was a common phenomenon, and eight out of ten AIS patients had ELC. Most patients had bilateral ELC, and more than one-third had deep ELC. Deep ELC was independently associated with an increased risk of poor functional outcome at 90 days.

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis.

BACKGROUND: The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood. METHODS: Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months. RESULTS: The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874). CONCLUSIONS: AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients.

BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Eosinophil: A New Circulating Biomarker for Risk of Poor Outcome in Stroke Patients Undergoing Mechanical Thrombectomy.

Objective: Acute ischemic stroke (AIS), caused by occlusion of large vessel, is a serious life-threatening disease. This study aimed to comprehensively investigate the association of 14 common and readily available circulating biomarkers with the 90-day modified Rankin Scale (mRS) score in patients undergoing mechanical thrombectomy (MT). Methods: This study included patients with anterior circulation large vessel occlusive stroke treated with MT from 05/2017 to 12/2021. Baseline comparisons of poor outcome were performed among enrolled patients. Factors that may be associated with the mRS score were assessed using correlation analysis. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of circulating biomarkers and poor outcome. Results: The mRS score has a strong correlation with neutrophil to lymphocyte ratio (NLR) and eosinophil levels (all rs>0.4 in absolute value and all P<0.001) in addition to a high correlation with National Institute of Health Stroke Scale (NIHSS) score (rs=0.40, P<0.001). There was also a high correlation between NLR and eosinophil (rs=-0.58, P<0.001). In the multivariate regression analysis, only neutrophil (adjusted OR=1.301, 95% CI: 1.155-1.465, P<0.001), eosinophil (adjusted OR<0.001, 95% CI: <0.001-0.016, P<0.001), and NLR (adjusted OR=1.158, 95% CI: 1.082-1.241, P<0.001) were independently associated with poor outcome. Conclusion: This study evaluated a series of circulating biomarkers and found that neutrophil, eosinophil, and NLR independently predicted poor outcome after MT in AIS patients. There was a significant negative correlation between eosinophil and NLR levels.

Baseline brain imaging signs in patients with ischaemic stroke by the presence of atrial fibrillation: the ENCHANTED trial.

BACKGROUND: We aimed to assess the association of atrial fibrillation (AF) on outcomes in a post hoc analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) and how this association is modified by baseline imaging features. METHODS: Inverse probability of treatment weight was used to remove baseline imbalances between those with and without AF. The primary outcome was the modified Rankin Scale (mRS) scores at 90 days. Secondary outcomes were symptomatic intracerebral haemorrhage (sICH), early neurological deterioration or death within 24 h, and death at 90 days. The logistic regression model was used to determine the associations. RESULTS: Of the 3285 patients included in this analysis, 636 (19%) had AF at baseline. Compared with non-AF, AF was not significantly associated with an unfavourable shift of mRS (odds ratio 1.09; 95% confidence interval, 0.96-1.24), but with sICH (2.82; 1.78-4.48; IST-3 criteria), early neurological deterioration or death within 24 h (1.31; 1.01-1.70), and death (1.42; 1.12-1.79). Among patients with acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions), AF was associated with the increased risk of all the poor outcomes (all P < 0.04 for interaction). CONCLUSIONS: We found AF increased risk of sICH, early neurological deterioration or death and death, but not unfavourable functional recovery at day 90 after thrombolysis in patients with AIS. The presence of acute ischaemic brain imaging signs at stroke presentation could be used to improve risk stratification in the presence of AF. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01422616).

Prognostic significance of blood pressure parameters after mechanical thrombectomy according to collateral status.

BACKGROUND: Mechanical thrombectomy (MT) has been proven as an effective and safe therapy for patients with acute ischemic stroke from large vessel occlusion. However, there is still a controversial topic about post-procedural management including blood pressure (BP). METHODS: A total of 294 patients who received MT in Second Affiliated Hospital of Soochow University from April 2017 to September 2021 were included consecutively. The association of blood pressure parameters (BPV and hypotension time) with poor functional outcome was evaluated using logistic regression models. Meanwhile, the effects of BP parameters on mortality was analyzed using cox proportional hazards regression models. Furthermore, the corresponding multiplicative term was added to the above models to study the interaction between BP parameters and CS. RESULTS: Two hundred ninety four patients were included finally. The mean age was 65.5 years. At the 3-month follow-up, 187(61.5%) had poor functional outcome and 70(23.0%) died. Regardless of the CS, BP CV is positively associated with poor outcome. Hypotension time was negatively associated with poor outcome. We conducted a subgroup analysis according to CS. BPV was significantly associated with mortality at 3-month and displayed a trend toward poor outcome for patients with poor CS only. The interaction between SBP CV and CS with respect to mortality after adjusting for confounding factors was statistically significant (P for interaction = 0.025) and the interaction between MAP CV and CS with respect to mortality after multivariate adjustment was also statistically significant (P for interaction = 0.005). CONCLUSION: In MT-treated stroke patients, higher BPV in the first 72 h is significantly associated with poor functional outcome and mortality at 3-month regardless of CS. This association was also found for hypotension time. Further analysis showed CS modified the association between BPV and clinical prognosis. BPV displayed a trend toward poor outcome for patients with poor CS.

