Citations

Abstract Aims The incidence of respiratory failure and use of invasive or non-invasive mechanical ventilation (MV) in the cardiac intensive care units (CICUs) is increasing. While institutional MV volumes are associated with reduced mortality in medical and surgical ICUs, this volume–mortality relationship has not been characterized in the CICU. Methods and results National population-based data were used to identify patients admitted to CICUs (2005–2015) requiring MV in Canada. CICUs were categorized into low (≤100), intermediate (101–300), and high (>300) volume centres based on spline knots identified in the association between annual MV volume and mortality. Outcomes of interest included all-cause in-hospital mortality, the proportion of patients requiring prolonged MV (>96 h) and CICU length of stay (LOS). Among 47 173 CICU admissions requiring MV, 89.5% (42 200) required invasive MV. The median annual CICU MV volume was 43 (inter-hospital range 1–490). Compared to low-volume centres (35.9%), in-hospital mortality was lower in intermediate [29.2%, adjusted odds ratio (aOR) 0.84, 95% confidence interval (CI) 0.72–0.97, P = 0.019] and high-volume (18.2%; aOR 0.82, 95% CI 0.66–1.02, P = 0.076) centres. Prolonged MV was higher in low-volume (29.2%) compared to high-volume (14.8%, aOR 0.70, 95% CI 0.55–0.89, P = 0.003) and intermediate-volume (23.0%, aOR 0.85, 95% CI 0.68–1.06, P = 0.14] centres. Mortality and prolonged MV were lower in percutaneous coronary intervention (PCI)-capable and academic centres, but a shorter CICU LOS was observed only in subgroup of PCI-capable intermediate- and high-volume hospitals. Conclusions In a national dataset, we observed that higher CICU MV volumes were associated with lower incidence of in-hospital mortality, prolonged MV, and CICU LOS. Our data highlight the need for minimum MV volume benchmarks for CICUs caring for patients with respiratory failure.

Abstract The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance‐based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one‐way analysis of variance and post hoc paired student t‐test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT.

Introduction: Von Willebrand factor (VWF) is a key component of acute ischemic stroke (AIS) thrombi. The aim of our prospective study was to investigate the immunohistochemical expression of VWF in clots and to evaluate whether VWF is associated with certain subtypes of AIS. Methods: VWF immunostaining was performed on 79 thrombi collected as part of the multi-center Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) registry. The cases were classified according to TOAST criteria. The VWF expression was quantified using Orbit Image Analysis (www.Orbit.bio) machine learning software. IBM SPSS statistics 25 was used to assess the relationship between the VWF levels and different etiology subtypes. Results: A cardioembolic stroke was defined in 39 cases (49.4%) whereas an atherosclerotic origin was identified in 13 patients (16.5%). Other causes accounted for 12 cases (15.1%). Unknown etiology was reported in 15 cases (19%). The mean VWF content in the clots was 12.8%. According to the Mann-Whitney U-test, the level of VWF was significantly higher in the cases with unknown etiology compared to cardioembolic origin (p=0.044). We found also that patients with unknown etiology of stroke had higher VWF expression as compared to the other two subtypes, although this difference was not statistically significant. Conclusions: Among the patients with ischemic stroke included in this study, the VWF expression was significantly increased in those with unknown etiology compared to the group with cardioembolic stroke. Our finding provides new insights into clot composition in cryptogenic stroke and may influence the treatment and secondary prevention in these cases.

