Wash. judge dismisses stroke patient’s DUI protocol lawsuit

 You're going to have to be cognizant and capable enough to inform others that you're having a stroke. Obviously whatever training was provided here was totally inadequate!

Wash. judge dismisses stroke patient’s DUI protocol lawsuit

A judge dismissed a lawsuit against Puyallup police and Central Pierce Fire & Rescue filed by a woman who was misdiagnosed with DUI but was later found to have suffered a massive stroke

One for the Road: Stroke care missing the mark?

By Shea Johnson
The News Tribune

PUYALLUP, Wash. — A Pierce County Superior Court judge has dismissed a lawsuit that accused local authorities of negligence after a Puyallup woman was arrested for DUI but actually had suffered a stroke.

Jane Carhuff and a family representative sued the city of Puyallup and Central Pierce Fire & Rescue more than three years after her November 2019 arrest for which charges were dismissed, alleging that Puyallup police ignored protocol for DUI testing and firefighters rendered a medical opinion without the necessary expertise.

As a result, the 54-year-old postal worker spent more than three hours in custody reportedly acting strangely. A day or so after Carhuff returned home and her condition — alleged to have been the product of drug intoxication — didn’t improve, her family took her to a local hospital where she was diagnosed with having suffered a massive stroke, according to the suit.

The delay in receiving medical care significantly worsened Carhuff’s chances of recovery, and she continued to suffer strokes until her death in September 2023, according to the suit and her obituary.

In separate motions filed in court, the city of Puyallup and Central Pierce Fire & Rescue denied wrongdoing and sought to dismiss the case. Earlier this month, Judge TaTeasha Davis granted their motions, ending the case before a scheduled April trial, court records show.

“We were all stunned,” attorney Darrell Cochran, one of the lawyers representing Carhuff and her family representative, said in an interview Tuesday.

Cochran said the plaintiffs’ legal counsel planned to appeal Davis’ decision and, if successful, the case’s trial date would be reset.

The case hinged on whether Carhuff exhibited obvious signs of a stroke after she caused at least two crashes on her way to a doctor’s appointment. Attorneys for the city argued the plaintiffs’ own experts admitted she was not clearly showing such signs and that her behaviors were consistent with intoxication.

In a statement Wednesday, Puyallup City Attorney Joseph Beck expressed “deepest condolences” to Carhuff’s family on behalf of the city, calling her death “a profound tragedy.”

“We are grateful that the court, after a thorough review of all the facts presented, has determined that the City met the highest standard of care expected of law enforcement,” Beck said.

Central Pierce Fire & Rescue, which examined Carhuff prior to her arrest, argued in a court filing that emergency medical technicians acted appropriately.

“Central Pierce Fire & Rescue is committed to providing the highest standard of emergency medical care to our community,” a department spokesperson said in a statement Wednesday. “Our focus remains on serving with professionalism and compassion.”

Morning drive turns frantic

On Nov. 11, 2019, feeling ill, Carhuff embarked on a roughly 20-minute drive to a doctor’s appointment after eating breakfast with her brother’s wife and daughter, both of whom described her as acting normally, according to the lawsuit.

En route to her doctor, Carhuff suffered a medical emergency, inadvertently causing three crashes that badly damaged her vehicle before she arrived at her doctor’s office, a clinic at 610 S. Meridian, where she entered through the reception area and waited to be seen, the suit said.

All the while, Puyallup police frantically sought a hit-and-run driver, spurred by 911 calls from crash victims, including one who provided license plate information, according to the suit. Officers identified Carhuff as the suspect and learned her whereabouts from family upon visiting her home, leading police to respond to her doctor’s office, the suit said.

Central Pierce Fire & Rescue (CPFR) personnel also arrived at the scene.

The lawsuit alleged that Carhuff was mistreated by police and firefighters, despite purportedly being confused, disoriented and manifesting the effects of someone having a stroke.

Fire personnel conducted their own medical assessment, instead of consulting with Carhuff’s doctor or taking her to a local hospital roughly 300 yards away, according to the suit. Only Carhuff’s blood sugar was tested after she reportedly referenced being diabetic, the suit said, adding that CPFR concluded that she wasn’t in medical distress but under the influence of an unknown intoxicant.

