Advances in Prehospital Management of Intracerebral Hemorrhage.

BACKGROUND: Spontaneous acute intracerebral hemorrhage (ICH) is associated with greater stroke-related disability and mortality. Hematoma expansion (HME), an important treatment target in acute ICH, is time-dependent, with a greater probability of hematoma growth occurring <3 hours from ICH onset. SUMMARY: Promising treatment options to reduce HME include early intensive blood pressure (BP) reduction and the administration of hemostatic or anticoagulant reversal agents, yet large phase III clinical trials have so far failed to show overwhelming benefit for these interventions in acute ICH. Post-hoc analyses provide evidence, however, that the therapeutic benefit of such treatments is enhanced by rapid and ultra-early intervention, likely driven in large part by attenuation of early HME. Clinical trials assessing ultra-rapid treatments (<2 hours from ICH onset), including study procedures in the ambulance setting are currently underway, and demonstrate that the prehospital phase is a critical window for ICH management and an indispensable area of ICH research. Mobile stroke units, specialized ambulances equipped with imaging capabilities can provide confirmatory diagnosis and expedite treatments, as in acute ischemic stroke. Nevertheless, multiple barriers (financial, organisational, geographical among others) hinder worldwide implementation. Emerging portable technologies as well as point-of-care measures of blood biomarkers show promise as feasible adjunct tools to discriminate ICH from AIS in the field and have the potential for widespread accessibility. KEY MESSAGES: Ultra-early interventions in acute ICH are likely necessary to mitigate the risk of HME, and as such, the prehospital setting is ideal to initiate time-sensitive ICH therapies. As such, reliable prehospital acute ICH detection is essential to provide disease-specific treatments. Overall, it is imperative that "Time is brain" become the mantra not only for ischemic stroke but for ICH as well, and that the promise of ultra-early therapies for ICH be translated into concrete benefits for patients with this devastating condition.

Characteristics of Ischemic Stroke Despite Oral Anticoagulant Use For Atrial Fibrillation.

Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study.

BACKGROUND: Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion. METHODS: Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes. RESULTS: Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048). CONCLUSION: In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Non-contrast CT markers of intracerebral hematoma expansion: a reliability study.

OBJECTIVES: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion. METHODS: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC1, with a coefficient > 0.60 indicating substantial to almost perfect agreement. RESULTS: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker. CONCLUSION: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement. KEY POINTS: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC1> 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading).

Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT. METHODS: Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0-3 or equal to pre-stroke mRS at 3 months. RESULTS: Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36-0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83-0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32-10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08-0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization. CONCLUSIONS: Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Prospective Evaluation of a Two-Scale Protocol for Prehospital Large Vessel Occlusion Detection.

Background and purposes: Stroke severity scales may expedite prehospital large vessel occlusion (LVO) stroke detection, but few are validated for paramedic use. We evaluated the feasibility of introducing the Cincinnati Stroke Triage Assessment Tool (C-STAT) in the field and its capacity to detect LVO stroke.Methods: We performed a prospective paramedic-based study assessing C-STAT in the field on patients currently redirected to two comprehensive stroke centers (CSC), based on a Cincinnati Prehospital Stroke Scale (CPSS) score of 3/3. C-STAT was administered by on-site paramedics with telephone guidance from trained centralized clinical support paramedics.Results: Between October 2018 and November 2019, C-STAT scores were obtained in 188/218 (86.2%) patients, among which 118/188 (62.8%) were positive. Paramedics reported performing the C-STAT in less than 5 minutes on 170/188 (90.4%) patients and noted no difficulties administering the scale in 151/188 (80.3%). A positive C-STAT identified 51/68 (75%) LVO strokes in the cohort, demonstrating a 43% (95% CI: 38%-48%) positive and 76% (95% CI: 66%-83%) negative predictive value for LVO stroke diagnosis. In a cohort of 100 patients with CPSS 3/3, requiring a positive C-STAT for redirection would decrease CSC patient volume by 37 but miss 9 of 36 LVO strokes.Conclusion: Prehospital administration of the C-STAT was feasible, using a model of minimal paramedic training and real-time telephone guidance. A protocol based on both a CPSS 3/3 and a positive C-STAT would decrease CSC redirected patient volume by one-third but would miss one-quarter of LVO strokes when compared to a CPSS-based protocol.

