Tetrahydrofolate attenuates cognitive impairment after hemorrhagic stroke by promoting hippocampal neurogenesis via PTEN signaling

 Ask your competent? doctor WHOM EXACTLY is going to do the research on ischemic stroke!

Tetrahydrofolate attenuates cognitive impairment after hemorrhagic stroke by promoting hippocampal neurogenesis via PTEN signaling

Xuyang Zhang, Qingzhu Zhang, Qian Zhang, Haomiao Wang, Yi Yin, Huanhuan Li, Qianying Huang, Chao Guo, Jun Zhong, Tengyuan Zhou, Yujie Chen, Zhi Chen, Qiao Shan and Rong Hu

eNeuro 10 May 2024, ENEURO.0021-24.2024; DOI: https://doi.org/10.1523/ENEURO.0021-24.2024

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Abstract

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.

Significance Statement Intracerebral hemorrhage (ICH) has been associated with cognitive dysfunction, yet its underlying mechanism remains elusive. Tetrahydrofolate (THF) has shown potential in promoting the proliferation of neural stem cells (NSCs), but its specific impact on cognitive recovery following ICH is still to be confirmed. Through the utilization of the Nestin-GFP genetic marker to track endogenous NSCs in mice, our study revealed that THF could regulate PTEN pathway to ameliorate cognitive impairment post-ICH by enhancing the proliferation of NSCs and sustaining neurogenesis. These findings contribute to valuable insights into the molecular mechanisms involved and suggest potential clinical applications for enhancing cognitive function recovery after ICH.

Effectiveness of Robot-Assisted Lower Limb Rehabilitation on Balance in People with Stroke: A Systematic Review, Meta-analysis, and Meta-regression

 If this is effective, where is the protocol publicly located so survivors can find it and bring it to their doctor/therapist attention? Top down does not work, hospitals do not have a research analyst whose only job is to follow stroke research and get it implemented in the hospital.

Effectiveness of Robot-Assisted Lower Limb Rehabilitation on Balance in People with Stroke: A Systematic Review, Meta-analysis, and Meta-regression

Part of the book series: Communications in Computer and Information Science ((CCIS,volume 2084))

Included in the following conference series:

• Nordic Conference on Digital Health and Wireless Solutions​

• Riku Yli-Ikkelä,
• Aki Rintala,
• Anna Köyhäjoki,
• Harto Hakonen,
• Hilkka Korpi,
• Mirjami Kantola,
• Sari Honkanen,
• Outi Ilves,
• Tuulikki Sjögren,
• Juha Karvanen &
• Eeva Aartolahti
  

Abstract

The objective of this study was to evaluate the effectiveness of robot-assisted lower-limb rehabilitation on balance in stroke patients and to explore the covariates associated with these effects.

A systematic literature search was carried out in four databases (MEDLINE (Ovid), CINAHL, PsycINFO, and ERIC) for studies published from inception to 25^th of March 2022. Studies on robot-assisted lower-limb rehabilitation with a randomized controlled trial (RCT) design, participants with stroke, a comparison group with conventional training, and balance-related outcomes were included. Studies were assessed for Cochrane Risk of Bias 2 and quality of evidence. Meta-analysis and meta-regression were performed.

A total of 48 (RCT) with 1472 participants were included. The overall risk of bias in the included studies was unclear (n = 32), high (n = 15) or low (n = 1). Compared to conventional rehabilitation, robot-assisted lower-limb rehabilitation interventions were more effective for balance improvement (Hedges’ g = 0.25, 95% CI: 0.10 0.41). In meta-regression, a relationship between the training effect was observed with the time since stroke, explaining 56% of the variance (p = 0.001), and with the ankle robots, explaining 16% of the variance (p = 0.048). No serious adverse events related to robot-assisted training were reported.

Robot-assisted lower-limb rehabilitation may improve balance more than conventional training in people with stroke, especially in the acute stage. Robot-assisted lower-limb rehabilitation seems to be a safe rehabilitation method for patients with stroke. To strengthen the evidence, more high-quality RCTs with adequate sample sizes are needed.

