Diffusion-Weighted-Imaging infarct volume measurement tools show discrepancies leading to diverging thrombectomy decisions.

BACKGROUND AND PURPOSE: Recent clinical trials demonstrated the benefit of thrombectomy beyond 6h based on the automated measurement of infarct volume exclusively with the RAPID software. We aimed to compare eight tools commonly used for the measurement of infarct volume and see whether they would lead to similar thrombectomy decisions based on the Diffusion-weighted-imaging or computerized-tomography-perfusion Assessment with clinical mismatch in the triage of Wake-up and late-presenting strokes undergoing Neurointervention with Trevo (DAWN) trial imaging inclusion criteria. MATERIALS AND METHODS: The diffusion-weighted-imaging (DWI) infarct volume of 36 patients was measured with 3 automated tools (including RAPID) and 5 non-automated tools. The agreement for the measurements of DWI infarct volume and the resulting thrombectomy decisions were assessed with intraclass correlation coefficient (ICC) and Fleiss' Kappa (K) statistics. RESULTS: The correlation for the measurement of DWI infarct volume between all 9 tools was excellent (ICC>0.8). After dichotomization, agreement was substantial for any of the cut-points used in DAWN trial. Discrepancies involving at least one of the tools for thrombectomy decisions based on DAWN criteria occurred in one third of cases. Compared with RAPID, the use of any other tool for treatment decision based on DAWN criteria would have led to contradictory decisions in 6% to 19% of cases. CONCLUSION: There are several currently available tools for the measurement of DWI infarct volume with excellent correlation. Despite the high agreement demonstrated in our study, frequent discrepancies between measurements in some dichotomized configurations led to frequent diverging thrombectomy decisions when applying DAWN criteria.

Predictors of Parenchymal Hematoma After Mechanical Thrombectomy: A Multicenter Study

Background and Purpose: Parenchymal hematoma (PH) is a rare but dreadful complication of acute ischemic stroke with unclear underlying mechanisms. We aimed to study the incidence and predictors of PH after mechanical thrombectomy. Methods: Data from a prospective observational multicenter registry was screened to identify acute ischemic stroke patients with an anterior circulation large vessel occlusion who underwent mechanical thrombectomy. Clinical, imaging, and procedural characteristics were used for the analysis, including brain imaging systematically performed at 24 hours. PH occurrence was assessed according to ECASS (European Collaborative Acute Stroke Study) criteria. Univariate and multivariable analyses were performed to identify predictors of PH. Results: A total of 1316 patients were included in the study. PH occurred in 153 out of 1316 patients (11.6%) and was associated with a lower rate of favorable outcome and increased mortality. On multivariable analysis, age (per 1 year increase, odds ratio [OR], 1.01; 95% CI, 1.00­1.03; P=0.05), current smoking (OR, 2.02; 95% CI, 1.32­3.09; P<0.01), admission Alberta Stroke Program Early CT Score (per a decrease of 1 point, OR, 1.70; 95% CI, 1.18­2.44; P<0.01), general anesthesia (OR, 1.98; 95% CI, 1.36­2.90; P<0.001), angiographic poor collaterals (OR, 2.13; 95% CI, 1.36­3.33; P<0.001) and embolization in new territory (OR, 2.94; 95% CI, 1.70­5.10; P<0.001) were identified as independent predictors of PH. Conclusions: PH occurred at a rate of 11.6% after mechanical thrombectomy, with high morbidity and mortality. Our study identified clinical, radiological, and procedural predictors of PH occurrence that can serve as the focus of future periprocedural management studies with the aim of reducing its occurrence.

Association of Blood Pressure During Thrombectomy for Acute Ischemic Stroke With Functional Outcome: A Systematic Review.

