Redefining Infarction Size for Small-Vessel Occlusion in Acute Ischemic Stroke: A Retrospective Case-Control Study.

BACKGROUND/OBJECTIVES: Small-vessel occlusion, previously referred to as lacunar infarcts, accounts for approximately one-third of all ischemic strokes, using an axial diameter of less than 20 mm on diffusion-weighted imaging. However, this threshold may not adequately differentiate small-vessel occlusion from other pathologies, such as branch atheromatous disease (BAD) and embolism. This study aimed to assess the clinical significance and pathological implications of acute small subcortical infarctions (SSIs) based on infarct diameter. METHODS: We conducted a retrospective case-control study using data from stroke patients recorded between 2016 and 2021 of the Stroke Registry in Chang Gung Healthcare System. Patients with acute SSIs in penetrating artery territories were included. Key variables such as patient demographics, stroke severity, and medical history were collected. Infarcts were categorized based on size, and the presence of early neurological deterioration (END) and favorable functional outcomes were assessed. RESULTS: Among the 855 patients with acute SSIs, the median age was 70 years and the median National Institutes of Health Stroke Scale (NIHSS) score at arrival was four. END occurred in 97 patients (11.3%). Those who experienced END were significantly less likely to achieve a favorable functional outcome compared to those who did not (18.6% vs. 59.9%, p < 0.001). The incidence of END increased progressively with infarct sizes of 15 mm or larger, with the optimal threshold for predicting END identified as 15.5 mm and for BAD, it was 12.1 mm. A multiple logistic regression analysis revealed that motor tract involvement [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI) 1.1-4.7], an initial heart rate greater than 90 beats per minute (aOR 2.3; 95% CI 1.2-4.3), and a larger infarct size (15 mm to less than 20 mm vs. 10 mm to less than 15 mm; aOR 3.0; 95% CI 1.4-6.3) were significantly associated with END. CONCLUSIONS: Our findings suggest that setting the upper limit for small-vessel occlusion at 15 mm would be more effective in distinguishing it from BAD. However, these findings should be interpreted in the context of the retrospective design and study population. Further multi-center research utilizing high-resolution vessel wall imaging is necessary to refine this threshold and enhance diagnostic accuracy.

Preliminary results on temporal evolution and clinical implications of atherosclerotic plaque in branch atheromatous disease after statin treatment.

Background: Branch atheromatous disease (BAD) is a primary cause of early neurological deterioration (END) in penetrating artery occlusion, leading to poor functional outcomes. While it has been proposed to classify BAD under large artery atherosclerosis, uncertainty exists regarding the optimal treatment strategy, including cholesterol-lowering targets. Objectives: We aimed to assess the clinical implications and temporal changes of atherosclerotic plaques before and after high-intensity statin treatment. Design: This is a high-resolution vessel-wall imaging sub-analysis of the trial of Statin and Dual Antiplatelet Therapy in Preventing Early Neurological Deterioration in Branch Atheromatous Disease (SATBRAD). Methods: In this prospective, single-group cohort study, participants in the treatment arm of the SATBRAD trial received early dual antiplatelet therapy and high-intensity statin treatment. The majority of these participants subsequently underwent high-resolution vessel-wall magnetic resonance imaging (MRI). Those with atheromatous plaques in the parent artery continued high-intensity statin treatment for 6 months, followed by a repeat MRI to monitor plaque changes. Results: There were 57 patients who underwent vessel-wall imaging and 24 exhibited contrast-enhanced plaques. Patients with contrast-enhanced plaques showed higher rates of END (29.2% vs 6.1%, p = 0.027), perfusion defects (62.5% vs 24.2%, p = 0.004), and lower rates of good outcomes at 3 months (50.0% vs 81.8%, p = 0.011). After adjusting for confounding factors, contrast-enhanced plaque had a negative impact on achieving a good outcome at 3 months (adjusted odds ratio = 0.04; 95% confidence interval = <0.01-0.60). Following high-intensity statin treatment in 36 patients, there was a notable reduction in stenosis (33.7% vs 29.3%, p = 0.005) and contrast-enhanced plaque volume (16.3 vs 11.6 mm3, p = 0.015). Conclusion: The study highlighted the association between contrast-enhanced atherosclerotic plaques, END, and poor functional outcomes, with high-intensity treatment leading to plaque volume reduction. These results underscore the shared pathology between BAD and intracranial atherosclerosis, emphasizing the necessity for further research and tailored treatment strategies for BAD. Trial registration: ClinicalTrials.gov; Identifier: NCT04824911 (https://clinicaltrials.gov/study/NCT04824911).

