bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 210: A Phase I Clinical Trial of Sildenafil for the Treatment of Cerebral Vasospasm Following Subarachnoid Hemorrhage
Authors: Washington Chad W , Dhar Rjat , Derdeyn Colin , Zipfel Gregory 
Published: March 2022

Introduction:
Animal studies have indicated that phosophodiesterase V (PDE-V) inhibition reduces cerebral vasospasm and improves outcomes following subarachnoid hemorrhage (SAH).

Hypothesis:
We hypothesize that sildenafil (an FDA-approved PDE-V inhibitor) is safe when given to patients with aneurysmal SAH and improves cerebral vasospasm.

Methods:
A prospective, non-randomized proof-of-principle trial using a two-phase dose escalation scheme was implemented. Patients with SAH underwent day-7 screening angiography to assess for vasospasm. In phase I, those with moderate to severe vasospasm were given 10mg (low dose) of intravenous sildenafil, followed by repeat angiography 30 mins after infusion. In phase II, patients with any degree of vasospasm were given 30mg (high dose) of sildenafil, followed by repeat angiography.

Safety was assessed by analyzing vital signs, intracranial pressure (ICP) monitoring neurological status, and observing for the development of adverse reactions attributable to sildenafil.
Two blinded reviewers compared pre- and post-sildenafil angiographic images to admission angiography and subjectively graded them as “improvement” or “no improvement” in vasospasm. Unblinded quantitative measurements of vessel diameter change were also made between pre- and post-sildenafil angiograms.

Results:
Eleven of 23 patients enrolled had vasospasm, received sildenafil and underwent repeat angiography (5 received the 10mg dose and 6 the 30mg dose).

There were no adverse effects upon heart rate, ICP, or neurologic status. Sildenafil infusion did result in a transient decline in mean arterial pressure (MAP). With the low dose there was a 16% decline in MAP with an average time to return to baseline of 16 mins. For the high dose the decline was 19% with an average of 33 mins to return to baseline.
Seven of 11 (64%) had angiographic improvement in vasospasm, with 3 of 5 (60%) from the low dose group and 4 of 6 (67%) from the high dose group. The average vessel dilatation in responders was 1.25 mm.

Conclusions:
Sildenafil is safe and well tolerated when given for the acute treatment of SAH-related cerebral vasospasm. These findings provide preliminary evidence that angiograpic vasospasm is improved in select patients following sildenafil infusion.
Abstract T P1: Higher Recanalization Rate with Stentrievers, but Outcome Not Improved
Authors: Simonsen Claus Z , Sørensen Leif H , Karabegovic Sanja , Juul Niels , Andersen Grethe 
Published: March 2022

Introduction:
Intraveneous (iv) recombinant tissue plasminogen activator (tPA) is the evidence based treatment in acute stroke. Intraarterial treatment with tPA and/or instrumentation of the vessel with the attempt to manipulate the clot and remove it (called Intra Arterial Therapy (IAT)) is emerging as a tool for treating patients with contraindications to iv tPA or for patients with large clot burden, where iv tPA is often unsuccessful. IAT has been shown to have better recanalization rates than iv tPA (1), but in a randomized trial, IAT did not prove itself better than traditional iv tPA (2). Stentrievers (ST) are a new form of removable stent and it has shown promise in improving recanalization and outcome in IAT (3).

Materials and methods:
At our institution, 237 patients underwent IAT from 2004-2012. STs were used as part of the recanalization procedure in 92 patients.

Results:
Recanalization (defined as TICI 2b or 3) was achieved among 76 of the 92 patients=83 % in the ST group and in 61/145=42 % of the patients in the non-ST group, giving an odds ratio (OR) for recanalization using ST on 6.54 (p<0.0001). Good outcome defined as a modified Rankin Score (mRS) of 0-2 90 days after the stroke was achieved among 44/92=48% in the ST group and among 63/145=43% in the non-ST group. There was no statistical difference between these rates.

Univariate analysis showed no differences in demographic data between ST and non-ST groups: Mean age 68 vs. 67 years (p=0.37), mean presenting NIHSS 17 vs. 16 (p=0.07) and time to groin puncture was 235 minutes in the ST group and 240 minutes in the non-ST group (p=0.17) (Mann-Whitney test).