Background and Purpose- Optimal blood pressure (BP) targets during mechanical thrombectomy (MT) for acute ischemic stroke (AIS) are unknown, and randomized controlled trials addressing this issue are lacking. We aimed to perform a systematic review of studies evaluating the influence of periprocedural BP on functional outcome after MT. Methods- Studies assessing periprocedural BP effect on functional outcome published after January 1st, 2012 were included in the systematic review. The PRISMA checklist and flow diagram were followed for the design and reporting of this work. Results- Nine studies were included, for a total of 1037 patients. The heterogeneity in findings with respect to BP monitoring and studied parameters precluded a meta-analysis. Mean arterial pressure was the most frequently reported parameter to describe BP variability during MT, and systolic BP was the main parameter used to define periprocedural BP targets. Five studies suggested an association between 3 types of BP drops as predictors of poor functional outcome at 3 months: >40% drop in mean arterial pressure compared with baseline (odds ratio=2.8; [1.09-7.19]; P=0.032), lowest mean arterial pressure before recanalization (odds ratio=1.28; [1.01-1.62] per 10 mm Hg drop below 100 mm Hg; P=0.04), and MAP drops (odds ratio=4.38; [1.53-12.6] for drops >10%). Four studies did not show an association between BP during MT and functional outcome, including 3 studies with strict periprocedural systolic BP targets (within a 140-180 mm Hg). Conclusions- BP drops during MT may be associated with a worse functional outcome. When strict systolic BP targets are achieved, no association between BP and functional outcome was also noted. Both conclusions require further evaluation in randomized studies.

Visual assessment of diffusion weighted imaging infarct volume lacks accuracy and reliability.

PURPOSE: The DAWN trial (Diffusion weighted imaging or CT perfusion Assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing Neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria. MATERIALS AND METHODS: 18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 MR scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters' visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics. RESULTS: The mean accuracy of raters was <90% for all volume cut-points. Inter-rater agreement was below substantial for each DWI infarct volume cut-off points. Intra-rater agreement was substantial for 55-83% of raters, depending on the selected cut-off points. Applying DAWN criteria with visual estimates instead of RAPID measurements led to 19% erroneous thrombectomy decisions, and showed a lack of reproducibility. CONCLUSION: The visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria.

A randomized pragmatic care trial on endovascular acute stroke interventions (EASI): criticisms, responses, and ethics of integrating research and clinical care.

BACKGROUND: The Endovascular Acute Stroke Intervention (EASI) trial was conceived as a pragmatic care trial, designed to integrate trial methods with clinical practice. Reporting the EASI experience was met with objections and criticisms during peer review concerning both scientific and ethical issues. Our goal is to discuss these criticisms in order to promote the pragmatic approach of care trials in outcome-based medical care. METHODS: The comments and criticisms of 11 reviewers from 5 journals were collected and analyzed. The EASI protocol was also compared to the protocols of seven thrombectomy trials using the pragmatic-explanatory continuum indicator summary (PRECIS). RESULTS: Main criticisms of EASI concerned selection criteria that were judged to be too vague and too inclusive, brain and vascular imaging methods that were not sufficiently prescribed by protocol, lack of blinding of outcome assessment, and lack of power. EASI was at the pragmatic end of the spectrum of thrombectomy trials. CONCLUSION: The pragmatic care trial methodology is not currently well-established. More work needs to be done to integrate scientific methods and ethical care in the best medical interest of current patients.

Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial.

PURPOSE: We aimed to assess the agreement between study investigators and the core laboratory (core lab) of a thrombectomy trial for imaging scores. METHODS: The Alberta Stroke Program Early CT Score (ASPECTS), the European Collaborative Acute Stroke Study (ECASS) hemorrhagic transformation (HT) classification, and the Thrombolysis In Cerebral Infarction (TICI) scores as recorded by study investigators were compared with the core lab scores in order to assess interrater agreement, using Cohen's unweighted and weighted kappa statistics. RESULTS: There were frequent discrepancies between study sites and core lab for all the scores. Agreement for ASPECTS and ECASS HT classification was less than substantial, with disagreement occurring in more than one-third of cases. Agreement was higher on MRI-based scores than on CT, and was improved after dichotomization on both CT and MRI. Agreement for TICI scores was moderate (with disagreement occurring in more than 25% of patients), and went above the substantial level (less than 10% disagreement) after dichotomization (TICI 0/1/2a vs 2b/3). CONCLUSION: Discrepancies between scores assessed by the imaging core lab and those reported by study sites occurred in a significant proportion of patients. Disagreement in the assessment of ASPECTS and day 1 HT scores was more frequent on CT than on MRI. The agreement for the dichotomized TICI score (the trial's primary outcome) was substantial, with less than 10% of disagreement between study sites and core lab. TRIAL REGISTRATION NUMBER: NCT02523261, Post-results.