Introduction: Previous studies have successfully created blood clot analogues for In-vitro testing using animal blood. Blood components vary greatly among species and thus, creating clot analogues with human blood is likely a more accurate representation of thrombi formed in the human vasculature. We present a novel method of creating clot analogues from human blood and platelets that mimic the process by which clots form In-vivo . Methods: Following IRB approval from Mayo Clinic, human whole blood and platelets donations were obtained from the Blood Transfusion service. The whole blood was centrifuged at 1,200RPM for 20 minutes to separate it into its constituents. Plasma was removed and the remaining Red Blood Cells and Buffy Coat were mixed together by inverting. A total of 12 clot analogues were created with varying concentrations of components; Red Blood cells/Buffy Coat, Plasma and Platelets. Thrombin was added first to stimulate platelets activation for a total of 5 mins whilst continuously mixing by inversion. The RBC/WBC mixture was added next followed by CaCl2. The mixture was then quickly drawn into a 3cc syringe and spun overnight at 20RPM at room temperature to mimic dynamic flow conditions. Macro-photographs were taken to display the variation in texture and color between different clot analogue types. The clots were then fixed in 10% neutral buffered formalin for 24 hours prior to being processed. Histopathological analysis was performed using Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB) staining to confirm clot composition. Results: Red Blood cell-rich, Fibrin-rich, Platelet-rich and mixed clot analogues that accurately mimic clots retrieved from Acute Ischemic Stroke Patients were created. The range of histopathological compositions of the clot analogues is similar to that of the clinical samples. Conclusions: The addition and activation of platelets is key to creating accurate clot analogues for In-vitro testing. Spinning the clots is important to prevent natural sedimentation and mimic the In-vivo situation.

Ischemic stroke results from thrombus becoming lodged in a vessel in the cerebrovascular circulation. The constituents of the thrombus can vary widely and have direct effects on the mechanical properties of the thrombus. Thrombectomy procedures could potentially be improved if the mechanical properties of the thrombus could be determined prior to treatment. In the study, we developed a new non-contact method associated with Rayleigh wave propagations for evaluating mechanical properties of human clotted blood, referred to as ultrasound-mediated optical coherence elastography (UOCE). Due to clot mechanical properties being associated with fibrin and platelet content, eight different clot analogues with varying fibrin/platelets concentrations, from 0.6% (control group) to 19.0%, were produced, and the clot analog in each concentration was repeatedly measured five times. A highly focused transducer with a center frequency of 7.5 MHz was used to generate acoustic radiation forces exerted on the surface of clotted blood to induce Rayleigh wave propagations. The transducer was driven by a 50 dB radio frequency amplifier a 4 ms pulse which was repeated at a rate of 19 Hz. The optical coherence tomography (OCT) acquisition was set to 50 lateral positions and 4000 A-scans for each lateral position at a 76 kHz scan rate for total acquisition time of 52.6 ms. The results demonstrated that the Rayleigh wave group velocities positively correlated with the concentrations of fibrin/platelets. The group velocities ranged from 0.78 ± 0.02 m/s for 0.6% fibrin/platelets and increased to 2.42 ± 0.06 m/s at a fibrin/platelets concentration of 19.0%. There are statistically significant difference ( p <0.05) between control group and all clot analogues with a fibrin/platelets concentration of greater than 2.3%. In conclusion, we propose UOCE as a novel approach capable of evaluating mechanical properties of human blood clots based on Rayleigh wave propagation. This sensitive method can be used for the evaluation of the mechanical properties of human blood clot analogues and thrombectomy samples.

Introduction: Characterization of acute ischemic stroke thrombi has typically focused on the two dimensional (2D) histological characterization of the thrombus. Little is known about the three dimensional (3D) structure of these occlusive thrombi. Electron Microscopy (EM) can be used to obtain 3D information about the organization of clot components. Individual structures can be segmented and qualitative and quantitative information obtained from the clots. Methods: Following IRB approval from Mayo Clinic, acute ischemic stroke clot samples were collected from 10 patients treated at Mayo Clinic. Samples were immediately fixed in fresh modified Trumps fixative solution. A representative fragment of clot was taken and split longitudinally into two pieces; one piece was sent for 3D-EM analysis and the other for histological processing and analysis. Hematoxylin and eosin stain (H&E) and Martius Scarlett Blue (MSB) histological stains were used for conventional histopathology evaluation and components analysis. Immunohistochemical (IHC) staining using anti-CD42b (Platelets) was applied to confirm the presence of platelets in each clot. Serial block-face scanning electron microscopy was used to generate high-resolution three-dimensional images. Results: The 2D morphological features of the clot were identified using H&E, MSB and anti-CD42b staining. The 3D organization of thrombi varies greatly, both within and between clots depending on the constituents. Red Blood Cell-rich areas are mainly composed of Red Blood Cells packaged tightly together, with a small number of Fibrin strands interwoven between the cells. Fibrin-rich areas are characterized by dense networks of fibrin strands along with platelets and White Blood Cells with some sparse Red Blood Cells present. Platelet-rich areas are composed of large volumes of de-granulated platelets, some fibrin stands and white blood cells and an absence of Red Blood Cells. Conclusions: 3D electron microscopy can provide important information on the organization of components within thrombi. This could provide key information on the age and etiology of the thrombus. In addition, it may help to inform thrombolytic treatment and medical device design.