In arresting Carhuff, police officers were accused of failing to follow standard DUI protocol by not conducting field-sobriety tests or contacting a drug-recognition expert, according to the suit.

In a response filed in court, the city of Puyallup did not dispute that Carhuff had been unsteady on her feet and unable to follow simple instructions; that three EMTs who examined her had reported finding no medical problem; or that she was later diagnosed with a stroke.

However, the city said it was reasonable for officers to conclude that Carhuff was intoxicated. In particular, Carhuff told officers she had taken the prescription sedative Ambien and severe-cold medication that morning, the city’s defense counsel said, noting that an expert witness for the plaintiffs acknowledged that Carhuff’s symptoms aligned with the effects of the sedative.

“It is undisputed she had something dry and crusty on her lips, had bloodshot and watery eyes, and her face was flushed,” the city’s legal counsel wrote in a court filing. “It is undisputed she acted confused.”

The plaintiffs’ legal counsel denied that Carhuff had taken prescription or other medication that would have impaired her ability to drive.

Other details were in dispute or later changed.

For instance, the two sides disagreed on the number of crashes Carhuff had been involved in on the way to her doctor’s appointment: The city said two, but Cochran told The News Tribune that it was indeed three.

The city also noted that Carhuff had been in custody in the Puyallup Jail for fewer than three hours before she bailed herself out. The original and amended lawsuits said bail was posted roughly eight hours after her arrest, but plaintiffs later reduced that time frame to three-plus hours in a subsequent filing, which Cochran said resulted from further investigation.

“We consider it a very strong case and one that’s very solidly on legal grounds,” he said Tuesday, insisting that there had been “absolutely no basis” for Carhuff’s arrest.

Law enforcement has an obligation to not worsen the health condition of people with whom it interacts, he said, “which is exactly what happened in this situation.”

Beck said the city of Puyallup would remain dedicated to fostering a safe and supportive environment for all of its residents.

“We understand the impact this case has had on the Carhuff family, and we continue to extend our heartfelt sympathies,” he said.

Diabetes status, duration, and risk of dementia among ischemic stroke patients

 You, your mentors and senior researchers don't read research, do you?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

5. Brain Bleeds Double Dementia Risk February 2025

The latest here:

Diabetes status, duration, and risk of dementia among ischemic stroke patients

• Jonguk Kim,
• Kyung-Do Han,
• Jeong-Yoon Lee,
• Ye Seul Yang,
• Dae Young Cheon,
• Jae-Jun Lee &
• Minwoo Lee 

Alzheimer's Research & Therapy volume 17, Article number: 58 (2025) Cite this article

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Abstract

Background

The influence of duration of type 2 diabetes mellitus (T2DM) on the likelihood of developing new-onset dementia in post-stroke population is not well understood.(It is if you read research!) Therefore, we aimed to clarify the relationship between the duration of T2DM and the risk of developing dementia in the post-stroke population.

Methods

Leveraging the Korean National Health Insurance Database, this study included 118,790 individuals with a history of stroke but no previous dementia diagnosis. We classified diabetes status into five categories: normoglycemia, impaired fasting glucose (IFG), newly diagnosed T2DM, and established T2DM with durations of less than 5 years and 5 years or more. The primary endpoint was the incidence of all-cause dementia.

Results

Among 118,790 participants (average age 64.26 ± 9.95 years, 48% male), 16.7% developed dementia during an average follow-up of 7.3 ± 2.3 years. Participants with a history of T2DM for less than five years at cohort entry had a 26.7% higher risk of developing all-cause dementia compared to those with normoglycemia. Those with T2DM for five years or longer had a 46.7% increased risk, with an adjusted hazard ratio (aHR) of 1.466 (95% confidence interval [CI], 1.408–1.527). Specifically, the risk of developing Alzheimer's disease (AD) and vascular dementia (VaD) rose by 43.4% and 51.4%, respectively, for individuals with T2DM lasting more than five years (aHR 1.434, 95% CI 1.366–1.505; aHR 1.514, 95% CI 1.365–1.679, respectively).