Gadolinium-Enhanced Extracranial MRA Prior to Mechanical Thrombectomy Is Not Associated With an Improved Procedure Speed.

Objectives: To assess whether performing a pre-intervention gadolinium-enhanced extracranial magnetic resonance angiogram (MRA) in addition to intracranial vascular imaging is associated with improved thrombectomy time metrics. Methods: Consecutive patients treated by MT at a large comprehensive stroke center between January 2012 and December 2017 who were screened using pre-intervention MRI were included. Patients characteristics and procedural data were collected. Univariate and multivariate analysis were performed to compare MT speed, efficacy, complications, and clinical outcomes between patients with and without pre-intervention gadolinium-enhanced extracranial MRA. Results: A total of 912 patients were treated within the study period, including 288 (31.6%) patients with and 624 (68.4%) patients without extracranial MRA. Multivariate analysis showed no significant difference between groups in groin puncture to clot contact time (RR = 0.93 [0.85-1.02], p = 0.14) or to recanalization time (RR = 0.92 [0.83-1.03], p = 0.15), rates of successful recanalization (defined as a mTICI 2b or 3, RR = 0.93 [0.62-1.42], p = 0.74), procedural complications (RR = 0.81 [0.51-1.27], p = 0.36), and good clinical outcome (defined by a mRS ≤ 2 at 3 months follow-up, RR = 1.05 [0.73-1.52], p = 0.79). Conclusion: Performing a pre-intervention gadolinium-enhanced extracranial MRA in addition to non-contrast intracranial MRA at stroke onset does not seem to be associated with a delay or shortening of procedure times.

Cervical Internal Carotid Occlusion versus Pseudo-occlusion at CT Angiography in the Context of Acute Stroke: An Accuracy, Interobserver, and Intraobserver Agreement Study.

Purpose To evaluate the diagnostic accuracy and reliability of computed tomographic (CT) angiography to distinguish true cervical internal carotid artery (ICA) occlusion from pseudo-occlusion (defined as an isolated intracranial thrombus that impedes ascending blood flow) in the context of acute stroke. Materials and Methods This was a retrospective study of patients who underwent thrombectomy with preprocedural CT angiography that helps to demonstrate a lack of attenuation in the cervical ICA on the symptomatic side (24 men and 13 women; mean age, 63 years; age range, 30-86 years). Seven readers, including five neuroradiologists and two interventional neuroradiology fellows, independently reviewed the CT angiography images to assess whether there was true cervical ICA occlusion. Their results were compared with digital subtraction angiography (DSA) as the reference standard. Sensitivity and specificity for detecting true occlusion as well as accuracy and diagnostic odds ratio were calculated, with inter- and intraobserver κ statistics. Results Cervical ICA pseudo-occlusion occurred in 12 of 37 patients (32.4%) with nonattenuation of the cervical ICA on the symptomatic side. Interobserver agreement coefficients did not reach the substantial value of 0.61 for either pairs or groups of readers. The cohort's average sensitivity and specificity was 68% (95% confidence interval [CI]: 59%, 76%) and 75% (95% CI: 71%, 80%), respectively, with a diagnostic odds ratio of 8 (95% CI: 3, 18) and only fair interobserver agreement (κ = 0.32; 95% CI: 0.16, 0.47). Conclusion In the context of acute ischemic stroke with ipsilateral ICA nonattenuation at single-phase CT angiography, even specialized radiologists may not reliably distinguish true cervical occlusion from pseudo-occlusion. © RSNA, 2017 Online supplemental material is available for this article.

DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) Mismatch in Thrombectomy Candidates: An Intrarater and Interrater Agreement Study.