You have full access to this open access chapter,  Download conference paper PDF

Fostering a Culture of Research: From Recommendations to Implementation

 Now if survivors could just get access to the library/electronic databases, we could probably solve stroke on our own. A major failing of this is I see nothing on a strategy that researchers follow. No strategy; researchers are just shooting in the dark.

Fostering a Culture of Research: From Recommendations to Implementation

Ivy Anne Sebastian,

Ana Claudia de Souza,

Meron Awraris Gebrewold,

Dorcas B.C. Gandhi,

Vanessa Cano-Nigenda,

Caleb Ferguson,

Mehari Gebreyohanns and

Vasileios-Arsenios Lioutas

Originally published1 May 2024https://doi.org/10.1161/STROKEAHA.123.042385Stroke. 2024;0

 

 

 

 

 

Footnotes

For Sources of Funding and Disclosures, see page XXX.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.123.042385.

Correspondence to: Meron Awraris Gebrewold, MD, College of Health Sciences, Addis Ababa University, Kasangula Rd, Lusaka, Zambia, Ethiopia. Email merianair@yahoo.com

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

 Didn't your competent? doctor figure out a protocol on this 5 years ago? NO? So you DON'T have a functioning stroke doctor? Why are you seeing them?

• endothelial nitric oxide (1 post to January 2019)

I guess a major problem with this it has to be performed before your stroke. You'll need time travel or precognitive dreams about your upcoming stroke.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

eNOS

Shinya Yokomizo,

Timo Kopp,

Malte Roessing,

Atsuyo Morita,

Seeun Lee,

Suin Cho,

Emiyu Ogawa,

Eri Komai,

Kazumasa Inoue,

Masahiro Fukushi,

Susanne Feil,

Hyung-Hwan Kim,

Denis E. Bragin,

… See all authors

Originally published4 Apr 2024https://doi.org/10.1161/STROKEAHA.123.045358Stroke. 2024;0

Abstract

BACKGROUND:

The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

METHODS:

This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits.

RESULTS:

Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm² improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes.

CONCLUSIONS:

Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

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Stroke Recovery–Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition

 

In my case there is no interhemispheric inhibition since it is dead brain over there. So what is your dead brain rehab protocol? There must be millions of us out there and I've never seen any research on that problem.

Stroke Recovery–Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition

Sylvain Harquel,

Andéol Cadic-Melchior,

Takuya Morishita,

Lisa Fleury,

Adrien Witon,

Martino Ceroni,

Julia Brügger,

Nathalie H. Meyer,

Giorgia G. Evangelista,

Philip Egger,

Elena Beanato,

… See all authors

Originally published19 Apr 2024https://doi.org/10.1161/STROKEAHA.123.045174Stroke. 2024;0

Abstract

BACKGROUND:

Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke.

METHODS:

Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation.

RESULTS:

From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (P_cluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics.

CONCLUSIONS:

The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

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Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus

You might want to make sure your hospital has this written into protocols and training done so when you show up with this your doctors aren't 'winging it'.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus

• Hassan Aboul-Nour, MD
• Qasem Alshaer, MD
• Fatima Chughtai Khalid, MD
• 
  
• Mahmoud H. Mohammaden, MD, MSc, PhD
• Diogo C. Haussen, MD
• Jaydevsinh N. Dolia, MD
• Show all authors

Published:May 06, 2024DOI:https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.107760

ABSTRACT

BACKGROUND

Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology.

METHODS

Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded.

RESULTS

During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results.

CONCLUSION

Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

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Dementia Mortality Tied to Olive Oil Consumption

 The real question needing answering: 'Does what amount of olive oil consumption prevent dementia?' Now that would be useful to know, this death thing, not so much!