Conclusion:
Recanalization is important for good outcome, but even though recanalization was achieved much more often in the ST group, this did not translate into better outcomes. Our findings are in line with the SWIFT study (3) where outcome defined as mRS 0-2 after 90 days were also not different between the ST group and the MERCI group. Manipulating the clot with the risk of distal embolization has been speculated to offset the benefit of recanalization (4).

References:
1) Stroke 2007;38:967-973

2) NEJM 2013;368:893-903
3) Lancet 2012;380:1241-1249
4) Stroke 2013;44:1761-1764
Abstract T P116: Increased Maintenance of Motor Gains Following a Novel Stroke Therapy
Authors: Falcon M. I , Riley Jeffrey D , Chen E. E , Solodkin Ana 
Published: March 2022

Introduction:
Action observation therapy (AOT), a novel approach based on the physiology of the mirror neuron system, uses observation/imitation of movements to facilitate recovery from stroke. We previously showed that AOT confers significant improvement in motor performance. More importantly, these gains are maintained up to 1 year compared to a classic therapy, ND Bobath (NDBT) (Falcon et al 2013). In this study we sought to determine concomitant brain function associated with motor recovery after these therapies and with maintenance of motor gains.

Methods:
Seventeen stroke subjects received either AOT or NDBT for 2 hours/day for 4 weeks. Motor outcome measures and MRI (T1-weighted and fMRI during a bimanual motor task) were acquired pre-treatment (Pre-Tr), post-treatment (Post-Tr) and maintenance after 6-12 months (MiNT). MRI data was processed in AFNI using a general linear model. Network analysis assessing effective connectivity was done via structural equation models (SEM). MRI from 20 healthy controls was included.

Results:

1. fMRI:
Pre-Tr: Compared to controls, all stroke subjects showed increased activation, mainly in parietal and frontal regions.
Post-Tr: Activation decreased in these regions in all stroke subjects.
MiNT: Activation was further decreased in the AOT group, while the NDBT group showed increased activity reminiscent of Pre-Tr levels.
2. SEM:
Pre-Tr: Both group networks involved nodes in parietal and frontal regions with strong connections in both hemispheres.
Post-tr: The weight of connections in the non-dominant hemisphere after AOT decreased compared to Pre-Tr levels. After NDBT, it increased.
MiNT: The weight of connections in the non-dominant hemisphere after AOT continued to decrease.

Conclusions:
Although decreased brain activation in both groups was associated with better motor performance Post-Tr, brain connectivity was discordant; effective connectivity decreased after AOT and increased after NDBT. This indicates differing mechanisms associated with stable (gains maintained) and poor (gains lost) recovery after AOT and NDBT respectively. These results may highlight relevant functional mechanisms for developing potential therapies.
Abstract T P234: Cell Cycle Inhibition via Blocking Src Family Kinases Promotes Hippocampal Neuron Survival and Improves Cognitive Function after Intraventricular Hemorrhage
Authors: Liu DaZhi , Ander Bradley P , Van Ken , Izadi Ali , Zhan Xinhua , Stamova Boryana , Jickling Glen C , Berman Robert F , Lyeth Bruce G , Sharp Frank R 
Published: March 2022

Intraventricular hemorrhage (IVH) is one of the most serious hemorrhagic brain diseases being associated with blood brain barrier (BBB) disruption, brain edema, neuron loss, cognitive impairment and high mortality in humans. Increasing evidence suggests that neuronal cell death ensues when neurons attempt to re-enter the cell cycle. Our previous study has demonstrated that cell cycle inhibition via blocking Src family kinases (SFKs) prevents neuronal cell death. However, one of the concerns with cell cycle therapy might be that it would inhibit proliferation of neural progenitor cells (NPCs) and that inhibiting neurogenesis would produce cognitive effects related to the therapy itself.
Using the rodent in vivo IVH model we show that i.p. injection of SFK inhibitor (PP2) prevents IVH-induced death of hippocampal neurons and cognitive deficits assessed on the Morris Water Maze. Moreover, PP2 (i.p.) alone did not affect proliferation of NPCs and did not affect cognition. Since there are several SFK gene family members in brain, we targeted specific SFK subtypes (e.g. Fyn, Lck and c-Src) using a newly developed in vivo nanoparticle-based siRNA transfection system. We show that nanoparticle-siRNA-Fyn plus nanoparticle-siRNA-Src attenuate IVH-induced neuron loss and cognitive deficits. Nanoparticle-siRNA-Fyn nor nanoparticle-siRNA-Src had no significant affects on population of NPCs or cognitive side effects, possibly because the nanoparticle-based siRNA transfection system only produces transient knockdown of the gene targets. This could provide a novel therapy for treating IVH patients as the nanoparticle-based siRNA approach provides heightened specificity for specific SFK gene(s) with less off target effects and this approach has been used in humans.

