Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions.

BACKGROUND: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs. METHODS: Patient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0-2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality. RESULTS: Among 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46-117.5) mins vs 54 (21-100), P=0.607) and groin to recanalization time (59 (39.5-85.5) mins vs 54 (38-81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting. CONCLUSIONS: Our findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Association between intraprocedural drops in blood pressure and infarct growth rate patterns after acute large-vessel occlusions.

BACKGROUND: Infarct growth rate (IGR) differs among patients with acute ischemic stroke due to large vessel occlusion (LVO-AIS), and this variability has critical clinical repercussions. We explored IGR patterns and their association with blood pressure during endovascular therapy (EVT). METHODS: This is a two-center cohort observational study that included consecutive anterior circulation LVO-AIS patients who underwent EVT and achieved modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3. Initial and final infarct volumes (FIV) were defined using admission computed tomography perfusion (CTP) defined as relative cerebral blood flow (rCBF) <30%, and diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI) at 24 hours post-EVT. We categorized IGR patterns as exponential (ExpIGR) and Non-exponential (NonExp) based on their growth curves. We then dichotomized ExpIGR clinical significance based on the association of infarct growth with 90-day Modified Rankin Score (mRS) as ExpIGR-A (>13 mL) and ExpIGR-B (<13 mL). Intraprocedural blood pressure (BP) drops were calculated as the difference between median arterial pressure (MAP) at admission and the lowest intraprocedural MAP reading before recanalization, and the area between admission MAP threshold and all lower measurements of intraprocedural MAP. Logistic and linear regression were used to investigate associations between variables of interest. RESULTS: Of 159 modified Thrombolysis in Cerebral Infarction (mTICI) 2 c-3 patients, we found that 36% demonstrated ExpIGR-A, 31% ExpIGR-B, and 32.7% NonExp patterns. The Exp-A and Exp-B groups differed significantly in National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT Score (ASPECTS), glucose, and FIV. The Exp-A and NonExp groups differed in rCBF <30% vol, and time of stroke onset (SO) to admission CTP; and the Exp-B and NonExp groups in NIHSS, rCBF <30%, Tmax <6 s volume, collateral flow measured by hypoperfusion intensity ratio (HIR), and FIV. Hypotensive MAP area (HMA) was independently associated with an ExpIGR-A pattern. Infarct volume increased by 1 mL per 100 units of hypotensive area and 4.2 mL per 0.1 units of HIR, with a significant interaction between both variables. CONCLUSION: After an LVO-AIS, the IGR can be differentiated into two distinct exponential and non-exponential patterns. A subgroup of patients with the exponential pattern experienced clinically meaningful infarct growth rates between CTP acquisition and reperfusion and seem to be highly vulnerable to episodes of sustained intraprocedural BP drops during EVT.

Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes.

BACKGROUND AND PURPOSE: Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated. METHODS: Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death. RESULTS: We analyzed 255 patients with 210 baseline CTs, 255 24-hour CTs, and 81 72-hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ = -.22) and with CSF ratio and ΔCSF at 24 hours (ρ = -.55/.63) and 72 hours (ρ = -.66/.69), but not with NWU (ρ = .15/.25). Similarly, CSF ratio was correlated with RHV (ρ = -.69/-.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]: 1.95 per 0.1, 95% confidence interval [CI]: 1.52-2.59) and ΔCSF at 24 hours (OR: 1.87 per 10%, 95% CI: 1.47-2.49) were associated with malignant edema. CONCLUSION: CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake.

Functional and Safety Outcomes of Carotid Artery Stenting and Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke With Tandem Lesions.

Importance: Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear. Objective: To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs. Design, Setting, and Participants: This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography. Exposures: Patients with TLs were divided into CAS vs nonstenting groups. Main Outcomes and Measures: Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days. Results: Of 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P < .001) and atherosclerotic disease (296 [82.0%] vs 194 [74.6%], P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio [aOR], 1.67; 95% CI, 1.20-2.40; P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups. Conclusions and Relevance: In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Temporal profiles of systolic blood pressure variability and neurologic outcomes after endovascular thrombectomy.

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized. Patients and methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns. Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2-3.9; p = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT (p < 0.001). Discussion and conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV.

In vivo phenotyping of the microvasculature in necrotizing enterocolitis with multicontrast optical imaging.

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal emergency in premature infants and is characterized by a dysfunctional gut microcirculation. Therefore, there is a dire need for in vivo methods to characterize NEC-induced changes in the structure and function of the gut microcirculation, that is, its vascular phenotype. Since in vivo gut imaging methods are often slow and employ a single-contrast mechanism, we developed a rapid multicontrast imaging technique and a novel analyses pipeline for phenotyping the gut microcirculation. METHODS: Using an experimental NEC model, we acquired in vivo images of the gut microvasculature and blood flow over a 5000 × 7000 µm2 field of view at 5 µm resolution via the following two endogenous contrast mechanisms: intrinsic optical signals and laser speckles. Next, we transformed intestinal images into rectilinear "flat maps," and delineated 1A/V gut microvessels and their perfusion territories as "intestinal vascular units" (IVUs). Employing IVUs, we quantified and visualized NEC-induced changes to the gut vascular phenotype. RESULTS: In vivo imaging required 60-100 s per animal. Relative to the healthy gut, NEC intestines showed a significant overall decrease (i.e. 64-72%) in perfusion, accompanied by vasoconstriction (i.e. 9-12%) and a reduction in perfusion entropy (19%)within sections of the vascular bed. CONCLUSIONS: Multicontrast imaging coupled with IVU-based in vivo vascular phenotyping is a powerful new tool for elucidating NEC pathogenesis.