BACKGROUND AND PURPOSE: We aimed to study the intrarater and interrater agreement of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) mismatch in patients with acute ischemic stroke referred for mechanical thrombectomy. METHODS: Eighteen raters independently scored anonymized magnetic resonance imaging scans of 30 participants from a multicentre thrombectomy trial, in 2 different reading sessions. Agreement was measured using Fleiss κ and Cohen κ statistics. RESULTS: Interrater agreement for DWI-ASPECTS was slight (κ=0.17 [0.14-0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement. Dichotomization of the DWI-ASPECTS (0-5 versus 6-10 or 0-6 versus 7-10) increased the interrater agreement to a substantial level (κ=0.62 [0.48-0.75] and 0.68 [0.55-0.79], respectively) and more raters reached a substantial (or higher) intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR mismatch was moderate (κ=0.43 [0.33-0.57]); 11 raters (61.1%) reached a substantial (or higher) intrarater agreement. CONCLUSIONS: Agreement between clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to make repeatable clinical decisions in mechanical thrombectomy. The dichotomization of the DWI-ASPECTS (0-5 versus 0-6 or 0-6 versus 7-10) improved interrater and intrarater agreement, however, its relevance for patients selection for mechanical thrombectomy needs to be validated in a randomized trial.

Endovascular thrombectomy and medical therapy versus medical therapy alone in acute stroke: A randomized care trial.

BACKGROUND: Until recently, the benefits of endovascular treatment in stroke were not proven. Care trials have been designed to simultaneously offer yet-to-be validated interventions and verify treatment outcomes. Our aim was to implement a care trial for patients with acute ischemic stroke. METHODS: The study was offered to all patients considered for endovascular management of acute ischemic stroke in one Canadian hospital. Inclusion criteria were broad: onset of symptoms≤5h or at any time in the presence of clinical-imaging mismatch and suspected or demonstrated proximal large vessel occlusion. Exclusion criteria were few: established infarction or hemorrhagic transformation of the target symptomatic territory and poor 3-month prognosis. The primary outcome was mRS≤2 at 3 months. Patients were randomly allocated to standard care or standard care plus endovascular treatment. ClinicalTrials.gov: Identifier NCT02157532. RESULTS: Seventy-seven patients were recruited in 19 months (March 2013-October 2014) at a single center. Randomized allocation was interrupted when other trials showed the benefits of endovascular therapy. At 3 months, 20 of 40 patients (50.0%; 95% CI: 35%-65%) in the intervention group had reached the primary outcome, compared to 14 of 37 patients (37.8%; 95% CI: 24%-54%) in the control group (P=0.36). Eleven patients in the intervention group died within 3 months compared to 9 patients in the standard care group. CONCLUSION: A care trial was implemented to offer verifiable care to acute stroke patients. This approach offers a promising means to manage clinical dilemmas and guide uncertain practices.

Unexpected complications with head and neck hydrogel microsphere particle embolization: A case series and a technical note.

Endovascular particle embolization is a common procedure with a relatively safe profile. We report here four cases in which cranial nerves, skin and mucosal ischemic complications occurred with the use of hydrogel microspheres (250-500 µm in size). Given the compressibility and higher penetration potential of microsphere particles compared with polyvinyl alcohol particles of similar size, we suggest oversizing hydrogel microsphere particles for head and neck embolizations.

Embolization with larger-caliber coils can increase packing density: Evidence from the pilot phase of a randomized trial.

Background and purpose Endovascular coil embolization of cerebral aneurysms is associated with suboptimal angiographic results in up to 20-30% of patients. Coil packing density has been used as an index of the success of the initial procedure. The trial sought to study the effects of using 15-caliber coils, as compared with 10-caliber coils, on packing density. Methods Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) is an investigator-initiated multicenter prospective, randomized, controlled clinical trial. Patients are randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils and 10-caliber coils if necessary (intervention group) in 4-12-mm aneurysms. The endpoint of the pilot phase of the trial was the capacity to increase packing density of the initial procedure, calculated using a mathematical transformation of the dimensions entered into the case report forms. Secondary outcomes included the total number of coils used per aneurysm, total fluoroscopy time, initial angiographic outcomes and any adverse or undesirable event. Results Seventy patients were recruited between June 2014 and November 2015. Compared with 10-caliber coils, the 15-caliber coil group had a higher median packing density (44% vs 24%, p = 0.017). Results of other outcome measures were similar for the two groups. Conclusion Coiling of small and medium aneurysms randomized to 15-caliber coils achieved higher packing densities compared with coiling using 10-caliber coils.