Changes in atherosclerosis and its impact on health after statin treatment: what we learned from detailed vessel imaging in the SATBRAD trial Branch atheromatous disease (BAD) is a major cause of early worsening of stroke symptoms, leading to poor recovery. While some experts believe BAD should be treated like large artery disease, the best treatment approach, including cholesterol-lowering targets, remains unclear. This study aimed to assess how high-intensity statin treatment affects atherosclerotic plaques over time and its impact on patient health. Analyzing detailed vessel images from the SATBRAD trial, where patients received high-intensity statins and magnetic resonance imaging, revealed that 24 out of 57 patients had plaques that showed up clearly with contrast enhancement. These patients were more likely to experience early worsening of stroke symptoms and perfusion compromise and had poorer outcomes. After six months of high-intensity statin treatment, there was a significant reduction in plaque size and vessel narrowing. The study concluded that contrast-enhanced plaques are linked to worse early stroke symptoms and poor recovery, but high-intensity statin treatment can reduce plaque size, suggesting that BAD may share similarities with larger artery disease and highlighting the need for further research and tailored treatments for BAD.

Enhanced versus standard hydration in acute ischemic stroke: REVIVE-A randomized clinical trial.

RATIONALE: Early neurological deterioration (END) within 72 h of stroke onset is associated with poor prognosis. Optimizing hydration might reduce the risk of END. AIMS: This study aimed to determine in acute ischemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as well as whether it increased the incidence of early neurological improvement (secondary), at 72 h after admission. SAMPLE SIZE ESTIMATE: A total of 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicenter, parallel-group, randomized controlled trial conducted at four hospitals from April 2014 to July 2020, with data analyzed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischemic stroke patients with measurable neurological deficits of onset within 12 h of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ⩾ 15 at point of admission were enrolled and randomized to 0.9% sodium chloride infusions of varying rates-enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 h) versus standard hydration (60 mL/h for 8 h), followed by maintenance infusion of 40-80 mL/h for the subsequent 64 h. The primary outcome measure was the incidence of major END at 72 h after admission, defined as an increase in National Institutes of Health Stroke Scale of ⩾ 4 points from baseline. RESULTS: Overall, 487 participants were randomized (median age 67 years; 287 females). At 72 h, 7 (2.9%) in the enhanced hydration arm and 5 (2.0%) in the standard hydration developed major END (p = 0.54). The incidence of minor END and early neurological improvement did not differ between treatment arms. CONCLUSION AND RELEVANCE: Enhanced hydration did not reduce END or improve short-term outcomes in acute ischemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).

Exploring the relationship between lesion morphology and pathogenesis in acute small subcortical infarction.

Introduction Acute small subcortical infarctions (SSIs) result from occlusions of small penetrating arteries, and the underlying pathological factors can have different clinical implications. The objective of this study was to assess the clinical relevance of acute SSIs based on their sizes and morphologies. Methods This retrospective case-control study analyzed clinical and imaging data of stroke patients with acute SSIs in penetrating artery territories who underwent MRI within 5 days of stroke onset, registered between 2016 and 2020. We categorized these patients into three groups based on size and morphology: diameter < 20mm, diameter ≧ 20mm, and separated lesions. We then evaluated their clinical characteristics and outcomes. Results We analyzed 726 stroke patients with SSIs, among whom 573 had a diameter <20mm, 99 had a diameter ≥20mm, and 54 had separated lesions. The patients had a median age of 70 years and a median National Institutes of Health Stroke Scale (NIHSS) score of 4 on arrival. Patients who experienced early neurological deterioration (END) had a significantly lower chance of good functional outcomes (27.3% vs. 64.4%, p<0.001). Patients with a diameter ≧20mm had the most severe NIHSS on arrival and at day 3, the highest rate of END, and the lowest rate of good outcome at 3 months. The incidence of cardioembolism did not differ between patients with diameters of ≥20mm and <20mm. However, multiple logistic regression analysis revealed that separated lesions were more likely to be associated with cardioembolic stroke (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 2.0-28.5) and parent artery stenosis >50% (aOR, 3.8; 95% CI, 2.1-7.0) than a diameter of <20mm. Moreover, SSIs with a diameter of ≥20mm was found to be associated with an increased risk of END compared to that with a diameter of <20mm (aOR, 2.9; 95% CI, 1.7-5.2). Conclusion Our study suggests that the sizes and morphologies of acute SSIs may indicate different underlying pathologies and be linked to diverse clinical outcomes. Our findings also challenge the current imaging criteria for embolic stroke of undetermined source, as we did not find a link between large subcortical infarction and cardioembolic stroke.

