In-vitro Wound Healing Assays: A Comprehensive Review.

Chronic non-healing wounds offer a tough clinical challenge for plastic and reconstructive surgeons. A systematic comprehension of the underlying mechanism of wound healing is essential for improved patient care. It is also required to know the complex and continuing armamentarium of therapeutic choices for treatment of chronic wounds. Wound assays are excellent way to apprehend the wound healing progression and the efficacy of various products that contribute and promote in wound healing. In the production sequence of wound care products also, human trials are often preceded by more economical in-vitro or preclinical studies. Wound healing assays are to understand the principal molecular mechanisms involved in repair progression and used in the exploration of impending therapeutics and designing treatment protocols intended for better curing. Several prototypes of wound healing have been established and are well-accepted. This review focuses on in vitro assays, as they are pre-requisite preliminary assays that are rapid, economical and ethical substitute to other complex assay models. Literature exploration for data sources were carried out through a meticulous search in indexed literature and various website centered educational research documents. In total 76 studies were earmarked from 286 most relevant scholarly articles. An extensive criterion to describe both in-vitro assays and in-vitro assays in wound healing has been used for probing the comments. Also, personal resources have been used for information gathering. The present manuscript provides a broad overview of various in-vitro assays with descriptive account of injury techniques with assessment of pros and cons of each. It also emphasized on three-dimensional culture assays, which utilizes bioengineered prototypes to exhibit various connections and the mechanisms of diverse sort of cells in the wound healing.

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.

Myocarditis post-SARS-CoV-2 vaccination: a systematic review.

Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (mean age: 25.5 ± 14.2 years) with most having taken an mRNA-based vaccine (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data were available for 1243 patients (56.9%), of whom 288 (23.2%) had reduced left ventricular ejection fraction. Non-steroidal antiinflammatory drugs (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data were available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment. The emergence of this adverse event calls for harmonizing case definitions and definite treatment guidelines, which require wider research.

ANTI-THYROID ANTIBODIES AND THE GONADOTROPHINS PROFILE (LH/FSH) IN EUTHYROID POLYCYSTIC OVARIAN SYNDROME WOMEN.

Context: The current study aimed to determine association of anti-TPO with LH/FSH in PCOS women. Design: Current case control study included 33 diagnosed PCOS women and 32 age matched healthy women and were analysed for body mass index (BMI) and waist to hip ratio (WHR), fasting blood glucose (FBG), free T3 (FT3), free T4 (FT4), Thyroid stimulating hormone (TSH), dehydroepiandrostenedione (DHEA-S), total testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and anti thyroperoxidase antibodies (anti-TPO). Data was statistically analysed by Student's t - test and Pearson's correlation analysis. Results: Of the total PCOS women, 45% were obese and 34.37% had raised anti-TPO. The biochemical profile of obese PCOS women showed significantly raised FBG (p<0.0001), LH (p<0.0001), Testosterone (p<0.0001) and DHEA-S (p=0.0021) as compared to non-obese PCOS women. The LH/FSH ratio was significantly raised in PCOS women as compared to control (p<0.0001). Pearson's correlation analysis showed a significant association of anti-TPO with FBS, testosterone, LH and LH/FSH in obese PCOS and with Testosterone and LH in non-obese PCOS women using SPSS 21. Conclusion: The current study shows a high prevalence of AITD in euthyroid PCOS women and suggests a strong link of euthyroid obese PCOS women to autoimmunity due to the hyper-anderogenism and a higher LH/FSH ratio.

Neuroimaging Findings in CHANTER Syndrome: A Case Series.