Acknowledgements:
This study was supported by AHA Beginning Grant-in-Aid 12BGIA12060381 (DZL) and NIH grant NS054652 (FRS). There were no conflicts of interest.
Abstract W P212: Combination Therapy With Amlodipine and Irbesartan Persists a Neuroprotective Effect Associated With Glial Deactivation on Paraventricular Nucleus in Hypertensive Rats
Authors: Hasegawa Yu , Nakagawa Takashi , Uekawa Ken , Ma Minglie , Lin Hakubun , Kusaka Hiroyuki , Katayama Tetsuji , Sueta Daisuke , Toyama Kensuke , Koibuchi Nobutaka , Kim-Mitsuyama Shokei 
Published: March 2022

Although combination therapy with calcium channel antagonist and angiotensin II receptor blocker is sometimes more effective for hypertension than monotherapy, it is little known the significant roles against stroke onset. In this study, we investigated the beneficial effect of the combination therapy with amlodipine and irbesartan against stroke onset in stroke-prone spontaneously hypertensive rats (SHRSP). High-salt-loaded SHRSP were assigned to 1)vehicle, 2)amlodipine (AM; 2mg/kg/day), 3)irbesartan (IR; 20mg/kg/day), and 4)AM+IR. The drugs were given every day until 35 days. Incidences of neurological deficit and mortality were monitored every day and blood pressure was measured at 7 and 28 days. Cerebral blood flow (CBF), weight of brain and left ventricle (LV) and histological evaluations were conducted at 42 days. The blood pressure in AM and AM+IR groups were significantly reduced compared with that in vehicle groups. Although the incidence of neurological deficit and mortality until 28 days were 90% and 40% in vehicle group, the rats in treatment groups were almost healthy until 35 days. After the drugs discontinued, abnormal signs were frequently seen in monotherapy groups until 42 days (neurological deficit; AM 50%, IR 50%, AM+IR 0%, mortality; AM 30%, IR 10%, AM+IR 0%). Although there was no significant difference in CBF among the groups, the weight of brain and LV in AM+IR group were decreased compared with those in single treatment groups.
Histological findings showed that glial activation at paraventricular nucleus and atrophy of white matter were more seen in stroke group compared with non-stroke groups. These data suggest that the therapy with AM+IR persist a neuroprotective effect against hypertension-induced stroke onset and the effect might associate with glial deactivation on paraventricular nucleus.
Abstract W P278: Defining the Role of the Nurse in Transitions of Care Within a Comprehensive Stroke Center (CSC)
Authors: Mathiesen Claranne , Conahan Erin M 
Published: March 2022

Transitions in care are a top priority for the US health care system as well as a core component of the CSC standards. Nurses are key in facilitating care from admission to discharge ensuring successful transitions through a stroke health challenge. Impetus to examine hospital readmission rates has been heightened by public reporting and potential CMS financial penalities.
The purpose of this presentation is to describe an interdisciplinary approach in planning care transitions supporting discharge. Our experience as a recently certified CSC identified opportunities for improvement in stroke care transitions.
A Stroke Continum Subgroup was formed including key stakeholders in partnering rehab facilities, inpatient rehab, home care, and stroke inpatient units to examine care transitions. Focused efforts evaluated discharge resources emphasizing patient and caregiver assessment, caregiver preparedness, and educational materials. Areas developed to support transitions included: standard caregiver resources including respite needs, daily discharge huddle identifying home needs and 7-day phone follow-up process. Metrics tracked included length of stay, discharge disposition, number of patients surveyed, number of caregivers provided educational materials and readmissions.
Developing interdisciplinary relationships promoted improvements in communication that lead to improved patient transitions related to follow up care, medication reconciliation and sharing of clinical information to promote continuity of care. At one year, 75% of patients received a structured post-discharge phone call which continues to identify opportunities to assist with scheduling follow up care, support early recognition of post stroke depression and ensure caregivers utilize respite resources. Our 30 day readmission rates in our ischemic stroke patients decreased to 7%, an overall 5% reduction from previous year.
Assessment of patient and caregiver needs after discharge can be difficult and requires a coordinated multidisciplinary effort with multi-prong interventions. Development of a Stroke Care Continum team allowed the CNS and Stroke Director to work with both inpatient and outpatient stakeholders.
Abstract W P281: Inter-Rater Reliability of Clinical Decision Making Based on Recorded Telemedicine Assessments and Case Histories
Authors: Lightbody Catherine E , Davies Paul , Emsley Hedley , Fitzgerald Jane , Ford Gary , Howell Laura , Leathley Michael J , McLoughlin Alison , May Carl , Price Christopher , Sutton Christopher , Watkins Caroline 
Published: March 2022