An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration.

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31-22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.

Human thirst behavior requires transformation of sensory inputs by intrinsic brain networks.

BACKGROUND: To survive and thrive, many animals, including humans, have evolved goal-directed behaviors that can respond to specific physiological needs. An example is thirst, where the physiological need to maintain water balance drives the behavioral basic instinct to drink. Determining the neural basis of such behaviors, including thirst response, can provide insights into the way brain-wide systems transform sensory inputs into behavioral outputs. However, the neural basis underlying this spontaneous behavior remains unclear. Here, we provide a model of the neural basis of human thirst behavior. RESULTS: We used fMRI, coupled with functional connectivity analysis and serial-multiple mediation analysis, we found that the physiological need for water is first detected by the median preoptic nucleus (MnPO), which then regulates the intention of drinking via serial large-scale spontaneous thought-related intrinsic network interactions that include the default mode network, salience network, and frontal-parietal control network. CONCLUSIONS: Our study demonstrates that the transformation in humans of sensory inputs for a single physiological need, such as to maintain water balance, requires large-scale intrinsic brain networks to transform this input into a spontaneous human behavioral response.

PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging.

INTRODUCTION: Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin-kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis. METHODS AND ANALYSIS: In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40-80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT05001984; Pre-results.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study.

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

INTRODUCTION: Branch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent stroke in acute small subcortical infarction caused by BAD. METHODS AND ANALYSIS: In this prospective, single-centre, open-label, non-randomised, single-arm study using a historical control, we will compare early DAPT and high-intensity statin treatment with a historical control group of patients with BAD who were treated with single antiplatelet therapy without high-intensity statin treatment. Patients will be eligible for enrolment if they are admitted for acute ischaemic stroke within 24 hours, have a National Institutes of Health Stroke Scale (NIHSS) score of 1-8 and are diagnosed with BAD by MRI. Patients will take aspirin, clopidogrel and high-intensity statins (atorvastatin or rosuvastatin) within 24 hours of stroke onset, followed by aspirin or clopidogrel alone from day 22. The primary endpoint is the percentage of patients who develop END within 7 days of stroke onset (defined as an increase in the NIHSS score ≥2 points) and recurrent stroke within 30 days. The total sample sizes will be 138 for the intervention group and 277 for the control group. A historical control group will be drawn from previous prospective observation studies. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (202001386A3). All participants will have to sign and date an informed consent form. The findings arising from this study will be disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT04824911.

Effects of Early Rehydration on Brain Perfusion and Infarct Core after Middle Cerebral Artery Occlusion in Rats.

Imaging evidence for the effect of rehydration on cerebral perfusion and brain ischemia has never been proposed in the literature. This study aimed to test the hypothesis that early rehydration treatment can improve cerebral perfusion and decrease infarct volume, consequently reducing mortality of dehydrated stroke animals. METHODS: Thirty dehydrated experimental rats were randomly assigned to either a rehydration or control group after middle cerebral artery occlusion (MCAO). Diffusion-weighted imaging and dynamic contrast enhancement perfusion imaging were performed at 30 min and 6 h after MCAO using a 9.4T MR imaging scanner to measure the infarct volume and brain perfusion. RESULTS: The survival rates after the first MRI scan were 91.7% for the rehydration group and 58.3% for the control group (p = 0.059). The survival rates after the second MRI scan were 66.7% for the rehydration group, and 8.3% of the control group survived (p = 0.003). The infarct volume of the rehydration group was significantly smaller than control group at 30 min after MCAO (p = 0.007). The delay time and time to maximum were significantly shorter in the rehydration group at 30 min (p = 0.004 and 0.035, respectively). CONCLUSIONS: The findings suggest that early rehydration therapy can decrease the infarct volume, shorten the delay time of cerebral perfusion, and increase survival of dehydrated ischemic-stroke rats. This preliminary study provided imaging evidence that more intensive early hydration therapies and reperfusion strategies may be necessary for acute stroke patients with dehydrated status.

2020 Guideline for Prehospital Management, Emergency Evaluation and Treatment of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals from the Taiwan Society of Emergency Medicine and Taiwan Stroke Society.