Risk of Cancer Following an Ischemic Stroke in the Canadian Longitudinal Study on Aging.

BACKGROUND: Stroke survivors may be at higher risk of incident cancer, although the magnitude and the period at risk remain unclear. We conducted a retrospective cohort study to compare the risk of cancer in stroke survivors to that of the general population. METHODS: The Canadian Longitudinal Study on Aging is a large population-based cohort of individuals aged 45-85 years when recruited (2011-2015). We used data from the comprehensive subgroup (n = 30,097) to build a retrospective cohort with individual exact matching for age (1:4 ratio). We used Cox proportional hazards models to estimate hazard ratios of new cancer diagnosis with and without a prior stroke. RESULTS: We respectively included 920 and 3,680 individuals in the stroke and non-stroke groups. We observed a higher incidence of cancer in the first year after stroke that declined afterward (p-value = 0.030). The hazard of new cancer diagnosis after stroke was significantly increased (hazard ratio: 2.36; 95% CI: 1.21, 4.61; p-value = 0.012) as compared to age-matched non-stroke participants after adjustments. The most frequent primary cancers in the first year after stroke were prostate (n = 8, 57.1%) and melanoma (n = 2, 14.3%). CONCLUSIONS: The hazard of new cancer diagnosis in the first year after an ischemic stroke is about 2.4 times higher as compared to age-matched individuals without stroke after adjustments. Surveillance bias may explain a portion of post-stroke cancer diagnoses although a selection bias of healthier participants likely led to an underestimation of post-stroke cancer risk. Prospective studies are needed to confirm the potentially pressing need to screen for post-stroke cancer.

Three-month functional outcomes following endovascular thrombectomy during the first wave of the COVID-19 pandemic: a Canadian single-center cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted acute stroke care logistics, including delays in hyperacute management and decreased monitoring following endovascular therapy (EVT). We aimed to assess the impact of the pandemic on 90-day functional outcome among patients treated with EVT. METHODS: This is an observational cohort study including all patients evaluated for an acute stroke between March 30, 2020 and September 30, 2020 (pandemic cohort) and 2019 (reference cohort) in a high-volume Canadian academic stroke center. We collected baseline characteristics, acute reperfusion treatment and management metrics. For EVT-treated patients, we assessed the modified Rankin score (mRS) at 90 days. We evaluated the impact of the pandemic on a 90-day favourable functional status (defined as mRS 0-2) and death using multivariable logistic regressions. RESULTS: Among 383 and 339 patients included in the pandemic and reference cohorts, baseline characteristics were similar. Delays from symptom onset to evaluation and in-house treatment were longer during the early first wave, but returned to reference values in the subsequent months. Among the 127 and 136 EVT-treated patients in each respective cohort, favourable 90-day outcome occurred in 53/99 (53%) vs 52/109 (48%, p=0.40), whereas 22/99 (22%) and 28/109 (26%, p=0.56) patients died. In multivariable regressions, the pandemic period was not associated with 90-day favourable functional status (aOR 1.27, 95% CI 0.60 to 2.56) or death (aOR 0.74, 95% CI 0.33 to 1.63). CONCLUSION: In this single-center cohort study conducted in a Canadian pandemic epicenter, the first 6 months of the COVID-19 pandemic did not impact 90-day functional outcomes or death among EVT-treated patients.

Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial.

BACKGROUND: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial. METHODS: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days. RESULTS: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions. CONCLUSIONS: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).

Peri-hematoma corticospinal tract integrity in intracerebral hemorrhage patients: A diffusion-tensor imaging study.