Dementia Mortality Tied to Olive Oil Consumption

Results appear to be independent of overall diet quality

by Judy George , Deputy Managing Editor, MedPage Today May 6, 2024

Key Takeaways

• Higher olive oil intake was associated with a lower risk of dementia-related death in a large longitudinal study.
• The relationship remained significant after adjusting for overall diet quality.
• The association was significant for women, but not men.

Higher olive oil intake was associated with a lower risk of dementia-related mortality, a prospective study of 90,000 healthcare professionals showed.

Eating at least 7 g of olive oil daily -- about a half tablespoon -- was tied to an adjusted 28% lower risk of dementia-related death (pooled hazard ratio [HR] 0.72, 95% CI 0.64-0.81) compared with never or rarely consuming olive oil (P for trend <0.001) over 28 years of follow-up, reported Anne-Julie Tessier, RD, PhD, of the Harvard T.H. Chan School of Public Health in Boston, and co-authors.

The relationship remained significant after adjusting for diet quality, including adherence to a Mediterranean diet, and after accounting for APOE4 gene status, the researchers reported in JAMA Network Openopens in a new tab or window.

Replacing 5 g (about 1 teaspoon) of margarine and mayonnaise with the equivalent amount of olive oil daily was associated with an 8-14% lower risk of dementia mortality, they noted. Substitutions for other vegetable oils or butter were not significant.

Onset of most dementia types is gradual and progression is slow, making dementia-related mortality difficult to study, Tessier noted. "To our knowledge, this is the first study to examine diet, specifically olive oil, in relation to dementia death," she told MedPage Today.

"Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association to be regardless of this factor," Tessier pointed out.

"Current dietary guidelines regarding fats are mainly based on evidence related to cardiovascular health," she added. "Our study contributes to supporting current dietary guidelines recommending choosing vegetable oils such as olive oil, but extends these recommendations to brain-related health."

A number of observational studies have found relationships between brain health and plant-based diets like the Mediterranean or MIND dietopens in a new tab or window that include olive oil, though some research has suggested diet and dementiaopens in a new tab or window may not be related.

"As part of the Mediterranean diet, olive oil may exert anti-inflammatory and neuroprotective effects due to its high content of monounsaturated fatty acids and other compounds with antioxidant properties such as vitamin E and polyphenols," Tessier and colleagues noted.

The researchers followed 60,582 women from the Nurses' Health Study and 31,801 men from the Health Professionals Follow-up Study from 1990 to 2018. Previous research from these cohorts showed that higher olive oil consumption was tied to lower cardiovascular diseaseopens in a new tab or window risk and lower neurodegenerative diseaseopens in a new tab or window mortality.

Mean baseline age was about 54, and participants were free of cardiovascular disease and cancer at baseline. Dementia death was ascertained from death records.

Every 4 years, participants reported olive oil intake on food frequency questionnaires. Scores on the Alternative Healthy Eating Indexopens in a new tab or window and alternative Mediterranean dietopens in a new tab or window scale were used to assess overall diet quality.

Mean olive oil intake was 1.3 g/day at baseline and went up over time. During 28 years of follow-up, 4,751 dementia-related deaths occurred.

The association between dementia-related death and olive oil intake was significant for women (adjusted HR 0.67 (95% CI 0.59-0.77), but not men (HR 0.87, 95% CI 0.69-1.09). Joint analyses showed that participants with high olive oil intake had a low risk for dementia-related mortality, regardless of diet quality scores.

In a subset of about 27,000 participants who were genotyped, the overall results were similar after adjusting for the presence of an APOE4 allele (adjusted HR comparing high vs low olive oil intake of 0.66, 95% CI 0.54-0.81, P for trend <0.001).

Olive oil consumption may lower dementia mortality by improving vascular health, Tessier and colleagues suggested, though incident cardiovascular disease, hypercholesterolemia, hypertension, and diabetes were not significant mediators of the relationship between olive oil and dementia-related death in this study.