Conclusions

Our findings demonstrated a significant association between an extended duration of T2DM and an increased risk of developing all-cause dementia, including AD and VaD in post-stroke population. These results emphasize proactive dementia prevention approaches in stroke survivors, particularly those with longstanding T2DM.

Introduction

The incidence of cognitive impairments following a stroke, notably Post-Stroke Cognitive Impairment and Post-Stroke Dementia (PSD), significantly contributes to the disability burden observed in post-stroke survivors [1,2,3,4]. This issue is increasingly prevalent in developed nations, where an aging population and healthcare advancements have led to reduced mortality but an elevated incidence of PSD [3]. Notably, PSD can develop independently of functional impairments poststroke, leading to considerable decreases in independence for daily activities [5]. Such conditions not only increase healthcare costs but also profoundly affect the quality of life for patients and their caregivers.

Given the clinical significance of PSD, identifying and modifying its risk factors is crucial, especially since direct preventive treatments are scarce. Therefore, the focus shifts to the understanding and addressing of risk factors [4, 6]. Known risk factors for PSD include age, educational level, stroke severity, post-stroke functional status, stroke lesion location, visible neuroimaging markers, vascular risks, and lifestyle factors [1, 3, 7,8,9]. Among these, type 2 diabetes mellitus (T2DM) has emerged as a key risk factor, increasing the risk of both stroke recurrence and PSD [1, 10, 11]. However, the nuanced relationship between prediabetes and PSD, as well as the role of T2DM duration in PSD risk, remains inadequately explored [10, 11]. As a vascular risk factor, T2DM may play a greater role in the development of vascular dementia, however, the differential impact of duration of T2DM on each type of dementia has not been fully understood [12].

Therefore, our study aimed to investigate the association between the duration of T2DM and the risk of developing dementia in individuals who have experienced acute stroke. To achieve this goal, we utilized data from the Korean National Health Insurance Service (K-NHIS) database, which encompasses the vast majority of the Korean population.

Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer’s disease

 

 Did your competent? doctor start doing something with this way back in 2003? NO? So, you DON'T have a functioning stroke doctor, do you?

Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain May 2003 

The latest here: 

Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer’s disease

• Gabriel L Ketron,
• Felix Grun,
• Joshua D Grill,
• Howard H Feldman,
• Robert A Rissman &
• Gregory J Brewer 

Alzheimer's Research & Therapy volume 17, Article number: 59 (2025) Cite this article

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Abstract

Background

Nicotinamide, a form of B3 vitamin, is an NAD⁺ precursor that reduces pTau₂₃₁ levels via histone deacetylase inhibition in murine models of Alzheimer’s disease (AD). A recent phase 2a randomized placebo-controlled trial tested high-dose oral nicotinamide for the treatment of early AD. While nicotinamide demonstrated good safety and tolerability, it did not significantly lower CSF pTau₂₃₁, the primary biomarker endpoint of the study. Characterization of nicotinamide’s pharmacokinetics and metabolites in the blood and CSF is needed.

Methods

In these post hoc, blinded analyses of plasma and CSF samples from the completed two-site placebo controlled randomized trial testing of 1500 mg PO BID oral nicotinamide, we used mass spectroscopy to measure nicotinamide and its inactive metabolite 1-methyl-nicotinamide in plasma at baseline, 6, and 12 months and in CSF at baseline and 12 months from 23 participants on drug and 24 on placebo.

Results

Pharmacokinetic analysis found mean 12 month plasma nicotinamide increased > 130-fold to 52 μM while mean methyl-nicotinamide increased > 600-fold to 91 μM in individuals receiving nicotinamide compared to those receiving placebo, whose levels were unchanged from baseline. However, CSF nicotinamide was only measurable in 6 of the 19 available participants (32%) (mean increase of at least 147-fold to 18 μM). These CSF nicotinamide concentrations were 66% of their plasma levels, indicating good CNS bioavailability in only some participants. In contrast to CSF nicotinamide, more treated participants had higher CSF methyl-nicotinamide (n = 9, 43 μM), suggesting high-dosage nicotinamide was sufficient to pass the blood–brain barrier, but 13 of 19 were metabolically inactivated. Treatment favorably decreased mean pTau₂₃₁ levels by 34% in those six participants with elevated CSF levels of nicotinamide, compared to 3% elevation in participants who did not have elevated CSF nicotinamide, and a 3% decrease for placebo. No such relationships were observed for total tau, pTau₁₈₁, or amyloid beta biomarkers.