To improve the clinical outcomes of patients with acute ischemic stroke, the public, pre-hospital care system, and hospitals should cooperate to achieve quick assessment and management for such patients and to start treatment as soon as possible. To reach the goal, the Consensus Group, including emergency physicians and neurologists in the Taiwan Society of Emergency Medicine and Taiwan Stroke Society, performed an updated review and discussion for the local guidelines. The guidelines consist of 12 parts, including public education program, evaluation and management in the emergency medical system, emergency medical system, assessment of stroke care capability of the hospital by independent parties, stroke team of the hospital, telemedicine, organization, and multifaceted integration, improvement of quality of care process of stroke system, initial clinical and imaging evaluations after arriving at the hospital, imaging evaluation for indications of intravenous thrombolysis, imaging evaluation for indications of endovascular thrombectomy, and other diagnostics. For detailed contents in Chinese, please refer to the Taiwan Stroke Society Guideline and Taiwan Emergency Medicine Bulletin.

Do initially non-dehydrated patients with acute ischemic stroke need fluid supplement?

Background: We previously found that dehydration is an independent predictor of early deterioration after acute ischemic stroke and rehydration helps to improve outcomes. There is limited evidence of how to treat patients who are initially non-dehydrated. In this study, we tested the hypothesis that rehydration therapy, based on the daily urine specific gravity, will improve the outcome of ischemic stroke patients who are initially non-dehydrated. Methods: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the first 5 days of study group, a daily urine specific gravity of > 1.020 g/ml was taken as indication for rehydration and patients were advised to drink water via oral or tubal feeding with a dose of 5 ml/kg body weight right away and after dinner. Control group patients were rehydrated without reference to urine specific gravity. An increase in National Institutes of Health Stroke Scale score of ≥ 4 within three days was defined as having stroke-in-evolution. Scores of ≤ 1 on the modified Rankin scale at 3 months were considered to indicate a favorable outcome. Results: A total of 125 patients were analyzed, 46 in the study group and 79 in the control group. The groups did not significantly differ in the stroke-in-evolution rate (4.3% vs. 8.2%, P = 0.474). The rate of favorable outcome at 3 months was significantly higher in the study group than in the control group (56.5% vs. 27.8%, P = 0.001). Conclusions: Urine specific gravity-based hydration might be a useful method to improve functional outcomes of patients with acute ischemic stroke who were non-dehydrated at admission.

Massive transfusion in upper gastrointestinal bleeding: a new scoring system.

Background: Massive transfusion in patients with upper gastrointestinal bleeding (UGIB) was not investigated. We developed a new scoring system to predict massive transfusion and to enhance care and early resource mobilization. Methods: Massive transfusion was defined as transfusion with ≥10 units of red blood cells within the first 24 h. Data were extracted from a 10-year, six-hospital database. Logistic regression was applied to derive a risk score for massive transfusion using data from 2006 to 2010, in 24,736 patients (developmental cohort). The score was then validated using data from 2011 to 2015 in 27,449 patients (validation cohort). Area under the receiver operating characteristic (AUROC) curve was performed to assess prediction accuracy. Results: Five characteristics were independently associated (p < .001) with massive transfusion: presence of band-form cells among white blood cells (band form >0), international normalized ratio (INR) >1.5, pulse >100 beats per minute or systolic blood pressure <100 mmHg (shock), haemoglobin <8.0 g/dL and endoscopic therapy. The new scoring system successfully discriminated well between UGIB patients requiring massive transfusion and those who did not in both cohorts (AUROC: 0.831, 95%CI: 0.827-0.836; AUROC: 0.822, 95% CI: 0.817-0.826, respectively). Conclusions: The new scoring system predicts massive transfusion requirement in patients with UGIB well. Key messages Massive transfusion is a life-saving management in massive upper gastrointestinal bleeding. How to identify patients requiring massive transfusion in upper gastrointestinal bleeding is poorly documented. Approximately 3.9% of upper gastrointestinal bleeding patients require massive transfusion. A new scoring system is developed to identify patients requiring massive transfusion with high accuracy.

Effects of Dehydration on Brain Perfusion and Infarct Core After Acute Middle Cerebral Artery Occlusion in Rats: Evidence From High-Field Magnetic Resonance Imaging.