The study had several limitations, including the possibility of reverse causation, the researchers acknowledged. While results remained consistent after accounting for socioeconomic status and important covariates, residual confounding may have occurred. The study population was predominantly white and results may not apply to others.

In addition, some margarine and mayonnaise contained considerable levels of partially hydrogenated oils during the course of the study, which the FDA warned aboutopens in a new tab or window in 2013 and subsequently bannedopens in a new tab or window.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This study was supported by the National Institutes of Health.

Tessier was supported by the Canadian Institutes of Health Research. Co-authors reported relationships with the Novo Nordisk Foundation, WebMD, Prada Foundation, Biogen, Moderna, Merck, Roche, and Glaxo Smith Kline.

Primary Source

JAMA Network Open

Source Reference: opens in a new tab or windowTessier A, et al "Consumption of olive oil and diet quality and risk of dementia-related death" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.10021.

Daily Life Upper Limb Activity for Patients with Match and Mismatch between Observed Function and Perceived Activity in the Chronic Phase Post Stroke

 You described a problem, DID NOTHING TO SOLVE IT! Useless!

Daily Life Upper Limb Activity for Patients with Match and Mismatch between Observed Function and Perceived Activity in the Chronic Phase Post Stroke

Bea Essers 1, * , Marjan Coremans 1 , Janne Veerbeek 2 , Andreas Luft 3,4 and Geert Verheyden 1   Citation: Essers, B.; Coremans, M.; Veerbeek, J.; Luft, A.; Verheyden, G. Daily Life Upper Limb Activity for Patients with Match and Mismatch between Observed Function and Perceived Activity in the Chronic Phase Post Stroke. Sensors 2021, 21, 5917. https://doi.org/10.3390/ s21175917 Academic Editor: James F. Rusling Received: 26 July 2021 Accepted: 28 August 2021 Published: 2 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Rehabilitation Sciences, KU Leuven, 3001 Leuven, Belgium; marjan.coremans@kuleuven.be (M.C.); geert.verheyden@kuleuven.be (G.V.) 2 Luzerner Kantonsspital, Neurocenter, 6000 Lucerne, Switzerland; janne.veerbeek@luks.ch 3 Division of Vascular Neurology and Neurorehabilitation, Department of Neurology and Clinical Neuroscience Center, University of Zurich and University Hospital Zurich, 8091 Zurich, Switzerland; andreas.luft@usz.ch 4 Cereneo, Center for Neurology and Rehabilitation, 6354 Vitznau, Switzerland * Correspondence: bea.essers@kuleuven.be  

Abstract: 

 

 We investigated actual daily life upper limb (UL) activity in relation to observed UL motor function and perceived UL activity in chronic stroke in order to better understand and improve UL activity in daily life. In 60 patients, we collected (1) observed UL motor function (Fugl-Meyer Assessment (FMA-UE)), (2) perceived UL activity (hand subscale of the Stroke Impact Scale (SIS- Hand)), and (3) daily life UL activity (bilateral wrist-worn accelerometers for 72 h) data. Data were compared between two groups of interest, namely (1) good observed (FMA-UE >50) function and good perceived (SIS-Hand >75) activity (good match, n = 16) and (2) good observed function but low perceived (SIS-Hand ≤75) activity (mismatch, n = 15) with Mann–Whitney U analysis. The mismatch group only differed from the good match group in perceived UL activity (median (Q1–Q3) = 50 (30–70) versus 93 (85–100); p < 0.001). Despite similar observed UL motor function and other clinical characteristics, the affected UL in the mismatch group was less active in daily life compared to the good match group (p = 0.013), and the contribution of the affected UL compared to the unaffected UL for each second of activity (magnitude ratio) was lower (p = 0.022). We conclude that people with chronic stroke with low perceived UL activity indeed tend to use their affected UL less in daily life despite good observed UL motor function. Keywords: stroke; upper limb sensor activity; patient-reported outcome measures

Expert Interview: Update on AHA’s Get With The Guidelines Series

 Notice the word 'GUIDELINES' NOT RESULTS!