Background:
Patient outcomes are improved by reducing time, and increasing access, to stroke-specialist consultation and treatment. Telemedicine may ensure earlier and wider access to stroke-specialist consultation. However, reliable and accurate decision making is necessary by various professional groups in the emergency department in order for the telemedicine assessment to be initiated.

Aim:
To explore the inter-rater reliability of clinical decision making by various health professionals, when using telemedicine assessments in acute stroke.

Method:
Twenty-six telemedicine assessments in patients with suspected stroke (final/gold standard diagnosis: 16 strokes and 10 non-strokes) were recorded, edited and then presented with case histories. Health professionals viewed 6, randomly selected assessments and rated: whether ‘stroke or not’; level of confidence with their diagnosis. Data were analysed using Cohen’s kappa (K) with 95% confidence interval (CI) calculated using bias-corrected bootstrapping in STATA with 10000 replicates. Sensitivity and specificity were estimated.

Results:
Forty raters: 13 stroke physicians, 15 stroke nurses, 12 non-stroke specific staff (NSS) (including 3 ED consultants, 8 registrars and 1 neurologist). Median of 8 raters per assessment.

For ‘stroke or not’, agreement between all health professions was fair (K=0.36, CI 0.22-0.54); correctly diagnosing whether the patient was ‘stroke or not’ on 8 occasions, Sensitivity 77% (98/128), Specificity 67% (45/67).
Agreement within each health professional group ranged from K=0.37 (stroke physicians and nurses) to K=0.43 (NSS group), although CIs were wide. Sensitivity ranged from 74% (stroke physicians) to 81% (NSS group); specificity from 58% (stroke physicians) to 74% (NSS group).
Median confidence was highest in 4 of the 8 on which all raters agreed the ‘stroke or not’ diagnosis.

Conclusion:
Agreement was ‘fair’ overall and was similar for all groups, although CIs were wide. Nurses’ agreement or diagnostic accuracy were similar to stroke physicians and NSS doctors when rating telemedicine consultations.
Abstract W P349: Prediction of Major Adverse Cardiovascular Events by Age-Normalized Carotid Intimal Medial Thickness.
Authors: Rembold Christopher M , Nketiah Emmanuel , Rembold Karen E 
Published: March 2022

Background:
Increases in carotid intimal medial thickness (CIMT), as measured by noninvasive ultrasonography, have been associated with increased risk of myocardial infarction and stroke. From 706 patients who had CIMT measured between 1995 and 2003 at the University of Virginia, we created age-specific quartiles of carotid thickness. Over a mean follow-up of 4.8 years, we found that bulb and internal but not common CIMT predicted the combined endpoint of myocardial infarction, stroke, and revascularization (Atherosclerosis 187:186, 2006). We now present the analysis as of 2012 for CIMT to predict major adverse cardiovascular events in a population of patients referred for carotid IMT measurement.

Methods:
From 1995-2012, 1427 patients had carotid IMT measured at the University of Virginia’s Preventive Cardiology practice. In 2012, we successfully contacted 1259 of these patients to determine clinical outcomes. The 1259 patients were entered into a database and odds ratios were calculated with logistic regression in SAS.

Results:
Over a mean follow-up period of 7.8 years (range, 1 to 16), 30 patients died and 66 had major adverse cardiovascular events (MACE): 17 patients had CV death/myocardial infarction; 20 required revascularization; and 29 had a stroke or transient ischemic attack.

