Atrial fibrillation is associated with higher first pass effect following thrombectomy for large vessel occlusion.

BACKGROUND: First pass effect (FPE), defined as single-pass complete or near complete reperfusion during endovascular thrombectomy (EVT) for large vessel occlusion (LVO) strokes, is a critical performance metric. Atrial fibrillation (AF)-related strokes have different clot composition compared with non-AF strokes, which may impact thrombectomy reperfusion results. We compared FPE rates in AF and non-AF stroke patients to evaluate if AF-related strokes had higher FPE rates. METHODS: We conducted a post-hoc analysis of the DIRECT-SAFE trial data, including patients with retrievable clots on the initial angiographic run. Patients were categorized into AF and non-AF groups. The primary outcome was the presence or absence of FPE (single-pass, single-device resulting in complete/near complete reperfusion) in AF and non-AF groups. We used multivariable logistic regression to examine the association between FPE and AF, adjusting for thrombolysis pre-thrombectomy and clot location. RESULTS: We included 253 patients (67 with AF, 186 without AF). AF patients were older (mean age: 74 years vs 67.5 years, p=0.001), had a higher proportion of females (55% vs 40%, p=0.044), and experienced more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) score: 17 vs 14, p=0.009) than non-AF patients. No differences were observed in thrombolytic agent usage, time metrics, or clot location. AF patients achieved a higher proportion of FPE compared with non-AF patients (55.22% vs 37.3%, adjusted odds ratio 2.00 (95% CI 1.13 to 3.55), p=0.017). CONCLUSIONS: AF-related strokes in LVO patients treated with EVT were associated with FPE. This highlights the need for preparedness for multiple passes and potential adjuvant/rescue therapy in non-AF-related strokes.

Differences in smoking behaviors and readiness to change for patients with COPD and differing categories of depressive symptoms: a descriptive cross-sectional design.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world with nearly 90% of cases caused by tobacco smoking. Nearly 40% of people with COPD are diagnosed with depression which impacts quality of life and smoking cessation. The purpose of this study was to describe factors influencing smoking behaviors and readiness to change in people with comorbid COPD and depression. METHODS: A descriptive cross-sectional design was used. A convenience sample of 222 participants self-reported and/or had a documented diagnosis of COPD. Participants completed study measures which included the PHQ-9 for depressive symptoms, assessment of smoking behaviors using The Cigarette Dependence Scale, report of readiness to change using The Smoking Stage of Change Questionnaire, The Smoking Decisional Balance Questionnaire, and The Processes of Change Questionnaire. Electronic and paper questionnaires were used. Data was stored in RedCap and analyzed using SPSS version 26. Based on variable type, descriptive and comparative analyses were conducted using ANOVA, t-test, chi-square, Pearson correlation, linear regression, and multiple linear regression to determine the relationships between smoking behaviors, COPD, and depressive symptoms. RESULTS: Only 18 participants were classified as having no depressive symptoms. Participants who smoked had high nicotine dependence and wanted to quit smoking. Overall, participants saw more cons to smoking and were engaged in the processes of change. The majority of participants were in the maintenance or contemplation stage. Cigarette dependence could decrease by 9% if depressive symptoms are treated. CONCLUSIONS: There is a need to assess COPD patients for depression and to assess COPD patients' smoking behaviors and readiness to change. Adequate treatment of depression could promote an individual to move through the stages of change from chronic contemplation to action, thus improving smoking cessation efforts for individuals with COPD. Understanding patients' smoking behaviors and readiness to change can aid in developing personalized interventions to achieve smoking cessation and improve long-term outcomes.

Early minimally invasive intracerebral hemorrhage evacuation: a phase 2a feasibility, safety, and promise of surgical efficacy study.