 Anytime I see 'care' or guidelines in any press release I know the stroke hospital is not willing to disclose actual results because they are so fucking bad, it wouldn't look good, so misdirection is used. Don't fall for that misdirection!

Big fucking whoopee.

 

 But you tell us NOTHING ABOUT RESULTS. They remind us they 'care' about us multiple times and follow guidelines but never tell us how many 100% recovered.  You have to ask yourself why they are hiding their incompetency by not disclosing recovery results.  ARE THEY THAT FUCKING BAD?

Three measurements will tell me if the stroke hospital is possibly not completely incompetent; DO YOU MEASURE ANYTHING?  I would start cleaning the hospital by firing the board of directors, you can't let incompetency continue for years at a time.

There is no quality here if you don't measure the right things.

1. tPA full recovery? Better than 12%?
2. 30 day deaths? Better than competitors?

3. rehab full recovery? Better than 10%?

 

You'll want to know results so call that hospital president(whomever that is) RESULTS are; tPA efficacy, 30 day deaths, 100% recovery. Because there is no point in going to that hospital if they are not willing to publish results.

Expert Interview: Update on AHA’s Get With The Guidelines Series

Tori Rodriguez, MA, LPC, AHC

|

May 10, 2024

Credit: Getty Image

The AHA and ASA Get With the Guidelines series aims to increase the consistent implementation of guidelines-based CVD and stroke care in hospitals.

Nearly 25 years ago, the American Heart Association (AHA) and the American Stroke Association developed the Get With The Guidelines (GWTG) series^1,2 to increase the consistent implementation of guidelines-based care in hospitals for patients with cardiovascular disease (CVD) and stroke.^1-3

The GWTG suite of programs aims to improve patient care and outcomes through resources such as provider education, quality improvement measures, and patient registries, with an overarching goal of reducing death and disability associated with CVD and stroke.^4,5  

For updates on the current status and achievements of the GWTG series, Cardiology Advisor interviewed AHA volunteer Gregg Fonarow, MD, FAHA, interim chief of the division of cardiology and the Eliot Corday Chair in Cardiovascular Medicine and Science at the University of California, Los Angeles (UCLA). Dr Fonarow is also director of the Ahmanson-UCLA Cardiomyopathy Center and co-director of the UCLA Preventative Cardiology Program.

How did the GWTG series come about? Why was there a need to create such a program in the various areas of focus, such as stroke and atrial fibrillation?

Dr Fonarow: In 1999, AHA volunteers identified a need to establish a mechanism by which hospitals could stay up to date with the latest clinical guidelines and recommendations to improve cardiovascular care quality and clinical outcomes. The AHA had set an ambitious goal to reduce death and disability due to CVD by 25% by 2010.¹ With that goal in mind, AHA created the very first GWTG module for coronary artery disease, beginning with a regional pilot program. Based on this initial success, GWTG expanded nationally in 2001 and then launched additional modules.⁶

All GWTG [Get With the Guidelines] modules are associated with significant improvements in multiple processes of care strongly linked to improved outcomes.

This performance-improvement, registry-based approach would allow sites to evaluate their patient population against the most recent guideline-directed medical therapies, engage in collaborative learning, and share best practices. In addition to the technical support for the effort, AHA introduced the role of Quality Improvement consultants. Every GWTG hospital is provided a skilled quality consultant to assist as they use the registry to report on performance, identify opportunities for process improvement, and support their facility accreditation and certification with data from the registry. Sites also have the opportunity to be recognized by the AHA for their consistent performance. 

GWTG is now available for atrial fibrillation, coronary artery disease including chest pain, heart failure, stroke, and resuscitation to support cardiac arrest care.² 

Since the program’s inception, what have been some of the most significant achievements in terms of improved processes and outcomes at participating hospitals?