Midline Shift Greater than 3 mm Independently Predicts Outcome After Ischemic Stroke.

BACKGROUND: Cerebral edema is associated with worse outcome after acute stroke; however, the minimum clinically relevant threshold remains unknown. This study aimed to identify the minimal degree of midline shift (MLS) that predicts outcome in a cohort encompassing a broad range of patients with acute stroke. METHODS: Patient-level data from six acute stroke clinical trials were combined with endovascular thrombectomy registries from two academic referral centers, generating a combined cohort of 1977 patients. MLS was extracted from the original trial data or measured on computed tomography or magnetic resonance imaging that was obtained a median of 47.0 h (interquartile range 27.0-75.1 h) after stroke onset. Logistic regression was performed to identify predictors of poor outcome and the minimal clinically relevant MLS threshold. RESULTS: The presence of MLS was a predictor of poor outcome, independent of baseline clinical and demographic factors (adjusted odds ratio 4.46, 95% confidence interval 3.56-5.59, p < 0.001). Examining the full range of MLS values identified, a value of greater than 3 mm was the critical threshold that significantly predicted poor outcome (adjusted odds ratio 3.20 [1.31-7.82], p = 0.011). CONCLUSIONS: These results show that the presence of MLS predicts poor outcome and, specifically, MLS value greater than 3 mm is an important threshold across a variety of clinical settings. These findings may have relevance for the design and interpretation of future trials for antiedema therapies.

Telemedicine During the COVID-19 Pandemic: A Paradigm Shift in Non-Communicable Disease Management? - A Cross-Sectional Survey from a Quaternary-Care Center in South India.

PURPOSE: This study aims to gauge the perception and adoption rates of telemedicine amongst patients with non-communicable diseases (NCD) as opposed to in-person consultations in a quaternary care center in South India. PATIENTS AND METHODS: A web-hosted 21-item cross-sectional survey was distributed to 220 randomly selected patients with a routine appointment in one of the seven departments caring for NCDs in the study center. Descriptive analysis and inferential analyses were done. Paired samples T-test and Pearson's Chi-square test were used study associations. RESULTS: In-person consultations decreased by 1.9±4.47 visits per year, in 2020 vs 2019. Most participants reported "fear of COVID-19" as the primary reason for this decline. Participants also reported that their consultation times had significantly decreased (OR=6.43, 95% CI=1.7-24.08, p=0.006). The decreased consultations time, difficulty in obtaining in-person appointments, along with the reduced physical examination during consultations have made participants more open to the idea of teleconsultations (OR=3.88, 95% CI=1.21-12.47, p=0.022). Eighty-five (38.63%) participants had already adopted telemedicine for their routine consultations during the pandemic. Whilst participants felt that telemedicine was an adequate surrogate for in-person consultations, a significant difficulty in obtaining medications was noted (OR=6, 95% CI=1.34-26.81, p=0.019). CONCLUSION: In-person consultations were decreased primarily due to the perception of significant risk of COVID-19 exposure in the present scenario. Telemedicine adoption in the private sector may be sustainable throughout the pandemic and beyond, if patients are offered to continue their routine consultations with their regular doctors and ensured medicine availability. Integration of telemedicine by the public and private health sector of India into routine NCD care delivery is the need of the hour, but further studies are required to estimate the effectiveness of the systems.

HemoSYS: A Toolkit for Image-based Systems Biology of Tumor Hemodynamics.

Abnormal tumor hemodynamics are a critical determinant of a tumor's microenvironment (TME), and profoundly affect drug delivery, therapeutic efficacy and the emergence of drug and radio-resistance. Since multiple hemodynamic variables can simultaneously exhibit transient and spatiotemporally heterogeneous behavior, there is an exigent need for analysis tools that employ multiple variables to characterize the anomalous hemodynamics within the TME. To address this, we developed a new toolkit called HemoSYS for quantifying the hemodynamic landscape within angiogenic microenvironments. It employs multivariable time-series data such as in vivo tumor blood flow (BF), blood volume (BV) and intravascular oxygen saturation (Hbsat) acquired concurrently using a wide-field multicontrast optical imaging system. The HemoSYS toolkit consists of propagation, clustering, coupling, perturbation and Fourier analysis modules. We demonstrate the utility of each module for characterizing the in vivo hemodynamic landscape of an orthotropic breast cancer model. With HemoSYS, we successfully described: (i) the propagation dynamics of acute hypoxia; (ii) the initiation and dissolution of distinct hemodynamic niches; (iii) tumor blood flow regulation via local vasomotion; (iv) the hemodynamic response to a systemic perturbation with carbogen gas; and (v) frequency domain analysis of hemodynamic heterogeneity in the TME. HemoSYS (freely downloadable via the internet) enables vascular phenotyping from multicontrast in vivo optical imaging data. Its modular design also enables characterization of non-tumor hemodynamics (e.g. brain), other preclinical disease models (e.g. stroke), vascular-targeted therapeutics, and hemodynamic data from other imaging modalities (e.g. MRI).