BACKGROUND: Surgical treatment of intracerebral hemorrhage (ICH) is unproven, although meta-analyses suggest that both early conventional surgery with craniotomy and minimally invasive surgery (MIS) may be beneficial. We aimed to demonstrate the safety, feasibility, and promise of efficacy of early MIS for ICH using the Aurora Surgiscope and Evacuator. METHODS: We performed a prospective, single arm, phase IIa Simon's two stage design study at two stroke centers (10 patients with supratentorial ICH volumes ≥20 mL and National Institutes of Health Stroke Scale (NIHSS) score of ≥6, and surgery commencing <12 hours after onset). Positive outcome was defined as ≥50% 24 hour ICH volume reduction, with the safety outcome lack of significant ICH reaccumulation. RESULTS: From December 2019 to July 2020, we enrolled 10 patients at two Australian Comprehensive Stroke Centers, median age 70 years (IQR 65-74), NIHSS score 19 (IQR 19-29), ICH volume 59 mL (IQR 25-77), at a median of 227 min (IQR 175-377) post-onset. MIS was commenced at a median time of 531 min (IQR 437-628) post-onset, had a median duration of 98 min (IQR 77-110), with a median immediate postoperative hematoma evacuation of 70% (IQR 67-80%). A positive outcome was achieved in 5/5 first stage patients and in 4/5 second stage patients. One patient developed significant 24 hour ICH reaccumulation; otherwise, 24 hour stability was observed (median reduction 71% (IQR 61-80), 5/9 patients <15 mL residual). Three patients died, unrelated to surgery. There were no surgical safety concerns. At 6 months, the median modified Rankin Scale score was 4 (IQR 3-6) with 30% achieving a score of 0-3. CONCLUSION: In this study, early ICH MIS using the Aurora Surgiscope and Evacuator appeared to be feasible and safe, warranting further exploration. TRIAL REGISTRATION NUMBER: ACTRN12619001748101.

Grassland songbird abundance is influenced more strongly by individual types of disturbances than cumulative disturbances associated with natural gas extraction.

Grassland birds have undergone widespread global population declines due to loss and degradation of native grasslands. Activities associated with non-renewable energy derived from oil and natural gas extraction have substantially increased on grasslands. The cumulative disturbance generated by natural gas development creates a network of non-linear (e.g., bare ground and exotic plant species) and linear (e.g., roads, trails, pipelines) features that may degrade habitat quality for grassland species. We quantified grassland songbird abundance in two areas of southwestern Saskatchewan, Canada, to determine whether variation in abundance 1) depended on the type and amount of disturbance at two spatial extents, and 2) was more affected by the cumulative impacts of natural gas development than any single type of disturbance. We found that specific types of disturbances impacted the abundance of most species to varying degrees. The cover of different types of linear disturbance had the strongest effect on the most species. Natural gas disturbance within 450 m of point counts was more influential than disturbance within 200 m for nearly all species in both areas. Only Savannah sparrow (Passerculus sandwichensis) abundance was most strongly influenced by the cumulative amount of disturbance with abundance decreasing with increased disturbance. Overall, we detected few consistent patterns among species, or within species between our two study areas. Our results indicated that the impact of natural gas infrastructure can extend beyond the local influences associated with well sites and that relatively small amounts of disturbance (<2%) may impact grassland songbird abundance. We recommend that researchers use caution when studying well-density effects or combining individual types of disturbance without understanding the separate effects each type of disturbance has on the species or community of interest. Not doing so may lead to investing resources into management practices that do not have the greatest possible benefit for grassland songbirds.

Implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer in a Radiation Oncology clinic.

PURPOSE: This article describes our experience in implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer. METHODS: Following the American Association of Physicists in Medicine Task Group-61 protocol, absolute output (absorbed dose to water at surface (cGy/min)) was measured for three energies (50, 70, and 100 kV) and for six applicators (1.5-5.0 cm in diameter). Percent depth dose (PDD) and profiles were also measured. Timer testing and ultrasound testing were performed. A treatment time calculation worksheet was created. Quality assurance (QA) of SRT-100 Vision was implemented. After treatment workflow for our clinic was developed, end-to-end (E2E) testing was performed using a Rando phantom. Considerations for treatment using SRT-100 Vision were made. RESULTS: Absolute output (cGy/min) decreases as energy increases and applicator size decreases. Due to scatter from the applicator, PDD at depths ≤5 mm does not follow conventional trends but PDD at depths ≥15 mm increases with increasing applicator size. Profiles for the 5 cm applicator do not have strong dependence on depth except profiles at 5 mm for 50 kV. Timer/end errors are negligible for all three energies. Ultrasound images confirm allowed field of view and depth as well as no image artifacts and spatial integrity. Daily, monthly and annual QA of SRT-100 Vision implemented in our clinic is listed in a table format. E2E testing results (<1%) demonstrate the functionality and performance of our treatment workflow. Our considerations for SRT treatment include patient, applicator size and energy selections, patient setup, and shields. CONCLUSIONS: This article is expected to serve as guidance for Radiation Oncology and/or Dermatology clinics aspiring to initiate an SRT program in their clinics.