Dr Fonarow: All GWTG modules are associated with significant improvements in multiple processes of care strongly linked to improved outcomes. The AHA’s 2010 Strategic Goal was able to be met 3 years early, in 2007, in part based on GWTG.⁶

Currently, more than 2,600 US hospitals participate in one or more GWTG program module. That means nearly 80% of the American population has access to the program. Plus, since the creation of the program, more than 13 million US patient records have been entered into the registry.² 

A few of the most significant achievements include:

• Demonstrating that participation in GWTG could reduce and even eliminate race/ethnicity- and sex-based disparities in the use of guideline recommended therapies. Equitable care provision during hospitalization has been achieved for most of the achievement measures targeted in GWTG modules.^7,3
• Learning that recognition, along with targeted quality improvement efforts, can drive adherence with the most recent clinical trial evidence and guidelines. An example was the development of the Target: Stroke program. The primary goal of this initiative was to reduce the door-to-needle times, as time to treatment is strongly associated with stroke outcomes. In just the first year of Target: Stroke, participating hospitals reduced the time from 80 minutes pre-intervention to 68 minutes, and patients experienced substantially improved clinical outcomes.⁸ In subsequent phases of the project, we have seen continued improvement and have now added Target: Stroke Advanced Therapy to evaluate and monitor interventional treatment. 
• Integrating Target: Type 2 Diabetes in the Get With The Guidelines – Stroke, CAD, and HF modules, so we are caring across diagnoses.
• Targeted implementation of the April 2022 Heart Failure guidelines in a pilot program that utilized Get With The Guidelines – Heart Failure. The emphasis was on the provision of quadruple therapy, which has increased the provision of guideline-directed medical therapies with participating sites from 14% to 49%. More importantly, the impacted patients had improvement in their LVEF [left ventricular ejection fraction]– moving from 9% at baseline to 55%.⁹         
• Emphasizing systems of care for ST elevation myocardial infarction (STEMI). The GWTG-Coronary Artery Disease module meets the needs to measure and improve care from first medical contact – ie EMS or referring hospital – to reperfusion at the receiving center. Cohorts (eg, regions, states, and health systems) can use a Get With The Guidelines – Super User account to create data reports that drive performance as a group.   

What are the key factors driving the success of the GWTG programs?

Dr Fonarow: Understanding quality measurement is critical to improving patient care and making the certification process simple. Participating hospitals take their efforts a step further to ensure teams are using current guideline-directed treatments, setting best in class goals, and using peer benchmarks to compare performance. The integration of the most current guidelines is a key benefit to sites.  

Each participating hospital and health system works with a program consultant to implement, interpret data, identify areas for improvement, and articulate recommendations internally. It’s like having a consultant for the organization’s quality improvement objectives – and a significant reason these programs are so successful.

Also, the GWTG registry tool collects data from participating hospitals, allowing health care leaders and researchers to examine trends and continue bringing current evidence-based guidance to care delivery at hospitals across the country.

What are examples of situations in which deviation from the guidelines may be necessary – for example, due to access issues, limited resources, or patient-specific scenarios?        

Dr Fonarow: As with any therapy, there are contraindications to some treatments, and collecting information on contraindications is actually built into the registry. Sites are provided the opportunity to document the reason why a patient was excluded from the treatment and can use that information to evaluate overall treatment and considerations for process improvement. And of course, the final decision on treatment resides with the patient and their caregivers. They can decide against a treatment, and GWTG allows for that documentation. 

What areas are targeted for further development, and what are some of the program goals for the future?

Dr Fonarow: Until recently, the biggest gap in reaching all hospitals pertained to the small or rural hospital. These sites were less likely to join the quality improvement program due to resource limitations and low volumes of patients. However, the data shows these residents are at 30% higher risk of stroke, 40% more likely to develop heart disease, and live an average of 3 years fewer than urban counterparts.¹⁰ Yet, when rural hospitals did participate in GWTG, care quality improved, and in many cases performance rivaled that of urban hospitals. The AHA has now launched the Rural Community Network, which is open to all rural hospitals to join GWTG. This program aims to help close those gaps. More than 350 new hospitals have signed up so far.