Endovascular treatment of aneurysms and platinum coil caliber: Study protocol of a randomized, controlled trial.

BACKGROUND: Endovascular coil embolization of cerebral aneurysms is an effective treatment for the prevention of aneurysm rebleeding after subarachnoid hemorrhage. It is also often used in unruptured aneurysms, but it is associated with aneurysm remnants and recurrences in up to 20%-33% of patients. We hypothesized that better aneurysm occlusion rates can be achieved with coils of larger caliber. METHODS: The Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) trial is an investigator-initiated, multicenter, prospective, randomized, controlled clinical trial. To test the hypothesis that 15-caliber coiling systems are superior to 10-caliber coils, 564 patients with aneurysms measuring 4-12 mm will be randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils (intervention group). The primary efficacy endpoint of the trial is the occurrence of a major recurrence or a residual aneurysm at one year. A pilot phase of 165 patients will be conducted to verify feasibility of the coiling strategy, compliance to treatment allocation, safety of a 15-caliber platinum coil embolization strategy, recruitment rates, and the capacity to improve packing density. DISCUSSION: The DELTA trial will test the hypothesis that the use of coils of larger caliber can improve angiographic results of endovascular coiling.

Early CT changes in patients admitted for thrombectomy: Intrarater and interrater agreement.

OBJECTIVE: To systematically review the literature and assess agreement on the Alberta Stroke Program Early CT Score (ASPECTS) among clinicians involved in the management of thrombectomy candidates. METHODS: Studies assessing agreement using ASPECTS published from 2000 to 2015 were reviewed. Fifteen raters reviewed and scored the anonymized CT scans of 30 patients recruited in a local thrombectomy trial during 2 independent sessions, in order to study intrarater and interrater agreement. Agreement was measured using intraclass correlation coefficients (ICCs) and Fleiss kappa statistics for ASPECTS and dichotomized ASPECTS at various cutoff values. RESULTS: The review yielded 30 articles reporting 40 measures of agreement. Populations, methods, analyses, and results were heterogeneous (slight to excellent agreement), precluding a meta-analysis. When analyzed as a categorical variable, intrarater agreement was slight to moderate (κ = 0.042-0.469); it reached a substantial level (κ > 0.6) in 11/15 raters when the score was dichotomized (0-5 vs 6-10). The interrater ICCs varied between 0.672 and 0.811, but agreement was slight to moderate (κ = 0.129-0.315). Even in the best of cases, when ASPECTS was dichotomized as 0-5 vs 6-10, interrater agreement did not reach a substantial level (κ = 0.561), which translates into at least 5 of 15 raters not giving the same dichotomized verdict in 15% of patients. CONCLUSIONS: In patients considered for thrombectomy, there may be insufficient agreement between clinicians for ASPECTS to be reliably used as a criterion for treatment decisions.

Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator-Eligible Stroke Patients When Clinical Impression Is Stroke Mimic.