Model to Inhibit Contraction in Third-Degree Burns Employing Split-Thickness Skin Graft and Administered Bone Marrow-Derived Stem Cells.

Third-degree burns typically result in pronounced scarring and contraction in superficial and deep tissues. Established techniques such as debridement and grafting provide benefit in the acute phase of burn therapy, nevertheless, scar and contraction remain a challenge in deep burns management. Our ambition is to evaluate the effectiveness of novel cell-based therapies, which can be implemented into the standard of care debridement and grafting procedures. Twenty-seven third-degree burn wounds were created on the dorsal area of Red Duroc pig. After 72 h, burns are surgically debrided using a Weck knife. Split-thickness skin grafts (STSGs) were then taken after debridement and placed on burn scars combined with bone marrow stem cells (BM-MSCs). Biopsy samples were taken on days 17, 21, and 45 posttreatment for evaluation. Histological analysis revealed that untreated control scars at 17 days are more raised than burns treated with STSGs alone and/or STSGs with BM-MSCs. Wounds treated with skin grafts plus BM-MSCs appeared thinner and longer, indicative of reduced contraction. qPCR revealed some elevation of α-SMA expression at day 21 and Collagen Iα2 in cells derived from wounds treated with skin grafts alone compared to wounds treated with STSGs + BM-MSCs. We observed a reduction level of TGFß-1 expression at days 17, 21, and 45 in cells derived from wounds treated compared to controls. These results, where the combined use of stem cells and skin grafts stimulate healing and reduce contraction following third-degree burn injury, have a potential as a novel therapy in the clinic.

Feasibility and acceptability of home delivery of water for dental caries control in Latinx children-"Sediento por una Sonrisa," Thirsty for a Smile: Single-arm feasibility study.

Background: Outcomes of surgical treatments under general anesthesia for early childhood caries of young children from low-income groups are poor requiring retreatment within 2 years. Dietary sugar is an ideal intervention target given that it is the most prominent risk factor for dental caries and there is increasing evidence of successful interventions to reduce its intake. Our aim is to investigate the feasibility and acceptability of the Thirsty for a Smile intervention, designed to promote consumption of water in lieu of sugar sweetened beverages, among children who underwent surgery for early childhood caries and their caregivers, mostly from Latino heritage. Methods: A single-arm feasibility study was conducted in a dental practice from a community health center in eastern Washington State. Bottled water was delivered to the participants' homes and caregivers received patient-centered counseling for setting goals to increase children's water intake and reduce sugar sweetened beverages consumption. We assessed the feasibility and acceptability of the intervention and study procedures through participation rates, interviews and a questionnaire completed by the caregivers. Data was analyzed and themes and descriptive statistics presented. Results: Twenty-two dyads of caregivers and their children between 2 and 9 years old who recently had surgical treatment for early childhood dental caries were enrolled. All study assessments were completed by more than 90% of participants, except for the final 24-h dietary recall (73%). Dietary counseling, both in person and brief telephone calls, was highly acceptable to the caregivers, and they also reported their children enjoyed and used the water bottles. On a scale from 1 to 10, the average rating for the helpfulness of the dietary counseling component for changing child's drinking habits was 9.62 and for the water delivery component, 8.86. Conclusions: This study tested the feasibility of conducting a trial in a dental practice setting, and the acceptability among caregivers of young children who underwent surgery for early childhood caries. It demonstrated that the Thirsty for a Smile intervention and study processes were feasible and acceptable. The study provides useful information for implementation of a two-arm randomized controlled trial in this setting and may also benefit other researchers attempting to test similar interventions.

Formation of polycyclic aromatic hydrocarbons and regulated emissions from biodiesel and n-butanol blends containing water.