As newer therapies are discovered, tested, proven to provide patient-centered outcomes, and are integrated into the national guidelines, these therapies can be rapidly integrated into GWTG. The program aims to further enhance these processes, so that each patient receives the best evidence-based care at the right time, at the right dose, equitably, reliably, every time. This is aligned with the AHA’s goal of advancing cardiovascular health for all, including identifying and removing barriers to health care access and quality.

PREVENT, TREAT AND SUPPORT: A MANIFESTO FOR STROKE SURVIVORS ;ESO(European Stroke Organization)

You're missing the most important part! A STRATEGY! With no strategy, researchers won't solve the correct problem, they'll be shooting in the dark! Doesn't anyone in stroke have two functioning neurons they can rub together for a spark of intelligence? Once again proving we have fucking failure of stroke associations!

PREVENT, TREAT AND SUPPORT: A MANIFESTO FOR STROKE SURVIVORS

With NO strategy, any research done is useless!

Intravenous Alteplase in Patients With Minor Acute Ischemic Stroke — Where is the Limit?

 Survivors don't want 'better'. They want 100% recovery! WHEN THE HELL ARE YOU GOING TO DO THE WORK TO GET THERE? Maybe after you are the 1 in 4 per WHO that has a stroke?  Perhaps you might want to start researching those solutions now, while you still can.

Intravenous Alteplase in Patients With Minor Acute Ischemic Stroke — Where is the Limit?

• Christian Boehme, MD, PhD @chris7ianb

Originally published May 3, 2024 10.1161/blog.20240426.989508

Zhang Y, Lv T, Nguyen TN, Wu S, Li Z, Bai X, Chen D, Zhao C, Lin W, Chen S, Sui Y. Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis. Stroke. 2024;55:883–892.

Intravenous thrombolysis (IVT) is probably the most effective weapon for stroke physicians in acute ischemic stroke to achieve a better functional outcome. Guidelines and treatment recommendations evolved from a strict NIHSS >3 points regime to a more liberal indication, namely the use in case of disabling symptoms, regardless of NIHSS-scoring. Guidelines do not recommend alteplase thrombolysis for patients with mild non-disabling symptoms (NIHSS 0–5).

At least half of acute ischemic stroke patients present with minor or mild symptoms at admission, but research showed that 29% of patients with minor stroke had a non-excellent outcome (mRS 2-6) after three months.¹ Reasons for this are most likely progressive strokes or recurrent strokes. Most major trials excluded patients with mild or minor symptoms; therefore, safety and efficacy of IVT in these patients is not entirely clear. Moreover, the exploration of effects on specific subgroups in previous meta-analyses is not sufficient to draw final conclusions.

 

 

 

 

 

 

 

Zhang et al. conducted a systematic review and meta-analysis on comparison of IVT with best medical therapy (BMT) in patients with minor stroke to find an answer to the question of IVT or no IVT in these patients.²

The inclusion criteria for this study were patients with minor ischemic stroke (NIHSS score, 0–5) who could receive thrombolysis within 4.5 hours after onset of stroke; IVT with alteplase; comparison: BMT (including dual antiplatelet therapy [DAPT] or single use); and reporting of functional outcomes and any safety outcomes in randomized controlled trials (RCTs) and observational studies. Studies with patients who received mechanical thrombectomy or bridging therapy were excluded. The primary outcome was excellent functional outcome at 90 days (mRS 0-1). Secondary outcomes included favorable functional outcome at 90 days (mRS 0-2), mortality, early neurological deterioration, recurrent stroke, and recurrent ischemic stroke. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and hemorrhagic transformation. Of 5393 publications found until August 2023, 3 RCTs and 17 observational studies were included.