Recently, a distinct clinicoradiologic entity involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) on MR imaging was identified. Patients present in an unresponsive state following exposure to drugs of abuse. Very little information exists regarding this entity, particularly in the radiology literature. We identify and describe 3 patients at our institution with similar clinical and radiographic findings. Multifocal restricted diffusion in the brain is typically associated with poor outcomes. By contrast, CHANTER involves intraventricular obstructive hydrocephalus that, when treated, can lead to substantial recovery. This novel syndrome should be on the differential in patients who present in an unresponsive state after recent opioid use in the context of the above imaging findings. Additional diagnoses on the differential can include ischemic stroke, hypoxic-ischemic encephalopathy, "chasing the dragon," leukoencephalopathy, opioid-associated amnestic syndrome, and pediatric opioid-use-associated neurotoxicity with cerebellar edema.

Radiologic Evaluation Criteria for Chronic Subdural Hematomas: Recommendations for Clinical Trials.

Embolization of the middle meningeal artery has gained substantial interest as a therapy for chronic subdural hematomas. For the results of the currently running chronic subdural hematoma trials to inform clinical practice, sufficient accuracy and matching definitions are necessary. We summarized the current practice in chronic subdural hematoma evaluation and derived suggestions on reporting standards using the {Nested} Knowledge AutoLit living review platform. On the basis of the most commonly reported data elements, we suggested a set of standardized image-based study end points for chronic subdural hematoma evaluation for future trials. The measurement methods and reporting standards as proposed in this article have been derived from published best practices and are endorsed by the European Society of Minimally Invasive Neurological Therapy's research committee. The standardization of radiologic outcome measures and measurement techniques in chronic subdural hematoma embolization trials would increase the impact and implication of each trial as well as facilitate data pooling for increased statistical power and, therefore, translation to clinical practice.

Implementation of a Low-Field Portable MRI Scanner in a Resource-Constrained Environment: Our Experience in Malawi.

Low-field, portable MR imaging may expedite patient management in the setting of critical illness. We successfully implemented low-field MR imaging at the Queen Elizabeth Central Hospital in Malawi; a low-resource setting. We present our experience of low-field, portable MR imaging start-up and use in Malawi; the first of its kind in Sub-Saharan Africa, together with complementary troubleshooting mechanisms that may be used especially in similar resource-constrained contexts.

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.

Interrater Agreement and Detection Accuracy for Medium-Vessel Occlusions Using Single-Phase and Multiphase CT Angiography.

BACKGROUND AND PURPOSE: Accurate and reliable detection of medium-vessel occlusions is important to establish the diagnosis of acute ischemic stroke and initiate appropriate treatment with intravenous thrombolysis or endovascular thrombectomy. However, medium-vessel occlusions are often challenging to detect, especially for unexperienced readers. We aimed to evaluate the accuracy and interrater agreement of the detection of medium-vessel occlusions using single-phase and multiphase CTA. MATERIALS AND METHODS: Single-phase and multiphase CTA of 120 patients with acute ischemic stroke (20 with no occlusion, 44 with large-vessel occlusion, and 56 with medium-vessel occlusion in the anterior and posterior circulation) were assessed by 3 readers with varying levels of experience (session 1: single-phase CTA; session 2: multiphase CTA). Interrater agreement for occlusion type (large-vessel occlusion versus medium-vessel occlusion versus no occlusion) and for detailed occlusion sites was calculated using the Fleiss κ with 95% confidence intervals. Accuracy for the detection of medium-vessel occlusions was calculated for each reader using classification tables. RESULTS: Interrater agreement for occlusion type was moderate for single-phase CTA (κ = 0.58; 95% CI, 0.56-0.62) and almost perfect for multiphase CTA (κ = 0.81; 95% CI, 0.78-0.83). Interrater agreement for detailed occlusion sites was moderate for single-phase CTA (κ = 0.55; 95% CI, 0.53-0.56) and substantial for multiphase CTA (κ = 0.71; 95% CI, 0.67-0.74). On single-phase CTA, readers 1, 2, and 3 classified 33/56 (59%), 34/56 (61%), and 32/56 (57%) correctly as medium-vessel occlusions. On multiphase CTA, 48/56 (86%), 50/56 (89%), and 50/56 (89%) medium-vessel occlusions were classified correctly. CONCLUSIONS: Interrater agreement for medium-vessel occlusions is moderate when using single-phase CTA and almost perfect with multiphase CTA. Detection accuracy is substantially higher with multiphase CTA compared with single-phase CTA, suggesting that multiphase CTA might be a valuable tool for assessment of medium-vessel occlusion stroke.