To increase the use of biofuels in diesel engines and reduce harmful emissions emitted from diesel fuel, biodiesel and higher alcohols are fuel sources at the forefront of research. The aim of this study is to understand the effect of water-containing n-butanol-biodiesel blends on regulated emissions, emphasizing nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs), which are harmful for the environment and engine durability. 10% n-butanol (B90Bu10) and 10% n-butanol-1% water (B89Bu10W1) were blended with 89% waste-oil biodiesel and tested in a diesel engine at four engine loads at a constant engine speed. PAH samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Results showed B100, B90Bu10 and B89Bu10W1 blends increased break specific fuel consumption (BSFC), exhaust gas temperatures (EGT), carbon monoxide (CO) and hydrocarbon (HC) emissions. However, NOx emissions significantly decreased using butanol and butanol-water blends. Compared to diesel, biodiesel and blended fuels significantly reduced total PAHs and PAH toxicity up to 75.0%. However, B89Bu10W1 increased total PAH and PAH toxicity by 35.7%. Overall, the biodiesel-butanol blend, which emits less carcinogenic pollutants and low-cyclic PAHs than water-containing fuel, was found to reduce the risk of wetstacking in diesel engines operating under low loads.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Screening for phenotypic outliers identifies an unusually low concentration of a ß-lactoglobulin B protein isoform in bovine milk caused by a synonymous SNP.

BACKGROUND: Milk samples from 10,641 dairy cattle were screened by a mass spectrometry method for extreme concentrations of the A or B isoforms of the whey protein, ß-lactoglobulin (BLG), to identify causative genetic variation driving changes in BLG concentration. RESULTS: A cohort of cows, from a single sire family, was identified that produced milk containing a low concentration of the BLG B protein isoform. A genome-wide association study (GWAS) of BLG B protein isoform concentration in milk from AB heterozygous cows, detected a group of highly significant single nucleotide polymorphisms (SNPs) within or close to the BLG gene. Among these was a synonymous G/A variation at position + 78 bp in exon 1 of the BLG gene (chr11:103256256G > A). The effect of the A allele of this SNP (which we named B') on BLG expression was evaluated in a luciferase reporter assay in transfected CHO-K1 and MCF-7 cells. In both cell types, the presence of the B' allele in a plasmid containing the bovine BLG gene from -922 to + 898 bp (relative to the transcription initiation site) resulted in a 60% relative reduction in mRNA expression, compared to the plasmid containing the wild-type B sequence allele. Examination of a mammary RNAseq dataset (n = 391) identified 14 heterozygous carriers of the B' allele which were homozygous for the BLG B protein isoform (BB'). The level of expression of the BLG B' allele was 41.9 ± 1.0% of that of the wild-type BLG B allele. Milk samples from three cows, homozygous for the A allele at chr11:103,256,256 (B'B'), were analysed (HPLC) and showed BLG concentrations of 1.04, 1.26 and 1.83 g/L relative to a mean of 4.84 g/L in milk from 16 herd contemporaries of mixed (A and B) BLG genotypes. The mechanism by which B' downregulates milk BLG concentration remains to be determined. CONCLUSIONS: High-throughput screening and identification of outliers, enabled the discovery of a synonymous G > A mutation in exon 1 of the B allele of the BLG gene (B'), which reduced the milk concentration of ß-lactoglobulin B protein isoform, by more than 50%. Milk from cows carrying the B' allele is expected to have improved processing characteristics, particularly for cheese-making.

Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial.

Background: Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed. Aims: We sought to evaluate the effect of TXA on IVH growth. Methods: We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5 h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1 mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6 mL or 33%), and revised definitions of hematoma expansion (> 6 mL or 33% or IVH expansion ≥ 1 mL, > 6 mL or 33%, or any IVH expansion, and > 6 mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume. Results: The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13-1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28-1.66]). IVH growth ≥ 1 mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo. Conclusions: IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further. Registration: http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Systematic evaluation and plan quality assessment of the Leksell® gamma knife® lightning dose optimizer.

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation.

Efficacy and Safety of Locally Injected Tranexamic Acid in Hip Fracture Patients: A Retrospective Review.