Rates of excellent functional outcome (mRS 0-1) showed no significant difference comparing IVT and BMT (2252/2717, 82.89% versus 3295/4073, 80.90%, p=0.274). The pooled estimated effect on mRS score of 0-1 at 90 days was consistent in each predefined subgroup including age >80 years, disabling symptoms, comparing different antiplatelet regimes, large vessel occlusion, thrombolytic time window of 0 to 3 hours or 0 to 4.5 hours, baseline NIHSS score of 0-3 or 0-5 and premorbid mRS scores of 0 and 0-2. No differences were disclosed between subgroups.

Also, rates of favorable functional outcome (mRS 0-2) showed no significant difference (1790/1960, 91.33% versus 2878/3188, 90.28%, p=0.141). Mortality and recurrent stroke or recurrent ischemic stroke at 90 days also showed no difference comparing IVT and BMT. The study revealed a higher rate of early neurological deterioration, sICH, and hemorrhagic transformation in patients treated with IVT.

This meta-analysis showed no difference between IVT and BMT in patients with minor ischemic stroke (NIHSS score ≤5) regarding excellent or good functional outcome at 90 days. IVT was associated with an increased risk of safety outcomes, such as early neurological deterioration, sICH, and hemorrhagic transformation, while BMT was similar to IVT in preventing recurrent stroke and recurrent ischemic stroke. All in all, functional outcome of patients with nondisabling strokes is not improved by intravenous alteplase, and a small number of patients may actually be harmed by thrombolysis.

These results are subject to use of alteplase as thrombolytic therapy agent. No RCTs on other intravenous thrombolytics such as tenecteplase are available in patients with minor stroke. The TEMPO-2 trial could give more insight, but it is subject to patients with mild deficits and large vessel occlusion. The TRUST trial will assess urokinase in comparison to antiplatelet agents for the management of minor ischemic stroke and is ongoing. Limitations include the lack of a universal recognized definition of disabling symptoms and inconsistencies among the included studies in terms of the time of treatment initiation, baseline NIHSS score, definitions of minor stroke, and dosing paradigms of antiplatelets.

Stroke physicians often see spontaneous neurological improvement in patients with mild symptoms; therefore, these results seem reassuring. The critical question is, what makes a mild/minor stroke a non-disabling stroke? Stroke physicians want to rapidly administer IVT, but in cases like these, we should carefully weigh the risks and benefits and consider the patients’ life circumstances to evaluate if the suspected stroke is causing mild, truly non-disabling symptoms.³ For example, a vocalist with mild dysarthria might consider this a disabling symptom, and a waiter might consider mild paralysis of the non-dominant hand as disabling. It is, therefore, of uttermost importance to consider the whole picture and to carefully assess the risk for sICH like considering age and comorbidities in a setting where time is the enemy.

There are several questions which remain to be answered. First, the arrival of new thrombolytic agents for acute stroke reperfusion therapy, i.e., tenecteplase, might exploit other new RCTs to address the question if IVT with other substances — which are endowed with an increased half-life compared to alteplase — might reduce the risk of progressive stroke and show a beneficial effect on functional outcomes in acute minor ischemic stroke.

Second, most patients who receive IVT in case of mild symptoms in observational studies might be seen as being at a formally higher risk of neurological worsening and, therefore, received IVT despite minor symptoms. These scenarios could include cervical artery dissection, instable plaques, or intracranial stenosis — therefore, one has to raise the question of a selection bias in favor of IVT in these patients.

Third, one has to keep in mind the patients who undergo endovascular treatment and achieve a good outcome. The effect of endovascular treatment on functional outcomes in high-risk patients with minor stroke might narrow the treatment effect of IVT on functional outcomes.

Finally, future research might explore other beneficial effects of IVT and reperfusion in general besides short-term functional outcome, like cognitive function and poststroke dementia.

To conclude, IVT with alteplase seems not to be beneficial in non-disabling stroke to ameliorate functional outcome in the short-term. The arrival of tenecteplase in clinical practice, specific subgroups with potential benefit, and the exploration of other outcomes besides functional outcome after 3 months warrant further investigation of IVT in minor acute ischemic stroke.