Background: Dehydration is common among ischemic stroke patients and is associated with early neurological deterioration and poor outcome. This study aimed to test the hypothesis that dehydration status is associated with decreased cerebral perfusion and aggravation of ischemic brain injury. Methods: Diffusion-weighted imaging and arterial spin labeling perfusion MR imaging were performed on rats with middle cerebral artery occlusion (MCAO) by using a 9.4T MR imaging scanner to measure the volume of infarction and relative cerebral blood flow (rCBF) after infarction. Twenty-five rats were assigned to either a dehydration group or normal hydration group, and dehydration status was achieved by water deprivation for 48 h prior to MCAO. Results: The volume of the infarction was significantly larger for the dehydration group at the 4th h after MCAO (p = 0.040). The progression in the infarct volume between the 1st and 4th h was also larger in the dehydration group (p = 0.021). The average rCBF values of the contralateral normal hemispheres at the 1st and the 4th h were significantly lower in the dehydration group (p = 0.027 and 0.040, respectively). Conclusions: Our findings suggested that dehydration status is associated with the progression of infarct volume and decreases in cerebral blood flow during the acute stage of ischemic stroke. This preliminary study provided an imaging clue that more intensive hydration therapies and reperfusion strategies are necessary for the management of acute ischemic stroke patients with dehydration status.

Association of Chronic Kidney Disease With Small Vessel Disease in Patients With Hypertensive Intracerebral Hemorrhage.

BACKGROUND: Chronic kidney disease (CKD) has been closely associated with hypertension and stroke. Although studies have reported the relationship between CKD and cerebral small vessel disease (SVD), the link between CKD, hypertension, and SVD is uncertain. The aim of this study was to investigate the association between CKD and SVD in patients with strictly hypertensive intracerebral hemorrhage (ICH). METHODS: 142 patients with acute hypertensive ICH were enrolled in this study. Magnetic resonance imaging was performed to assess imaging markers for SVD. Patients were categorized into three CKD groups based on the degree of kidney dysfunction [glomerular filtration rate (GFR) in milliliters per minute per 1.73 m2]: normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60). RESULTS: The prevalence rate of mild and moderate to severe CKD was 50 and 14.8%, respectively. The stage of CKD was associated with history of chronic hypertension (p = 0.046) as well as the prevalence rate of overall and deep cerebral microbleed (CMB) (p = 0.001 and p = 0.002, respectively). The stage of CKD was a significant risk factor for deep white matter hyperintensity (WMH) (OR 1.848; 95% CI 1.022-3.343, p = 0.042), overall CMB (OR 2.628; 95% CI 1.462-4.724, p = 0.001), lobar CMB (OR 2.106; 95% CI 1.119-3.963, p = 0.021), and deep CMB (OR 2.237; 95% CI 1.263-3.960, p = 0.006), even after adjustment for confounders. CONCLUSION: In patients with hypertensive ICH, the prevalence of CKD is high even at the early stage of renal function impairment and is associated with the prevalence of CMB and deep WMH. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and cerebral SVD.

The association between red blood cell transfusion and outcomes in patients with upper gastrointestinal bleeding.

BACKGROUND: The benefits of transfusion for acute upper gastrointestinal bleeding (UGIB) have not been well established; however, previous studies suggest that transfusion is associated with adverse outcomes. We performed an observational study using a 10-year database to analyze the association between red blood cell (RBC) transfusion and outcomes in patients with UGIB in the emergency department (ED). METHOD AND FINDINGS: All adult patients with UGIB were identified through diagnostic codes. Hospital mortality was the primary outcome; further bleeding was the secondary outcome. Logistic regression, propensity analyses, and conditional logistic regression were performed to determine factors associated with outcomes. Of 59,188 enrolled patients, 31.6% (n = 18,705) received RBC transfusions within 24 h following presentation to the ED. Hospital mortality was noted in 3.9 and 10.6% of the patients in the non-RBC transfusion and RBC transfusion groups, respectively (P < 0.001). RBC transfusion was associated with increased mortality risk (unadjusted odds ratio (OR) 2.95, 95% confidence interval (CI) 2.75-3.16; P < 0.001) among all patients and in the propensity-matched cohort (unadjusted OR 1.55, 95% CI 1.39-1.72; P < 0.001). Further bleeding was noted in 5.6 and 33.8% of the patients in the non-RBC transfusion and RBC transfusion groups, respectively (P < 0.001). RBC transfusion was associated with increased risk of further bleeding (unadjusted OR 8.60, 95% CI 8.16-9.06; P < 0.001) among all patients and in the propensity-matched cohort (unadjusted OR 2.58, 95% CI 2.37-2.79; P < 0.001). CONCLUSION: RBC transfusion was significantly associated with increased rates of hospital mortality and further bleeding in patients with UGIB. Although our findings have strengths, these results are not generalizable to all patients presenting with UGIB, especially patients presenting with exsanguinating bleeding. Additional prospective trials to guide optimal transfusion strategies in UGIB patients are needed.