BACKGROUND AND PURPOSE: Stroke mimics (SM) challenge the initial assessment of patients presenting with possible acute ischemic stroke (AIS). When SM is considered likely, intravenous tissue-type plasminogen activator (tPA) may be withheld, risking an opportunity to treat AIS. Although computed tomography is routinely used for tPA decision making, magnetic resonance imaging (MRI) may diagnose AIS when SM is favored but not certain. We hypothesized that a hyperacute MRI (hMRI) protocol would identify tPA-eligible AIS patients among those initially favored to have SM. METHODS: A streamlined hMRI protocol was designed based on barriers to rapid patient transport, MRI acquisition, and post-MRI tPA delivery. Neurologists were trained to order hMRI when SM was favored and tPA was being withheld. The use of hMRI for tPA decision making, door-to-needle times, and outcomes were compared before hMRI implementation (pre-hMRI: August 1, 2011 to July 31, 2013) and after (post-hMRI, August 1, 2013, to January 15, 2015). RESULTS: Post hMRI, 57 patients with suspected SM underwent hMRI (median MRI-order-to-start time, 29 minutes), of whom, 11 (19%) were diagnosed with AIS and 7 (12%) received tPA. Pre-hMRI, no tPA-treated patients were screened with hMRI. Post hMRI, 7 of 106 (6.6%) tPA-treated patients underwent hMRI to aid in decision making because of suspected SM (0% versus 6.6%; P=0.001). To ensure standard care was maintained after implementing the hMRI protocol, pre- versus post-hMRI tPA-treated cohorts were compared and did not differ: door-to-needle time (39 versus 37 minutes; P=0.63), symptomatic hemorrhage rate (4.5% versus 1.9%; P=0.32), and favorable discharge location (85% versus 89%; P=0.37). CONCLUSIONS: A streamlined hMRI protocol permitted tPA administration to a small, but significant, subset of AIS patients initially considered to have SM.

Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

BACKGROUND AND PURPOSE: Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. METHODS: Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. RESULTS: The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. CONCLUSIONS: OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

Reducing door-to-needle times using Toyota's lean manufacturing principles and value stream analysis.

BACKGROUND AND PURPOSE: Earlier tissue-type plasminogen activator (tPA) treatment for acute ischemic stroke increases efficacy, prompting national efforts to reduce door-to-needle times. We used lean process improvement methodology to develop a streamlined intravenous tPA protocol. METHODS: In early 2011, a multidisciplinary team analyzed the steps required to treat patients with acute ischemic stroke with intravenous tPA using value stream analysis (VSA). We directly compared the tPA-treated patients in the "pre-VSA" epoch with the "post-VSA" epoch with regard to baseline characteristics, protocol metrics, and clinical outcomes. RESULTS: The VSA revealed several tPA protocol inefficiencies: routing of patients to room, then to CT, then back to the room; serial processing of workflow; and delays in waiting for laboratory results. On March 1, 2011, a new protocol incorporated changes to minimize delays: routing patients directly to head CT before the patient room, using parallel process workflow, and implementing point-of-care laboratories. In the pre and post-VSA epochs, 132 and 87 patients were treated with intravenous tPA, respectively. Compared with pre-VSA, door-to-needle times and percent of patients treated ≤60 minutes from hospital arrival were improved in the post-VSA epoch: 60 minutes versus 39 minutes (P<0.0001) and 52% versus 78% (P<0.0001), respectively, with no change in symptomatic hemorrhage rate. CONCLUSIONS: Lean process improvement methodology can expedite time-dependent stroke care without compromising safety.

Morphological and biochemical alterations in the jejunum following iodoacetamide-induced colitis in rats.

This study aims to describe the morphological alterations in the small and large intestines as well as the expression of some enterocyte enzymes and carriers in a rat model of iodoacetamide-induced colitis. Biopsies from the large and small intestines were taken at 1, 2, 4, 8, and 16 days postinduction and studied by light microscopy. The expressions of lactase, sucrase, aminopeptidase, and Glut-5 in the jejunum were studied by immunohistochemistry. Gene expressions of enterocyte lactase and sucrase were determined by RT-PCR using specific oligonucleotides. Microscopic examination of the large intestines revealed manifestations concordant with inflammation. Such alterations peaked at 2 days, were maintained to a lesser extent for 4 days, regressed by 8 days, and healed by 16 days. In the jejunum, the expression of lactase, sucrase, and aminopeptidase decreased 2 days after colitis induction, and recovered 2 days later. Similarly, Glut-5 expression decreased transiently with partial recovery by day 8. Compared with sham, gene expression of jejunal brush border enzymes sucrase and lactase showed a 4-fold increase in lactase and a 9-fold increase in sucrase after 4 days. We conclude that colitis can induce significant functional abnormalities in distant noninflamed small bowel regions.