Effects of Different Etiologies of Anterior Circulation Tandem Lesions on Short-term Prognosis of Acute Ischemic Stroke.

INTRODUCTION: The prognosis of anterior circulation tandem lesions caused by carotid artery dissection (CAD) and large artery atherosclerosis (LAA) after mechanical thrombectomy is controversial. By analyzing the clinical data of different etiologies, we explored the best treatment plan. METHODS: Clinical data of patients with anterior circulation tandem lesions admitted to the Second Affiliated Hospital of Soochow University from April 2018 to October 2021 were retrospectively collected. The Modified Rankin Scale was used as the standard to evaluate the functional prognosis of patients at 3 months. Safety assessment included symptomatic intracranial hemorrhage (sICH) and mortality. The technical evaluation of interventional procedures included operation time, successful recanalization, and times of pass. RESULTS: 74 patients were enrolled, 59 in the LAA group and 15 in the CAD group. The two groups were similar regarding the proportion of successful recanalization, the bridge treatment and the choice of surgical instruments. The puncture to recanalization time and the onset of symptoms to successful recanalization time had no significant difference (p > 0.05). There were no significant differences in hemorrhage transformation (p = 0.26), sICH (p > 0.999), good functional prognosis (p = 0.054), and mortality (p = 0.181) between the two groups. We found a trend toward a better functional outcome at 3 months in the CAD group (p = 0.054). CONCLUSION: The tandem lesions of anterior circulation caused by CAD tend to have a good functional prognosis in 3 months. The proportion of successful recanalization and surgical safety was similar between the two groups.

Triglyceride-glucose index and short-term functional outcome and in-hospital mortality in patients with ischemic stroke.

BACKGROUND AND AIMS: The triglyceride-glucose (TyG) index has been demonstrated as an independent marker of ischemic stroke. Whether TyG index predicts short-term outcomes in patients with ischemic stroke remains uncertain. The aim of the study was to investigate the early prognosis value of TyG index in ischemic stroke patients. METHODS AND RESULTS: A total of 3216 acute ischemic stroke patients from 22 hospitals were included in this analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Logistic regression model was performed to estimate the relationship between TyG index and unfavorable functional outcome of death or disability (modified Rankin Scale score of 4-6) at discharge. Risk reclassification with TyG index to predict unfavorable functional outcome was analyzed. During hospitalization, 748 patients (23.3%) experienced poor functional outcome and 105 patients (3.3%) died from all causes. The multivariable adjusted odds ratios for the highest versus lowest quartile of TyG index was 1.62 (95% CI 1.15-2.29) for unfavorable functional outcome at discharge. The addition of TyG index to the conventional model improved the risk reclassification (net reclassification improvement 10.37%; integrated discrimination improvement 0.27%; both p < 0.05) for poor functional outcome. Moreover, TyG index was associated with an odds ratio (95% CI) of 1.26 (1.02-1.55) for an ordinal shift in mRS score and 2.49 (1.21-5.12) for in-hospital mortality. CONCLUSIONS: Higher TyG index was associated with higher risk of unfavorable functional outcome at discharge and in-hospital mortality, implicating the significant short-term prognostic effect of TyG index in patients with ischemic stroke.

Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke.

BACKGROUND: DPP4 (dipeptidyl peptidase-4) inhibitors have been proven to promote neuronal regeneration, reverse the development of cognitive deficits. However, the association of circulating soluble form (sDPP4 [soluble DPP4]) with poststroke cognitive impairment (PSCI) is unclear. We aimed to investigate the association between plasma sDPP4 levels and PSCI in patients with ischemic stroke. METHODS: A total of 600 noncardioembolic stroke patients were included based on a preplanned ancillary study from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Montreal Cognitive Assessment to evaluate cognitive function at 3 months follow-up after ischemic stroke. Binary logistic regression analyses were performed to investigate the association of plasma sDPP4 levels with subsequent PSCI. We further calculated integrated discrimination improvement and category-free net reclassification improvement to investigate the incremental prognostic effect of plasma sDPP4 beyond the basic model with conventional risk factors. RESULTS: Plasma sDPP4 was inversely associated with PSCI after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartile of sDPP4 was 0.49 (0.29-0.81; P for trend=0.011). Each 1-SD increase of logarithm-transformed plasma sDPP4 concentration was associated with 17% (odds ratio, 0.83 [95% CI, 0.70-0.99]) lower risk of PSCI. Adding plasma sDPP4 to the basic model notably improved risk reclassification for PSCI, as shown by a category-free net reclassification improvement of 19.10% (95% CI, 2.52%-35.68%; P=0.03) and integrated discrimination improvement of 0.79% (95% CI, 0.13%-1.46%; P=0.02). CONCLUSIONS: Higher plasma sDPP4 levels were associated with decreased risk of cognitive impairment after noncardioembolic ischemic stroke.