Background: We performed a multicenter prospective clinical registry across 11 centers to study the association between histopathological characteristics of retrieved clots and imaging, stroke etiology and clinical outcomes. Materials and Methods: Following IRB approval at the 11 centers, patients were enrolled in the STRIP registry. All retrieved emboli were sent for histopathological analysis with H&E and MSB staining. Demographic variables, comorbidities, stroke etiology, imaging findings and procedural details were collected for each case. We studied the association between clot histopathology and imaging findings, stroke etiology and and revascularization outcomes. Student’s t-test was used for continuous variables and chi-squared testing for categorical variables. Results: To date, 1022 patients have been included. There was a significant correlation between platelet rich clots and the absence of hyperdensity on non-contrast CT [p=0.321, p=0.003) and a significant inverse correlation between the percentage of platelets and mean HU on NCCT (p=-0.243, p=0.025). The proportion of platelet-rich clots (55.0% versus 21.2%, p=0.005) and the percentage of platelet content (22.1% versus 13.9%, p=0.03) was significantly higher in patient with large artery atherosclerosis compared to those with a cardioembolic etiology. There was no correlation between RBC density, WBC density, fibrin density or platelet density and revascularization outcomes with stent-retrievers. However, we have found that with aspiration alone, patients with platelet rich clots are less likely to be fully revascularized (i.e. TICI 2c/3) than non-platelet rich clots (OR=0.36, 95%CI=0.12-0.81, P<.0001). Meanwhile, patients with RBC rich clots are more likely to be completely revascularized with aspiration alone than those with RBC poor clots (OR=2.71, 95%CI=1.25-3.24, P=0.02). Conclusions: Interim analysis of the STRIP registry suggests that the platelet content of a clot may be the most revealing factor in determining a clot’s etiology, imaging features and revascularization outcome. Platelet rich clots are less dense on NCCT, are associated with a large artery atherosclerosis source and are less likely to be completely revascularized with aspiration alone.

Background The prevalence of excessive daytime sleepiness (EDS) in the general population is reported to be 9 to 28 percent. Various social and biological factors have been reported to contribute to the development of EDS, such as cardiovascular disease, metabolic disorders as well as socioeconomic status. Medically, EDS is associated with poorer prognosis in patients with sleep disorders. However, whether sleepiness is an independent negative prognostic indicator in patients without sleep apnea is poorly understood. Objective To evaluate the relationship between self‐reported excessive daytime sleepiness (assessed by Epworth Sleepiness Scale) and the risk of all‐cause mortality in patients without obstructive sleep apnea (OSA). Methods We performed a retrospective cohort study in a large registry of patients seen at the Mayo Clinic Center for Sleep Medicine between November 17 th , 2009 and April 15 th , 2017. All patients received a diagnostic polysomnography and had completed Epworth Sleepiness Scale (ESS). The primary outcome of all‐cause mortality risk was computed using the Kaplan‐Meier analysis and Cox‐proportional hazard model with age, sex, body mass index (BMI), baseline comorbidities and sleep measurements as confounders. Results A total of 2746 non‐OSA patients were identified. The overall median age (IQR) was computed as 53 (40, 63) with 45% of patients identifying as males. The median follow‐up time was approximately 2.3 years. In a univariate analysis, daytime sleepiness was associated with the female sex, younger age and higher BMI. No significant differences were observed in vascular related diseases between sleepy and non‐sleepy patients. EDS was not significantly associated with all‐cause mortality with an adjusted hazard ratio of 1.23 (95% CI 0.86, 1.76; p =0.257). In addition, there was no significant association of EDS and the risk of all‐cause mortality even after stratifying by sex, age and BMI in non‐OSA patients. Conclusion EDS is not associated with all‐cause mortality in non‐OSA patients. Further prospective studies are needed to confirm this finding. Support or Funding Information This research was supported by NIH HL65176 and NIH HL114024. Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. image Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

OBJECTIVE Scoliosis is common in patients with Chiari malformation type I (CM-I)–associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.