Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.

Cytoprotective Agents in Stroke: Still Uncertainty in the Next Frontier.

INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Tools for assessing health research partnership outcomes and impacts: a systematic review.

OBJECTIVE: To identify and assess the globally available valid, reliable and acceptable tools for assessing health research partnership outcomes and impacts. METHODS: We searched Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO from origin to 2 June 2021, without limits, using an a priori strategy and registered protocol. We screened citations independently and in duplicate, resolving discrepancies by consensus and retaining studies involving health research partnerships, the development, use and/or assessment of tools to evaluate partnership outcomes and impacts, and reporting empirical psychometric evidence. Study, tool, psychometric and pragmatic characteristics were abstracted using a hybrid approach, then synthesized using descriptive statistics and thematic analysis. Study quality was assessed using the quality of survey studies in psychology (Q-SSP) checklist. RESULTS: From 56 123 total citations, we screened 36 027 citations, assessed 2784 full-text papers, abstracted data from 48 studies and one companion report, and identified 58 tools. Most tools comprised surveys, questionnaires and scales. Studies used cross-sectional or mixed-method/embedded survey designs and employed quantitative and mixed methods. Both studies and tools were conceptually well grounded, focusing mainly on outcomes, then process, and less frequently on impact measurement. Multiple forms of empirical validity and reliability evidence was present for most tools; however, psychometric characteristics were inconsistently assessed and reported. We identified a subset of studies (22) and accompanying tools distinguished by their empirical psychometric, pragmatic and study quality characteristics. While our review demonstrated psychometric and pragmatic improvements over previous reviews, challenges related to health research partnership assessment and the nascency of partnership science persist. CONCLUSION: This systematic review identified multiple tools demonstrating empirical psychometric evidence, pragmatic strength and moderate study quality. Increased attention to psychometric and pragmatic requirements in tool development, testing and reporting is key to advancing health research partnership assessment and partnership science. PROSPERO CRD42021137932.

Outcomes of endovascular treatment for acute large-vessel ischaemic stroke more than 6 h after symptom onset.

BACKGROUND AND OBJECTIVES: Benefit from endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) is well demonstrated. Furthermore, emerging evidence supports efficacy in appropriately selected patients treated beyond current recommendations of 6 h. We evaluated clinical outcomes in patients undergoing late EVT at our institution. METHODS: Retrospective review of prospectively collected clinical database on 355 patients who underwent EVT for LVO AIS. Data collected consisted of patient demographics, radiological findings and outcome details. Outcomes, including 90-day functional status, recanalization, symptomatic intracranial haemorrhage (sICH) and 90-day mortality, for patients undergoing EVT <6 h, >6 h, and >7.3 h, were compared. RESULTS: A total of 355 patients underwent EVT for LVO AIS at our institution during the review period, with 74 (21%) patients treated ≥6 h from symptom onset. Successful recanalization was achieved in 285 (80%) patients, with 228 (81%) achieving a mTICI ≥2b in the <6 h group, and 57 (77%) in the >6 h group (P = 0.429). Ninety-day functional independence (mRS 0-2) was achieved in 162 (46%) patients, with 130 (46%) achieving a mRS of 0-2 in the <6 h group, and 32 (43%) in the >6 h group (P = 0.643). No significant differences were found in rates of sICH or 90-day mortality. No significant differences in functional independence, recanalization rates, sICH or mortality were identified in patients treated with EVT >7.3 h compared to <7.3 h. CONCLUSIONS: In appropriately selected patients, EVT >6 h was associated with comparable outcomes to those treated <6 h. These data support a physiological approach to patient selection.

Covert stroke after non-cardiac surgery: a prospective cohort study.

BACKGROUND: Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery. METHODS: We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke. RESULTS: We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5-17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12). CONCLUSIONS: This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes. CLINICAL TRIAL REGISTRATION: NCT01369537.

The prevalence of incidental findings in multiple sclerosis patients.