OBJECTIVE: To determine whether locally injected tranexamic acid (TXA) used in the surgical treatment of fragility hip fractures can lower transfusion rates without increasing the risk of complications. DESIGN: Retrospective comparative cohort. SETTING: Tertiary referral orthopaedic specialty hospital, Level I trauma center. PATIENTS/PARTICIPANTS: A total of 490 patients (252 patients received TXA) 50 years of age and older who underwent surgery for a low-energy fragility fracture of the proximal femur between March 2018 and February 2020 were included in this study. INTERVENTION: Use of locally injected TXA at the time of wound closure. MAIN OUTCOME: The main outcomes of this study were the number of patients requiring postoperative blood transfusions, incidences of venous thromboembolism, and surgical site infections. RESULTS: A statistically significant difference was noted in the frequency of transfusion between patients who received TXA compared with those who did not receive TXA (33% vs. 43%, respectively) (P = 0.034). There were no significant differences in venous thromboembolism incidence (0.4% vs. 0.8% TXA vs. No TXA) (P = 0.526) or infections (0.4% vs. 0.4% TXA vs. No TXA) (P = 0.965). Regression analysis indicated that the use of TXA reduced the need for postoperative blood transfusion by 31% (odds ratio: 0.688, 95% CI: 0.477-0.993, P = 0.045). CONCLUSION: Locally injected TXA significantly reduced the need for postoperative transfusion in the surgical treatment of fragility hip fractures. In addition, there was no increased risk of complications in those receiving TXA versus those who did not. Locally injected TXA seems to be both a safe and effective way to reduce postoperative blood transfusions in patients with fragility hip fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Does variability in automated perfusion software outputs for acute ischemic stroke matter? Reanalysis of EXTEND perfusion imaging.

AIMS: We reprocessed the Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) perfusion imaging with a different automated software with the aim of comparing mismatch eligibility and outcomes. METHODS: EXTEND baseline perfusion imaging data were reprocessed using autoMIStar software to identify patients who were eligible based on the same target mismatch criteria as per the original trial. RESULTS: From the 225 patients fulfilling RAPID-based mismatch criteria randomized in the EXTEND study, 196 (87%) patients met the revised mismatch criteria. Most common reasons for not meeting revised criteria were core >70 ml (n = 9), and no perfusion lesion/lack of penumbral tissue (n = 20). The revised perfusion lesion volumes were significantly smaller compared to the original RAPID volumes (median 68 ml IQR 34-102 ml vs. 42 ml 16-92 ml, p = 0.036). Of the patients who met the revised mismatch criteria, 40% receiving alteplase had modified Rankin Scale (mRS) 0-1 at 3-month compared to 28% with placebo (Adjusted Odds Ratio (OR) = 2.23, CI 1.08-4.58, p = 0.028). In contrast, in the original mismatch cohort, 35% receiving alteplase had mRS 0-1 at 3-month compared to 30% with placebo (adjusted OR = 1.88, p = 0.056). CONCLUSIONS: These data reinforce the benefit of alteplase in the later time window, and suggest that differences in automated perfusion imaging software outputs may be clinically relevant.

Impact of MRI timing on tumor volume and anatomic displacement for brain metastases undergoing stereotactic radiosurgery.

BACKGROUND: The objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM). METHODS: Consecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning). RESULTS: 101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001). CONCLUSIONS: Changes in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.

Effect of Mechanical Debridement and Irrigation With Hypochlorous Acid Wound Management Solution on Methicillin-resistant Staphylococcus aureus Contamination and Healing Deep Dermal Wounds in a Porcine Model.

BACKGROUND: Wound cleansing is an important component of wound management. PURPOSE: This study was conducted to examine the effect of a wound management solution (WMS) containing hypochlorous acid (HOCl) on methicillin-resistant Staphylococcus aureus (MRSA) and healing when used in conjunction with debridement. METHODS: Nineteen (19) deep reticular dermal wounds (22 mm × 22 mm × 3 mm deep) were created on the paravertebral and thoracic areas of 3 female pigs using a specialized electrokeratome. Wounds were separated by at least 5 cm to 7 cm of unwounded skin and inoculated with MRSA. After 72 hours, all wounds were debrided with a curette and irrigated with either the WMS or sterile saline solution twice per day from day 0 to day 4. Wounds then were irrigated once a day until the completion of the study (day 11). Wound tissue specimens were taken using punch biopsy for microbiological and histological analysis on days 4, 8, and 11 post treatment. Percent of wound epithelialized, epithelial thickness (cell layers µm), white cell infiltrate (1 = absent, 2 = mild, 3 = moderate, 4 = marked, 5 = exuberant), and percent of granulation tissue formation were calculated and assessed. Microbiology and histology results were analyzed for significant differences between treatments and among assessment days using one-way analysis of variance and student t-tests. A P value ≤ .05 was considered significant. RESULTS: The WMS effected a bacterial reduction (P ≤ .05) of more than 2.74 ± 0.43 and 1.03 ± 0.22 Log CFU/g in all assessment days compared with baseline before and after debridement, respectively. Percent epithelialization was significantly different between treatments on day 8, only 78.3% and 67.8% for HOCl and saline, respectively (P ≤ .05). No significant differences between treatments were observed for epithelial thickness or granulation tissue formation. CONCLUSION: The combination of debridement and HOCl wound irrigation can significantly reduce MRSA contamination and facilitate the healing process compared to saline irrigation. Clinical studies are needed to confirm these results.