Conclusions

Our findings suggest that oral administration markedly increased mean plasma nicotinamide levels, however CSF levels were below quantitation in a majority of participants and there was extensive metabolic inactivation to methyl-nicotinamide. Both the bioavailability and rapid metabolic methylation need to be addressed if nicotinamide is further developed as a potential intervention for AD.

Trial registration

NCT03061474, last updated 2023–10-17. https://clinicaltrials.gov/study/NCT03061474.

Background

Nicotinamide serves as a co-enzyme precursor to NAD⁺ and NADH for cellular oxidation–reduction reactions. Inhibition of class III histone deacetylases (HDAC Sirtuins) affects numerous therapeutic pathways including inducing PI3k, MAPK/ERK42/44, cAMP and NAD⁺ production pathways, associated with neuronal survival, autophagy, neuroplasticity and lower oxidative stress [1, 2]. In mouse models of Alzheimer’s disease (AD), nicotinamide improved cognitive function while lowering Aβ and soluble p-tau isoforms [1, 2]. In these studies, nicotinamide in the drinking water reduced pTau₂₃₁ in immunostained brain sections [1]. Sirt1 knockdown produced a similar effect suggesting nicotinamide inhibited the Sirt1 deacetylase. Nicotinamide also promotes NAD⁺ dependent sirtuin activity through increased NAD⁺ production.

Oral nicotinamide is absorbed in the small intestine and encounters some first pass metabolism in liver to inactive N-methyl-nicotinamide. Blood concentrations are also lowered by kidney filtration that may affect CNS bioavailability. For oral nicotinamide to be CNS active, it must penetrate the blood brain barrier without being inactivated [3]. Some reports indicate nicotinamide is transported across the blood brain barrier bidirectionally with non-saturable capacity [3], probably due to rapid phosphorylation. The phosphorylation of nicotinamide is mediated by nicotinamide phosphoribosyl transferase to make nicotinamide mononucleotide, which is rapidly converted by nicotinamide mononucleotide adenylyl transferase into NAD⁺ in the “two-step salvage pathway” [4]. NAD⁺ is reduced to NADH by dehydrogenases in the mitochondrial TCA cycle and oxidized back to NAD⁺ in the electron transport chain. Lastly, Sirt1, PARP and CD38 enzymes cut NAD⁺ by glycohydrolysis into nicotinamide and ADP-ribose [5]. Consumption and degradation pathways of nicotinamide in the gut microbiome, intestines, blood, and liver complicate drug delivery to the brain. Importantly, nicotinamide inhibition of sirtuins in cells is limited by its metabolism to 1-methyl-nicotinamide (methyl-nicotinamide hereafter) by nicotinamide N-methyl transferase [6]. These preclinical studies suggested a potential role for treating bioenergetic or acetylation deficits in AD and motivated a phase 2a proof-of-concept clinical trial.

The Nicotinamide as an Early AD Treatment (NEAT) study tested high-dose (1500 mg PO BID) oral nicotinamide in participants with Mild Cognitive Impairment (MCI) or mild dementia in whom a biomarker signature confirmed a diagnosis of AD. The primary outcome of the trial was change in CSF pTau₂₃₁ [7]. Soluble varieties of phosphorylated tau (pTau) at specific epitopes such as threonine 231 (pTau₂₃₁) and threonine 181 (pTau₁₈₁) are established markers of AD pathology in brain and serve as early biomarkers in the CSF [8].