BACKGROUND: The impact of perihematoma edema in Intracerebral Hemorrhage (ICH) on white matter integrity is uncertain. Fractional Anisotropy (FA), as measured with Diffusion Tensor Imaging (DTI), can be used to assess white matter microstructure. We tested the hypotheses that sections of the Corticospinal Tract (CST) passing through perihematoma edema would 1) have low FA relative to the contralateral CST and 2) would predict NIHSS motor score in ICH patients. METHODS: Patients were prospectively imaged with DTI at 48 h and 7 days after onset. Edema volume/extent was measured on CT at baseline and 24 h. FA, mean, axial and radial diffusivity were measured in the perihematoma edema, contralateral CST and sections of CST passing through the edema ('edematous CST'). RESULTS: Patients (n = 27, mean age 67 ± 13) were scanned with DTI at a median (IQR) of 42.3 (24.5) hours and 7.7 (1.8) days from onset. Median acute ICH volume was 8.8 (22) ml. FA in edematous CST at 72 h was decreased (0.37 ± 0.03) relative to contralateral CST (0.52 ± 0.06; p < 0.0001). Day 7 FA in edematous CST (0.35 ± 0.08) was also decreased compared to contralateral CST (0.54 ± 0.06; p < 0.0001). FA remained stable between 72 h (0.37 ± 0.03) and day 7 (0.35 ± 0.07; p = 0.350). FA at 72 h (ρ = -0.22, p = 0.420) and day 7 (ρ = -0.14, p = 0.624) was unrelated to 90-day motor score. CONCLUSIONS: FA is decreased in the CST where it passes through the edema. Decreased FA in the edematous CST remained stable over time, was unrelated to motor score, and may represent water infiltration into the tracts rather than axonal injury.

Antimicrobial activity of harzianic acid against Staphylococcus pseudintermedius.

The emerging concern about the increase of antibiotic resistance has encouraged research efforts to develop effective alternatives to counteract bacterial infections. Herein, we studied a new perspective to therapeutic treatment against Staphylococcus pseudintermedius, an opportunistic pathogen documented as the major cause of skin, ear, and post-operative bacterial infections in dogs and cats. Antimicrobial activity of secondary metabolites produced by selected microbial strains belonging to Trichoderma, Talaromyces, Clonostachys and Coniothyrium fungal genera has been tested against S. pseudintermedius. Several extracts, particularly those obtained from Trichoderma harzianum E45 and ET45, showed a significant antimicrobial activity towards S. pseudintermedius methicillin-resistant (MRSP) and methicillin-susceptible (MSSP) strains. Bioassay-guided fractionation of E45 and ET45 extracts allowed to isolate harzianic acid as the major compound responsible for biological activities (e.g. antimicrobial, antibiofilm formation and biofilm disaggregation).

Early Impact of the COVID-19 Pandemic on Acute Stroke Treatment Delays.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

Frequency and predictors of occult cancer in ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: The optimal approach for cancer screening after an ischemic stroke remains unclear. AIMS: We sought to summarize the existing evidence regarding the frequency and predictors of cancer after an ischemic stroke. SUMMARY OF REVIEW: We searched seven databases from January 1980 to September 2019 for articles reporting malignant tumors and myeloproliferative neoplasms diagnosed after an ischemic stroke (PROSPERO protocol: CRD42019132455). We screened 15,400 records and included 51 articles. The pooled cumulative incidence of cancer within one year after an ischemic stroke was 13.6 per thousand (95% confidence interval [CI], 5.6-24.8), higher in studies focusing on cryptogenic stroke (62.0 per thousand; 95% CI, 13.6-139.3 vs 9.6 per thousand; 95% CI, 4.0-17.3; p = 0.02) and those reporting cancer screening (39.2 per thousand; 95% CI, 16.4-70.6 vs 7.2 per thousand; 95% CI, 2.5-14.1; p = 0.003). Incidence of cancer after stroke was generally higher compared to people without stroke. Most cases were diagnosed within the first few months after stroke. Several predictors of cancer were identified, namely older age, smoking, and involvement of multiple vascular territories as well as elevated C-reactive protein and d-dimers. CONCLUSIONS: The frequency of incident cancer after an ischemic stroke is low, but higher in cryptogenic stroke and after cancer screening. Several predictors may increase the yield of cancer screening after an ischemic stroke. The pooled incidence of post-stroke cancer is likely underestimated, and larger studies with systematic assessment of cancer after stroke are needed to produce more precise and valid estimates.

Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Hemorrhage, 7th Edition Update 2020.

Spontaneous intracerebral hemorrhage is a particularly devastating type of stroke with greater morbidity and mortality compared with ischemic stroke and can account for half or more of all deaths from stroke. The seventh update of the Canadian Stroke Best Practice Recommendations includes a new stand-alone module on intracerebral hemorrhage, with a focus on elements of care that are unique or affect persons disproportionately relative to ischemic stroke. Prior to this edition, intracerebral hemorrhage was included in the Acute Stroke Management module and was limited to its management during the first 12 h. With the growing evidence on intracerebral hemorrhage, a separate module focused on this topic across the care continuum was added. In addition to topics related to initial clinical management, neuroimaging, blood pressure management, and surgical management, new sections have been introduced addressing topics surrounding inpatient complications such as venous thromboembolism, seizure management, and increased intracranial pressure, rehabilitation as well as issues related to secondary management including lifestyle management, maintaining a normal blood pressure and antithrombotic therapy, are addressed. The Canadian Stroke Best Practice Recommendations (CSBPR) are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and informal caregivers.

Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke.

OBJECTIVE: The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. PATIENTS AND METHODS: Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. RESULTS: The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5-49.3) ml in the NTG group and 32.6 (8.6-96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7-44.2) ml) than the NTG group (3.2 (0.5-16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. CONCLUSION: NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

Tecnologias não invasivas na assistência às parturientes de alto risco: percepções de enfermeiras obstétricas / Non-invasive technologies in assisting high-risk parturient women: nurse-midwives' perceptions

RESUMO Objetivo conhecer as percepções de enfermeiras obstétricas sobre os fatores relacionados com o uso das tecnologias não invasivas de cuidado na assistência às parturientes de alto risco. Métodos estudo qualitativo, com 10 enfermeiras obstétricas do centro obstétrico de uma maternidade de alto risco de um hospital universitário. Os dados foram coletados por meio de entrevistas semiestruturadas e submetidos à análise temática de conteúdo. Resultados a assistência pré-natal com o enfoque na autonomia feminina, a disponibilização de materiais específicos e a infraestrutura do setor são fatores facilitadores. A sobrecarga de trabalho, a desvalorização dos saberes das enfermeiras obstétricas por alguns profissionais médicos e a falta de apoio institucional ao trabalho em equipe são fatores limitadores. Conclusão os fatores referidos evidenciam a necessidade de impulsionar o trabalho colaborativo na assistência ao alto risco obstétrico, incentivar o uso das tecnologias não invasivas de cuidado e melhorar as condições laborais das enfermeiras.

ABSTRACT Objective to know nurse-midwives' perceptions about factors related with the use of non-invasive care technologies in the care of high-risk parturient women. Methods qualitative study, with 10 nurse-midwives from the obstetric center of a high-risk maternity hospital in a university hospital. Data were collected by semi-structured interviews and subjected to content analysis. Results prenatal care with a focus on female autonomy, the availability of specific materials and the sector's infrastructure are facilitating factors. Work overload, the devaluation of nurse-midwives' knowledge by some medical professionals and the lack of institutional support for teamwork are limiting factors. Conclusion the factors referred to show the need to boost collaborative work in assisting high obstetric risk, encourage the use of non-invasive care technologies and improve nurses' working conditions.