Perceived Limits of Endovascular Treatment for Secondary Medium-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: Thrombus embolization during mechanical thrombectomy occurs in up to 9% of cases, making secondary medium vessel occlusions of particular interest to neurointerventionalists. We sought to gain insight into the current endovascular treatment approaches for secondary medium vessel occlusion stroke in an international case-based survey because there are currently no clear recommendations for endovascular treatment in these patients. MATERIALS AND METHODS: Survey participants were presented with 3 cases involving secondary medium vessel occlusions, each consisting of 3 case vignettes with changes in the patient's neurologic status (improvement, no change, unable to assess). Multivariable logistic regression analyses clustered by the respondent's identity were used to assess factors influencing the decision to treat. RESULTS: In total, 366 physicians (56 women, 308 men, 2 undisclosed) from 44 countries provided 3294 responses to 9 scenarios. Most (54.1%, 1782/3294) were in favor of endovascular treatment. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio = 2.62; 95% CI, 2.27-3.03) or A3 (59.7%; risk ratio = 2.11; 95% CI, 1.83-2.42) segment compared with the M3/4 segment (28.3%; reference). Physicians were less likely to pursue endovascular treatment in patients who showed neurologic improvement than in patients with an unchanged neurologic deficit (49.9% versus 57.0% responses in favor of endovascular treatment, respectively; risk ratio = 0.88, 95% CI, 0.83-0.92). Interventionalists and more experienced physicians were more likely to treat secondary medium vessel occlusions. CONCLUSIONS: Physicians' willingness to treat secondary medium vessel occlusions endovascularly is limited and varies per occlusion location and change in neurologic status. More evidence on the safety and efficacy of endovascular treatment for secondary medium vessel occlusion stroke is needed.

Use of office based transnasal oesophagoscopy in management of Head & Neck conditions during the COVID-19 pandemic at the Royal Albert Edward Infirmary, Wigan, United Kingdom.

OBJECTIVES: To assess the clinical and cost effectiveness of transnasal oesophagoscopy (TNO) in cases of suspected upper aerodigestive tract malignancy and define its role as a safe alternative to panendoscopy. We have also analysed if the implementation of TNO during the COVID-19 pandemic was beneficial in order to provide uninterrupted care to the patients with the limited resources available in these challenging times. METHODS: All patients who underwent TNO guided biopsies or dilatation attempted over a 7 month period during COVID- 19 pandemic were included by searching the hospital and department database at The Royal Albert Edward Infirmary. A comparative group of patients who underwent panendoscopy over 9 months were included for comparison. Demographic data, histological diagnosis, second procedure and cost involved were recorded. RESULTS: During this period, 20 TNO procedures (16 biopsies and 4 dilatations) were attempted which were compared with 20 panendoscopy procedures. The diagnostic accuracy of TNO biopsy for identifying benign and malignant pathology was 81.1%. The sensitivity and specificity for identifying malignancy was 76.9% and 100% respectively. The most common lesion location was laryngeal (43.8%) followed by oropharyngeal (37.5%), more specifically located at the tongue base. The median waiting period between the procedure being listed and TNO being performed was 5.5 days compared to 12 days for panendoscopy. There were 12/16 patients who did not require further interventions for histological diagnosis of the tumor. The TNO procedure was well tolerated with no complications and all were done under local anaesthesia as outpatient procedure without need for admission. TNO resulted in cost saving of £356 per case on a standard NHS tariff. CONCLUSION: TNO is a valuable diagnostic tool for patients with suspected UADT malignancy and dysphagia and has proven to be an asset during the COVID-19 pandemic when we have to make the best use of the limited theatre time and resources. Also, the cost analysis showed that outpatient based TNO can provide significant cost savings for the current standard of care. Furthermore, it has shown better patient tolerability, lesser complications and shortened the time for diagnosis and hence starting timely treatment for these patients.