Urine-Specific Gravity-Based Hydration Prevents Stroke in Evolution in Patients with Acute Ischemic Stroke.

BACKGROUND: Early neurological deterioration after ischemic stroke (stroke-in-evolution [SIE]) is associated with poorer outcomes. Previous studies have demonstrated a link between hydration status and the development of SIE. In this study, we tested the hypothesis that rehydration therapy, administered on the basis of urine-specific gravity (USG) findings, might reduce the development of SIE. METHODS: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the study group, a USG higher than 1.010 was taken as an indication for rehydration. Control group patients were rehydrated without referring to USG. An increase in National Institutes of Health Stroke Scale (NIHSS) score of 4 or higher within 3 days was defined as having SIE. RESULTS: A total of 445 patients were analyzed, 167 in the study group and 278 in the control group. The proportion of patients who developed SIE was numerically, but not significantly, lower in the study group (5.9%; 10 of 167) compared with the control group (11.5%; 32 of 278). Among patients with a USG higher than 1.010 at admission, the SIE rate was significantly reduced in the study group compared with the control group (6.1% versus 16.0%; P = .021), while the rate of SIE was similar in those with a USG of 1.010 or lower at admission. Multivariate logistic regression analysis confirmed that USG-based hydration was an independent factor associated with reducing SIE. CONCLUSIONS: USG might be a convenient and useful method for guiding fluid therapy in patients with acute ischemic stroke. USG-based hydration reduced the incidence of SIE among patients with a USG higher than 1.010 at admission.

The influence of dehydration on the prognosis of acute ischemic stroke for patients treated with tissue plasminogen activator.

BACKGROUND: Many studies have determined that dehydration is an independent predictor of outcome after ischemic stroke (IS); however, none have determined if the use of thrombolytic therapy modifies the negative impact of poor hydration. To inform the stroke registry established at our institution, we conducted a retrospective study to determine if dehydration remains a negative prognostic factor after IS patients treated with tissue plasminogen activator (tPA). METHODS: Between 2007 and 2012, we recruited 382 subjects; 346 had data available and were divided into 2 groups on the basis of their blood urea nitrogen/creatinine (BUN/Cr) ratio. Dehydrated subjects had a BUN/Cr ratio ≥ 15; hydrated subjects had a BUN/Cr < 15. The primary outcome was impairment at discharge as graded by the Barthel Index (BI) and the modified Rankin Scale (mRS). RESULTS: The dehydration group had a greater mean age; more women; lower mean levels of hemoglobin, triglycerides, and sodium; and higher mean potassium and glucose levels. A favorable outcome as assessed by the mRS (≤2) was significantly less frequent among dehydrated subjects, but a favorable outcome by the BI (≥60) was not. Logistic regression and multivariate models confirmed that dehydration is an independent predictor of poor outcome by both the mRS and the BI; however, it was not predictive when patients were stratified by Trial of Org 10,172 in Acute Stroke Treatment subtype. CONCLUSIONS: Our findings indicate that use of thrombolytic therapy does not eliminate the need to closely monitor hydration status in patients with IS.

Assessing the suitability of sets-based approaches: estimating the discriminative power of risk models for ordinal outcome treatments.

BACKGROUND: In order to evaluate the discrimination performance of an ordinal model for improved disease screening, a new test was proposed where information was obtained across all samples simultaneously. METHODS: The ordinal c-index builds upon the volume under the surface methodology without focusing on the accompanying receiver operating characteristic surfaces. However, it can be simplified to an average of pairwise c-indexes. In this paper, a set-based estimate (information was obtained across all samples simultaneously) was proposed by summing all correctly ordered groups. The asymptotic distribution of this proposed estimate was derived using U-statistics. RESULTS: A predictive model was applied using the blood urea nitrogen/creatinine ratio to discriminate stroke in evolution in acute ischemic stroke patients, which could potentially be life-saving in emergency departments. CONCLUSIONS: By conducting Monte Carlo simulations, it was concluded that the measure proposed herein is a better choice for clinical use because of the asymmetry of the predicted probabilities of groups.