BACKGROUND: Incidental findings arising from imaging research have important implications for patient safety. Magnetic resonance imaging is widespread in multiple sclerosis (MS) studies and care, yet the prevalence rate of incidental findings in MS is poorly defined. The absence of such reports in the MS literature suggests that such findings may be deemed inappropriate for documentation in research publications, or possibly, not fully reported at all. OBJECTIVE: We sought to document incidental findings from a study designed to detect features of chronic cerebrospinal venous insufficiency (CCSVI) in MS patients and control subjects. METHODS: Magnetic resonance images were obtained as part of a prospective study conducted between October 2010 and September 2012. Patients with MS (relapsing-remitting, primary progressive, secondary progressive), clinically isolated syndromes, and neuromyelitis optica and age/sex-matched healthy controls were included. All images were reviewed by neuro-radiologists for quality-control purposes. RESULTS: Magnetic resonance imaging was successfully obtained in 166 participants (110 patients, 56 controls). Incidental abnormalities (n = 33) were detected in 15% of patients (n = 17) and 27% of controls (n = 15), comprising 19% overall (n = 32). CONCLUSIONS: The prevalence of incidental findings from the MS population was not significantly different from the control population. However, the overall prevalence was high and warrants a careful management strategy for future imaging studies.Prévalence des découvertes fortuites chez les patients atteints de sclérose en plaques.

CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. MATERIALS AND METHODS: Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. RESULTS: CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CONCLUSIONS: CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

Automated Segmentation of Intracranial Thrombus on NCCT and CTA in Patients with Acute Ischemic Stroke Using a Coarse-to-Fine Deep Learning Model.

BACKGROUND AND PURPOSE: Identifying the presence and extent of intracranial thrombi is crucial in selecting patients with acute ischemic stroke for treatment. This article aims to develop an automated approach to quantify thrombus on NCCT and CTA in patients with stroke. MATERIALS AND METHODS: A total of 499 patients with large-vessel occlusion from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial were included. All patients had thin-section NCCT and CTA images. Thrombi contoured manually were used as reference standard. A deep learning approach was developed to segment thrombi automatically. Of 499 patients, 263 and 66 patients were randomly selected to train and validate the deep learning model, respectively; the remaining 170 patients were independently used for testing. The deep learning model was quantitatively compared with the reference standard using the Dice coefficient and volumetric error. The proposed deep learning model was externally tested on 83 patients with and without large-vessel occlusion from another independent trial. RESULTS: The developed deep learning approach obtained a Dice coefficient of 70.7% (interquartile range, 58.0%-77.8%) in the internal cohort. The predicted thrombi length and volume were correlated with those of expert-contoured thrombi (r = 0.88 and 0.87, respectively; P < .001). When the derived deep learning model was applied to the external data set, the model obtained similar results in patients with large-vessel occlusion regarding the Dice coefficient (66.8%; interquartile range, 58.5%-74.6%), thrombus length (r = 0.73), and volume (r = 0.80). The model also obtained a sensitivity of 94.12% (32/34) and a specificity of 97.96% (48/49) in classifying large-vessel occlusion versus non-large-vessel occlusion. CONCLUSIONS: The proposed deep learning method can reliably detect and measure thrombi on NCCT and CTA in patients with acute ischemic stroke.

Outcomes with Endovascular Treatment of Patients with M2 Segment MCA Occlusion in the Late Time Window.

BACKGROUND AND PURPOSE: Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset. MATERIALS AND METHODS: Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion. RESULTS: Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%, P = .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29). CONCLUSIONS: In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.

Subacute seizure incidence in thrombolysis-treated ischemic stroke patients.