The highest quartile of bulb CIMT demonstrated an odds ratio for MACE of 7.2 (95% confidence interval, 3.0 to 18.6; P<0.001) when compared to the quartile with the lowest thickness (P<0.001 for trend).
The highest quartile of internal CIMT demonstrated an odds ratio for MACE of 3.1 (95% confidence interval, 1.2 to 8.3; P=0.02) when compared to the quartile with the lowest thickness (P=0.009 for trend).
Common carotid IMT did not significantly predict MACE (p=0.23).
The highest quartile of bulb CIMT demonstrated an odds ratio for mortality of 3.4 (95% confidence interval, 1.03 to 11.2; P=0.044) when compared to the quartile with the lowest thickness (not significant for common or internal CIMT).

Conclusions:
Age-normalized measurement of bulb and internal but not common CIMT appear to predict which individuals would most benefit from aggressive risk-factor modification.
Abstract 150: Complications and Outcomes of Thrombolysis in Stroke Patients Aged 90 and Over: UK National Registry Data
Authors: Paley Lizz , Bray Benjamin , James Martin , Tyrrell Pippa , Behrouz Reza , Smith Craig J , Di Napoli Mario , Cloud Geoffrey , Rudd Anthony ,   On behalf of the SSNAP Collaboration
Published: March 2022

Introduction:
National clinical guidelines in England and Wales recommend that intravenous thrombolysis is provided without restriction based on age. However, thrombolysis trials have included very few patients aged 90 and over. We therefore analysed data from the national stroke register of England and Wales to describe the safety and outcomes of thrombolysis in patients aged 90 and over.

Methods:
Data were extracted from the national stroke register (Sentinel Stroke National Audit Programme (SSNAP)) of adults with acute ischemic stroke treated in all hospitals in England and Wales from April 2013-March 2015.

Results:
Of 128826 adults with acute ischemic stroke admitted to 202 hospitals, 14854 (11.5%) were aged 90 or over. Of these, 1262 (8.5%) were treated with intravenous alteplase (iv-tPA).

Females comprised 70.0% of treated patients aged 90 or over, 6.3% had stroke onset whilst already an inpatient, 65.0% were independent prior to stroke (mRS of 2 or less), 71.2% were fully conscious upon arrival at hospital and 37.2% had a diagnosis of atrial fibrillation prior to stroke. The median age of the thrombolysed patients was 92 (IQR 91-94), similar to patients aged 90 or over who were not treated. Median NIHSS score was 14 (IQR 9-20).
Following tPA, 12.5% of patients had complications; 4.8% had symptomatic intracranial hemorrhage, 0.7% had angioedema, 0.6% had extracranial bleeds and 6.6% had some other type of tPA complication.
The median NIHSS 24h after tPA was 10 (IQR 4-18). Of the 871 patients (69.0%) who had a fully completed NIHSS at arrival and at 24h after thrombolysis, the median improvement was 3 points on the scale (IQR 0-7).
Inpatient case fatality rate was 32.8%, 20.9% were independent upon discharge from inpatient care (Rankin 2 or below), 14.1% were newly institutionalised into a care home (21.0% of those discharged alive).

Conclusions:
Patients aged 90 and over treated with iv-tPA have a similar rate of complications as reported for younger patients in national registries and clinical trials. However stroke in this age group carries a high risk of mortality and a high proportion of survivors are discharged to long term care for the first time.
Abstract 7: Thrace Study: Final Results
Authors: Bracard Serge , Guillemin Francis , Ducrocq Xavier ,   THRACE Investigators
Published: March 2022

Thrace is a French randomized, multicenter, controlled trial on mechanical thrombectomy for large cerebral arteries acute occlusions.
Primary objective was to determine whether a combined IVT/IAMT is superior to standard IV rTpa alone when initiated within 4h of acute ischemic stroke onset in adult patients with moderate-to-severe strokes (NIHSS>10) due to large artery occlusion. The primary outcome measure was the good clinical outcome (mRs 0-2) at 3 months.

Complete data were analyzed for the 2
nd
intermediate analysis using O’Brien and Fleming stopping rules.

Results:
412 patients were included. For the second intermediate analysis, 395 patients were considered. Data were complete and monitored for 385 patients (195 IV/ 190 IV+IAMT).

The mean age of our population was 62.5 years and the median NIHSS= 18. Occlusions were located on C1 in 57 (14,8%) and M1 in 326 cases (84,6%) At 3 months, the difference of good outcome between the two arms was significant according to the O’Brien-Fleming boundaries.

Conclusion:
After this intermediate analysis, THRACE was considered as positive and the Scientific Committee, following the DSMB advice, decided to stop the study. The final results will be presented.