MR Imaging Differences in the Circle of Willis between Healthy Children and Adults.

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.

Patient-Relevant Deficits Dictate Endovascular Thrombectomy Decision-Making in Patients with Low NIHSS Scores with Medium-Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: There is a paucity of evidence regarding the safety of endovascular treatment for patients with acute ischemic stroke due to primary medium-vessel occlusion. The aim of this study was to examine the willingness among stroke physicians to perform endovascular treatment in patients with mild-yet-disabling deficits due to medium-vessel occlusion. MATERIALS AND METHODS: In an international cross-sectional survey consisting of 7 primary medium-vessel occlusion case scenarios, participants were asked whether the presence of personally disabling deficits would influence their decision-making for endovascular treatment despite the patients having low NIHSS scores (<6). Decision rates were calculated on the basis of physician characteristics. Univariable logistic regression clustered by respondent and scenario identity was performed. RESULTS: Three hundred sixty-six participants from 44 countries provided 2562 answers to the 7 medium-vessel occlusion scenarios included in this study. In scenarios in which the deficit was relevant to the patient's profession, 56.9% of respondents opted to perform immediate endovascular treatment compared with 41.0% when no information regarding the patient's profession was provided (risk ratio = 1.39, P < .001). The largest effect sizes were seen for female participants (risk ratio = 1.68; 95% CI, 1.35-2.09), participants older than 60 years of age (risk ratio = 1.61; 95% CI, 1.23-2.10), those with more experience in neurointervention (risk ratio = 1.60; 95% CI, 1.24-2.06), and those who personally performed >100 endovascular treatments per year (risk ratio = 1.63; 95% CI, 1.22-2.17). CONCLUSIONS: The presence of a patient-relevant deficit in low-NIHSS acute ischemic stroke due to medium-vessel occlusion is an important factor for endovascular treatment decision-making. This may have relevance for the conduct and interpretation of low-NIHSS endovascular treatment in randomized trials.

Nonstenotic Carotid Plaques in Ischemic Stroke: Analysis of the STRATIS Registry.

BACKGROUND AND PURPOSE: Few studies assess nonstenotic carotid plaques on CTA, and the causative role of these plaques in stroke is not entirely clear. We used CTA to determine the prevalence of nonstenotic carotid plaques (<50%), plaque features, and their association with ipsilateral strokes in patients with cardioembolic and cryptogenic strokes. MATERIALS AND METHODS: Data were from the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry, a prospective, nonrandomized registry of patients undergoing thrombectomy with the Solitaire device. The prevalence of nonstenotic carotid plaques ipsilateral and contralateral to the stroke was compared in patients with cryptogenic and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Adjusted associations among nonstenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups were determined with logistic regression. RESULTS: Of the 946 patients in the data base, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with cryptogenic stroke (median age, 69 years) were included in the analysis. The prevalence of nonstenotic carotid plaque in the cardioembolic and cryptogenic subgroups was 33/226 (14.6%) and 32/141 (22.7%), respectively. Bilateral nonstenotic carotid plaques were seen in 10/226 (4.4%) patients with cardioembolic and 13/141 (9.2%) with cryptogenic strokes. Nonstenotic carotid plaques were significantly associated with ipsilateral strokes in the cardioembolic stroke (adjusted OR = 1.91; 95% CI, 1.15-3.18) and the cryptogenic stroke (adjusted OR = 1.69; 95% CI, 1.05-2.73) groups. Plaque irregularity, hypodensity, and per-millimeter increase in plaque thickness were significantly associated with ipsilateral stroke in the cryptogenic subgroup. CONCLUSIONS: Nonstenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and cryptogenic stroke groups, and there was an association of plaque irregularity and hypodense plaque with ipsilateral stroke in the cryptogenic group, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

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.