BACKGROUND: To assess the incidence of seizures in acute ischemic stroke patients treated with chemical (tPA) thrombolysis. METHODS: Retrospective study including all thrombolysis patients treated in Calgary between January 1, 2001, and October 31, 2006. Descriptive statistics and age/sex-adjusted P values were calculated. RESULTS: Of 400 eligible patients (median age 74.0 years, range: 24-77), 16 (4%) developed post-stroke seizures: 10 (62.5%) within one week (early) and 6 (37.5%) after 1 week but within the hospital stay (late). Single-vessel anterior circulation involvement (93.8% vs. 87%, P = 0.34) and hemorrhage (37.5% vs. 20%, P = 0.15) were more common in those with compared to without seizures but did not reach statistical significance. Atrial fibrillation was more common in those with (56.3%) than without (36.1%) seizures (P = 0.04). Death during admission was more likely (P = 0.03) in those who sustained seizures (37.5%) compared to those without seizures (17.6%). CONCLUSIONS: In this cohort of tPA-treated patients, post-stroke seizures were associated with atrial fibrillation and early mortality.

Prevalence of Intracranial Atherosclerotic Disease in Patients with Low-Risk Transient or Persistent Neurologic Events.

BACKGROUND AND PURPOSE: There are limited data on the prevalence and outcome of intracranial atherosclerotic disease in patients with low-risk transient or persistent minor neurologic events. We sought to determine the prevalence and risk factors associated with intracranial atherosclerotic disease in patients with low-risk transient or persistent neurologic events. MATERIALS AND METHODS: Participants with available intracranial vascular imaging from the Diagnosis of Uncertain-Origin Benign Transient Neurologic Symptoms (DOUBT) study, a large prospective multicenter cohort study, were included in this post hoc analysis. The prevalence of intracranial atherosclerotic disease of ≥50% was determined, and the association with baseline characteristics and DWI lesions was evaluated using logistic regression. RESULTS: We included 661 patients with a median age of 62 years (interquartile range, 53-70 years), of whom 53% were women. Intracranial atherosclerotic disease was found in 81 (12.3%) patients; asymptomatic intracranial atherosclerotic disease alone, in 65 (9.8%); and symptomatic intracranial atherosclerotic disease, in 16 (2.4%). The most frequent location was in the posterior cerebral artery (29%). Age was the only factor associated with any intracranial atherosclerotic disease (adjusted OR, 1.9 for 10 years increase; 95% CI, 1.6-2.5). Multivariable logistic regression showed a strong association between intracranial atherosclerotic disease and the presence of acute infarct on MR imaging (adjusted OR, 3.47; 95% CI, 1.91-6.25). CONCLUSIONS: Intracranial atherosclerotic disease is not rare in patients with transient or persistent minor neurologic events and is independently associated with the presence of MR imaging-proved ischemia in this context. Evaluation of the intracranial arteries could be valuable in establishing the etiology of such low-risk events.

Outcomes after carotid angioplasty and stenting in symptomatic octogenarians.

OBJECTIVE: Octogenarians were excluded from participation in many carotid endarterectomy trials due to the high complication rates observed in past studies. However, stroke resulting from carotid stenosis is expected to increase with the aging population. Moreover, advances in Carotid Angioplasty and Stenting (CAS) techniques have resulted in perceived improved safety of this procedure. We sought to review our experience with carotid stenting in symptomatic octogenarians with an emphasis on short-term outcomes and complications. METHODS: This is a retrospective longitudinal cohort study of all symptomatic patients who underwent CAS in our center between 1997 and 2007. Thirty-day stroke and death rates, and length of hospitalization were compared between the symptomatic octogenarians and non-octogenarians. RESULTS: A total of 214 procedures were performed on 211 symptomatic patients (56 females). Fifty-nine patients (14 females) were octogenarians. The median (interquartile range) age on procedure date for the octogenarian cohort was 83 (4) years. Periprocedural death occurred in two (3.4%) octogenarians and five (3.3%) non-octogenarians (p = 0.97). At 30 days from the procedure, stroke occurred in four (6.8%) octogenarians and seven (4.6%) non-octogenarians (p= 0.52). The mean hospital stay (4.8 days) was not different between the two cohorts. Age was not a predictor of the 30-day risk of composite stroke or death. CONCLUSION: The complications rate observed in octogenarians was not significantly higher than non-octogenarians. Our findings suggest that octogenarians should be included in randomized trials examining CAS to better define the risk-benefit profile of this procedure in the elderly.

The ASPIRE approach for TIA risk stratification.