Update on the effects of GLP-1 receptor agonists for the treatment of polycystic ovary syndrome.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) offer a unique opportunity to simultaneously address various comorbid associated conditions and phenotypic presentations of polycystic ovary syndrome (PCOS) as these agents improve insulin sensitivity, reduce cardiovascular disease (CVD) risk, result in weight loss, and improve nonalcoholic fatty liver disease.Areas covered: The authors describe trials conducted during the last 5 years and provide an update on exenatide and liraglutide use in PCOS women. Information from the studies investigating GLP-1 RAs effects on reducing CVD risk in PCOS is also presented.Expert opinion: Exenatide and liraglutide are good options for the treatment of PCOS when used alone or in combination with metformin. Especially strong consideration should be given to GLP-1 RAs when developing treatment strategies for PCOS women who are overweight or obese, glucose intolerant, have CVD or its attendant risk factors, and/or are seeking treatment for infertility.

Effects of anti-diabetic treatments in type 2 diabetes and fatty liver disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are significant non-communicable diseases that often affect individuals concurrently. In individuals with both T2DM and NAFLD, there is evidence that anti-diabetic therapies may demonstrate potential combined beneficial metabolic and reduced hepatic inflammatory effects.Areas covered: A PubMed and Google Scholar search was performed to find relevant literature. Included studies focused on individuals with T2DM and NAFLD receiving anti-diabetic treatments including bariatric surgery, insulin sensitizers, incretin mimetics, and SGLT2 inhibitors. Additional articles highlight investigational treatments.Expert opinion: In individuals with T2DM and NAFLD, 5-10% weight loss or bariatric surgery if unable to lose weight or maintain weight loss are appropriate. GLP-1 receptor agonists and SGLT2 inhibitors result in weight loss, appear safe and may provide beneficial hepatic outcomes. Whether their effects are related to favorable weight changes or intrinsic hepatic effects is unclear. Thiazolidinediones have advantageous anti-hyperglycemic and hepatic effects but individuals must be monitored for weight gain and edema. Metformin and DPP-4 inhibitor beneficial hepatic effects remain debated. There are opportunities to standardize markers and imaging of NAFLD. Studies powered to evaluate the possible cardiovascular benefits of anti-diabetic therapies in individuals with T2DM and NAFLD are needed.

Localized Versus Generalized Granuloma Annulare: A Retrospective Review of 407 Patients.

BACKGROUND: Granuloma annulare has been linked to diabetes, dyslipidemia, thyroid disease, collagen vascular disease, malignancies, infectious hepatitis, and systemic infections. However, these associations have not been systematically investigated when categorized by its clinical variants. OBJECTIVE: To evaluate disease associations of localized and generalized granuloma annulare. METHODS: In total, 407 granuloma annulare patients from 1989 to 2019 were retrospectively reviewed, categorized by clinical variant (localized or generalized), age (pediatric or adult), and diagnostic method (clinical or histologic). Descriptive statistical analyses and multivariate logistic regression analysis were performed. Fisher's exact tests were conducted to produce unbiased probability values. RESULTS: Overall, 75.2% of the study sample was female, 47.2% had dyslipidemia, 24.8% were diabetic, and 24.6% had thyroid disease. Dyslipidemia (OR 2.15, CI 1.95-2.35, P < .001), diabetes (OR 1.16, CI 1.01-1.31, P = .041), and histologic diagnosis (OR 2.08, CI 1.21-3.52, P = .007) were associated with increased risk of GGA compared to LGA. When stratified by adult versus pediatric cases, dyslipidemia and diagnostic method remained significant, but diabetes did not. CONCLUSIONS: Evaluating granuloma annulare by its clinical variants may help to determine disease associations with each variant.

Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy: ACT-FAST Validation Study.

BACKGROUND AND PURPOSE: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm. METHODS: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening. RESULTS: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0-61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region. CONCLUSIONS: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.