Infarct Growth despite Successful Endovascular Reperfusion in Acute Ischemic Stroke: A Meta-analysis.

BACKGROUND: Infarct volume inversely correlates with good recovery in stroke. The magnitude and predictors of infarct growth despite successful reperfusion via endovascular treatment are not known. PURPOSE: We aimed to summarize the extent of infarct growth in patients with acute stroke who achieved successful reperfusion (TICI 2b-3) after endovascular treatment. DATA SOURCES: We performed a systematic review and meta-analysis by searching MEDLINE and Google Scholar for articles published up to October 31, 2020. STUDY SELECTION: Studies of >10 patients reporting baseline and post-endovascular treatment infarct volumes on MR imaging were included. Only patients with TICI 2b-3 were included. We calculated infarct growth at a study level as the difference between baseline and follow-up MR imaging infarct volumes. DATA ANALYSIS: Our search yielded 345 studies, and we included 10 studies reporting on 973 patients having undergone endovascular treatment who achieved successful reperfusion. DATA SYNTHESIS: The mean baseline infarct volume was 19.5 mL, while the mean final infarct volume was 37.5 mL. A TICI 2b reperfusion grade was achieved in 24% of patients, and TICI 2c or 3 in 76%. The pooled mean infarct growth was 14.8 mL (95% CI, 7.9-21.7 mL). Meta-regression showed higher infarct growth in studies that reported higher baseline infarct volumes, higher rates of incomplete reperfusion (modified TICI 2b), and longer onset-to-reperfusion times. LIMITATIONS: Significant heterogeneity among studies was noted and might be driven by the difference in infarct growth between early- and late-treatment studies. CONCLUSIONS: These results suggest considerable infarct growth despite successful endovascular treatment reperfusion and call for a faster workflow and the need for specific therapies to limit infarct growth.

Clinical and Procedural Outcomes with or without Balloon Guide Catheters during Endovascular Thrombectomy in Acute Ischemic Stroke: A Systematic Review and Meta-analysis with First-line Technique Subgroup Analysis.

BACKGROUND: Balloon guide catheters are increasingly used to improve clot retrieval by temporarily stopping proximal blood flow during endovascular thrombectomy. PURPOSE: Our aim was to provide a summary of the literature comparing the procedural and clinical outcomes of endovascular thrombectomy with or without balloon guide catheters, depending on the first-line technique used. DATA SOURCES: We used PubMed/MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: We chose studies that compared using balloon guide catheters with not using them. DATA ANALYSIS: Random effects meta-analysis was performed to compare the procedural outcomes measured as the first-pass effect, successful reperfusion, number of passes, procedural duration, arterial puncture to reperfusion time, distal emboli, and clinical outcomes. DATA SYNTHESIS: Overall, a meta-analysis of 16 studies (5507 patients, 50.8% treated with balloon guide catheters and 49.2% without them) shows that the use of balloon guide catheters increases the odds of achieving a first-pass effect (OR = 1.92; 95% CI, 1.34-2.76; P < .001), successful reperfusion (OR = 1.85; 95% CI, 1.42-2.40; P < .001), and good functional outcome (OR =1.48; 95% CI, 1.27-1.73; P < .001). Balloon guide catheters reduce the number of passes (mean difference = -0.35; 95% CI, -0.65 to -0.04; P = .02), procedural time (mean difference = -19.73; 95% CI, -34.63 to -4.83; P = .009), incidence of distal or new territory emboli (OR = 0.5; 95% CI, 0.26-0.98; P = .04), and mortality (OR = 0.72; 95% CI, 0.62-0.85; P < .001). Similar benefits of balloon guide catheters are observed when the first-line technique was a stent retriever or contact aspiration, but not for a combined approach. LIMITATIONS: The analysis was based on nonrandomized trials with a moderate risk of bias. CONCLUSIONS: Current literature suggests improved clinical and procedural outcomes associated with the use of balloon guide catheters during endovascular thrombectomy, especially when using the first-line stent retriever.