BACKGROUND: The risk of stroke after transient ischemic attack (TIA) is elevated in the days to weeks after TIA. A variety of prediction rules to predict stroke risk have been suggested. In Alberta a triage algorithm to facilitate urgent access based on risk level was agreed upon for the province. Patients with ABCD2 score ≥ 4, or motor or speech symptoms lasting greater than five minutes, or with atrial fibrillation were considered high risk (the ASPIRE approach). We assessed the ability of the ASPIRE approach to identify patients at risk for stroke. METHODS: We retrospectively reviewed charts from 573 consecutive patients diagnosed with TIA in Foothills Hospital emergency room from 2002 through 2005. We recorded clinical and event details and identified the risk of stroke at three months. RESULTS: Among 573 patients the 90-day risk of stroke was 4.7% (95% CI 3.0%, 6.4%). 78% of the patients were identified as high risk using this approach. In patients defined as high risk on the ASPIRE approach there was a 6.3% (95% CI 4.2%, 8.9%) risk of stroke. In patients defined as low risk using the ASPIRE approach there were no recurrent strokes (100% negative predictive value). In contrast, two patients with low ABCD2 scores (ABCD2 score < 4) suffered recurrent strokes. CONCLUSION: The ASPIRE approach has a perfect negative predictive value in the population in predicting stroke. However, this high sensitivity comes at a cost of identifying most patients as high risk.

Strength of Association between Infarct Volume and Clinical Outcome Depends on the Magnitude of Infarct Size: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0-2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6-92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0-15 mL, 15.1-70 mL, 70.1-200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0-15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15-200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

Carotid stenting in asymptomatic carotid stenosis: the Calgary experience.

BACKGROUND: Although carotid endarterectomy is considered the 'gold standard' for standard risk symptomatic patients, the treatment of choice for asymptomatic patients remains controversial. Carotid stenting has demonstrated real-world outcomes consistent with established guidelines for carotid endarterectomy in asymptomatic high-surgical risk patients in recent prospective multicenter trials. We describe our experience with asymptomatic patients who underwent carotid stenting at our center in a routine clinical setting. METHODS: This is a retrospective, longitudinal cohort study of patients who underwent carotid angioplasty and stenting at the Foothills Medical Center, Calgary, Canada between 1997 and 2007. The qualifying events were categorized as symptomatic and asymptomatic. The procedures were performed by four experienced neurointerventionists. The primary outcome was stroke or death at 30-day follow- up. RESULTS: 243 patients underwent 255 carotid stenting procedures. Their ages ranged from 50 to 83 years; the mean age was 72.0 ± 9.3 years; 67(26.3%) were women. Forty one patients (16.1%) were asymptomatic; 214 patients (83.9%) were symptomatic. The patients in the asymptomatic group were significantly younger - 66.0 ± 8.8 years compared to patients in the symptomatic group 73.2 ± 8.9 years (p < 0.0001). Intraprocedurally one minor stroke (2.4%) occurred in the asymptomatic group. At 30-day follow-up, no deaths or further strokes were noted in the asymptomatic group; while eight deaths, six major and seven minor strokes occurred in the symptomatic group (p = 0.22). CONCLUSION: Carotid stenting appears to be a safe procedure in asymptomatic patients with severe carotid stenosis in routine clinical settings as witnessed in this single center study.

Endovascular Treatment Decisions in Patients with M2 Segment MCA Occlusions.

BACKGROUND AND PURPOSE: Endovascular therapy in acute ischemic stroke is rapidly evolving. We explored physicians' treatment attitudes and practice in patients with acute ischemic stroke due to M2 occlusion, given the absence of Level-1 guidelines. MATERIALS AND METHODS: We conducted an international multidisciplinary survey among physicians involved in acute stroke care. Respondents were presented with 10 of 22 case scenarios (4 with proximal M2 occlusions and 1 with a small-branch M2 occlusion) and asked about their treatment approach under A) current local resources, and B) assumed ideal conditions (no monetary or infrastructural restraints). Overall treatment decisions were evaluated; subgroup analyses by physician and patient baseline characteristics were performed. RESULTS: A total of 607 physicians participated. Most of the respondents decided in favor of endovascular therapy in M2 occlusions, both under current local resources and assumed ideal conditions (65.4% versus 69.6%; P = .017). Under current local resources, older patient age (P < .001), longer time since symptom onset (P < .001), high center endovascular therapy volume (P < .001), high personal endovascular therapy volume (P = .005), and neurosurgeons (P < .001) were more likely to favor endovascular therapy. European respondents were less likely to favor endovascular therapy (P = .001). Under assumed ideal conditions, older patient age (P < .001), longer time since symptom onset (P < .001), high center endovascular therapy volume (P = .041), high personal endovascular therapy volume (P = .002), and Asian respondents were more likely to favor endovascular therapy (P = .037). Respondents with more experience (P = .048) and high annual stroke thrombolysis treatment volume (P = .001) were less likely to favor endovascular therapy. CONCLUSIONS: Patients with M2 occlusions are considered appropriate candidates for endovascular therapy by most respondents in this survey, especially by those performing endovascular therapy more often and those practicing in high-volume centers.

Dynamic CTA-Derived Perfusion Maps Predict Final Infarct Volume: The Simple Perfusion Reconstruction Algorithm.

BACKGROUND AND PURPOSE: Infarct core volume measurement using CTP (CT perfusion) is a mainstay paradigm for stroke treatment decision-making. Yet, there are several downfalls with cine CTP technology that can be overcome by adopting the simple perfusion reconstruction algorithm (SPIRAL) derived from multiphase CTA. We compare SPIRAL with CTP parameters for the prediction of 24-hour infarction. MATERIALS AND METHODS: Seventy-two patients had admission NCCT, multiphase CTA, CTP, and 24-hour DWI. All patients had successful/quality reperfusion. Patient-level and cohort-level receiver operator characteristic curves were generated to determine accuracy. A 10-fold cross-validation was performed on the cohort-level data. Infarct core volume was compared for SPIRAL, CTP-time-to-maximum, and final DWI by Bland-Altman analysis. RESULTS: When we compared the accuracy in patients with early and late reperfusion for cortical GM and WM, there was no significant difference at the patient level (0.83 versus 0.84, respectively), cohort level (0.82 versus 0.81, respectively), or the cross-validation (0.77 versus 0.74, respectively). In the patient-level receiver operating characteristic analysis, the SPIRAL map had a slightly higher, though nonsignificant (P < .05), average receiver operating characteristic area under the curve (cortical GM/WM, r = 0.82; basal ganglia = 0.79, respectively) than both the CTP-time-to-maximum (cortical GM/WM = 0.82; basal ganglia = 0.78, respectively) and CTP-CBF (cortical GM/WM = 0.74; basal ganglia = 0.78, respectively) parameter maps. The same relationship was observed at the cohort level. The Bland-Altman plot limits of agreement for SPIRAL and time-to-maximum infarct volume were similar compared with 24-hour DWI. CONCLUSIONS: We have shown that perfusion maps generated from a temporally sampled helical CTA are an accurate surrogate for infarct core.

Acute And Sub-Acute Reconstruction Of Periorbital Thermal Burns Involving The Anterior Lamella Of The Eyelid With Simultaneous Fullthickness Skin Grafting And Amniotic Membrane Grafting.

Thermal burns of the periorbital region offer a particular challenge to surgeons in terms of satisfactory operative reconstruction. Several approaches currently exist, including full-thickness skin grafting following scar excision. The authors present a novel technique for the reconstruction of periorbital thermal burns involving the anterior lamella of the eyelid with simultaneous full-thickness skin grafting and amniotic membrane grafting. A retrospective review of six patients with periorbital thermal burn injury involving the anterior lamella of the eyelid(s) who underwent operative reconstruction utilizing this technique was performed. The operative and post-surgical outcomes were evaluated. In total, sixteen graft sites were examined. All graft sites demonstrated appropriate coverage and healthy re-epithelialization over the previously necrotic and burned areas. No evidence of cicatricial changes or lagophthalmos was noted. The postoperative outcomes demonstrate excellent functionality and cosmesis. By providing acute reconstruction, the risk of ophthalmic damage and vision loss secondary to cicatricial eyelid changes may be avoided. Additionally, utilizing only a minimal amount of tissue for reconstruction preserves vital skin. This analysis demonstrates the viability of simultaneous full-thickness skin grafting and amniotic membrane grafting for the acute and sub-acute reconstruction of periorbital thermal burn injury.

Les brûlures thermiques de la région périorbitaire représentent pour les chirurgiens un défi particulier pour obtenir une reconstruction de qualité. Plusieurs approches existent actuellement, dont la greffe de peau totale après excision de la cicatrice. Les auteurs présentent une nouvelle technique de reconstruction des brûlures thermiques périorbitaires impliquant la lamelle antérieure de la paupière avec greffe de peau totale et greffe de membrane amniotique simultanées. Une revue rétrospective a été réalisée sur six patients présentant une brûlure thermique périorbitaire impliquant la lamelle antérieure de la/les paupière(s), reconstruits en utilisant cette technique. Les résultats opératoires et post-chirurgicaux ont été évalués. Au total, seize sites de greffe ont été examinés. Tous les sites de greffe ont démontré une couverture appropriée et une réépithélialisation saine sur les zones auparavant nécrotiques et brûlées. Aucun signe de remaniements cicatriciels ou de lagophtalmie n'a été noté. Les résultats postopératoires sont excellents sur le plan fonctionnel et esthétique. En assurant une reconstruction à la phase aiguë, le risque de lésions ophtalmiques et de perte de vision secondaire à des modifications de la paupière cicatricielle peut être évité. De plus, l'utilisation d'une quantité minimale de tissu pour la reconstruction préserve le capital cutané. Cette analyse démontre la viabilité de la greffe de peau totale et la greffe de membrane amniotique simultanées, pour la reconstruction aiguë et subaiguë de brûlure thermique périorbitaire.

How Do Physicians Approach Intravenous Alteplase Treatment in Patients with Acute Ischemic Stroke Who Are Eligible for Intravenous Alteplase and Endovascular Therapy? Insights from UNMASK-EVT.

BACKGROUND AND PURPOSE: With increasing use of endovascular therapy, physicians' attitudes toward intravenous alteplase in endovascular therapy-eligible patients may be changing. We explored current intravenous alteplase treatment practices of physicians in endovascular therapy- and alteplase-eligible patients with acute stroke using prespecified case scenarios and compared how their current local treatment practices differ compared with an assumed ideal environment. MATERIALS AND METHODS: In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 of 22 case scenarios, among them 14 with guideline-based alteplase recommendations (9 with level 1A and 5 with level 2B recommendation) and were asked how they would treat the patient: A) under their current local resources, and B) under assumed ideal conditions. Answer options were the following: 1) anticoagulation/antiplatelet therapy, 2) endovascular therapy, 3) endovascular therapy plus intravenous alteplase, and 4) intravenous alteplase. Decision rates were calculated, and multivariable regression analysis was performed to determine variables associated with the decision to abandon intravenous alteplase. RESULTS: In cases with guideline recommendations for alteplase, physicians favored alteplase in 82.0% under current local resources and in 79.3% under assumed ideal conditions (P < .001). Under assumed ideal conditions, interventional neuroradiologists would refrain from intravenous alteplase most often (6.28%, OR = 2.40; 95% CI, 1.01-5.71). When physicians' current and ideal decisions differed, most would like to add endovascular therapy to intravenous alteplase in an ideal setting (196/3861 responses, 5.1%). CONCLUSIONS: In patients eligible for endovascular therapy and intravenous alteplase, we observed a slightly lower decision rate in favor of intravenous alteplase under assumed ideal conditions compared with the decision rate under current local resources.

Imaging Triage of Patients with Late-Window (6-24 Hours) Acute Ischemic Stroke: A Comparative Study Using Multiphase CT Angiography versus CT Perfusion.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 (P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.