In the NEAT trial, nicotinamide treatment of participants with MCI and mild AD dementia did not significantly reduce CSF pTau₂₃₁ compared to placebo [7]. There were non-significant trends toward reduced change in CSF pTau₁₈₁ and total tau with nicotinamide treatment. In the current study, we undertook post hoc analysis of nicotinamide pharmacokinetics (PK), pharmacodynamic (PD) metabolic inactivation to methyl-nicotinamide, and the association between nicotinamide concentration change and pTau₂₃₁ concentration changes using samples from the NEAT trial. These analyses were undertaken to address whether there were sufficient levels in plasma and CSF with this oral nicotinamide dosage in this study population over the 48-week treatment period. Furthermore, the PK/PD relationship of plasma and CSF levels of both nicotinamide and methyl metabolite were evaluated with change in pTau₂₃₁ and pTau₁₈₁ concentrations, and other Aβ biomarkers. To measure these metabolite concentrations, and the concentrations of various break-down products, we conducted a Liquid Chromatography Mass Spectrometry (LC/MS) study of all NEAT participant samples.

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Adherence and intensity in multimodal lifestyle-based interventions for cognitive decline prevention: state-of-the-art and future directions

 With your risk of dementia your competent? doctor and hospital better be closely following this. If not, I don't know what you have for stroke recovery and dementia prevention!

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018

5. Brain Bleeds Double Dementia Risk February 2025

The latest here:

Adherence and intensity in multimodal lifestyle-based interventions for cognitive decline prevention: state-of-the-art and future directions

• Natalia Soldevila-Domenech,
• Amaia Ayala-Garcia,
• Mariagnese Barbera,
• Jenni Lehtisalo,
• Laura Forcano,
• Ana Diaz-Ponce,
• Marissa Zwan,
• Wiesje M. van der Flier,
• Tiia Ngandu,
• Miia Kivipelto,
• Alina Solomon &
• Rafael de la Torre 

Alzheimer's Research & Therapy volume 17, Article number: 61 (2025) Cite this article

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Abstract

Preventing dementia and Alzheimer’s disease (AD) is a global priority. Multimodal interventions targeting several risk factors and disease mechanisms simultaneously are currently being tested worldwide under the World-Wide FINGERS (WW-FINGERS) network of clinical trials. Adherence to these interventions is crucial for their success, yet there is significant heterogeneity in adherence reporting across studies, hindering the understanding of adherence barriers and facilitators. This article is a narrative review of available evidence from multimodal dementia prevention trials. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: nonpharmacological multimodal interventions (i.e., combining three or more intervention domains), targeting individuals without dementia, and using changes in cognitive performance and/or incident mild cognitive impairment or dementia as primary outcomes. Based on the findings, we propose future adherence reporting to encompass both participation (average attendance to each intervention component) and lifestyle change using dementia risk scores (e.g., the LIBRA index). Moreover, we provide an estimation of the expected intensity of multimodal interventions, defined as the ratio of the expected dose (i.e., the overall amount of the intervention offered specified in the trial protocol) to duration (in months). Adjusting the expected dose by average adherence enables estimation of the observed dose and intensity, which could be informative for identifying optimal dosage thresholds that maximize cognitive benefits across different populations. Finally, this article provides an overview of the determinants of adherence to multimodal interventions, emphasizing the need for improved adherence reporting to inform the design and implementation of precision prevention interventions.

Background

Alzheimer’s disease (AD), the most prevalent cause of dementia, develops over a long preclinical period and its progression is associated with modifiable lifestyle factors [1, 2]. This offers a window of opportunity for testing early preventive measures. In the last decade, there has been a shift toward multimodal lifestyle-based interventions for dementia prevention (e.g., combining diet, physical activity, cognitive training, vascular risk monitoring, or social interaction), due to the multifactorial nature of this condition [3]. In contrast to interventions targeting one risk factor alone, multimodal interventions target multiple risk factors simultaneously and are expected to generate additive or synergistic preventive effects. However, there is still limited evidence on the effectiveness of multimodal interventions for the prevention of cognitive decline [4]. Additionally, uncertainties persist regarding barriers and facilitators of adherence and response to multimodal interventions, modes of intervention delivery, and the intervention intensity (dose, duration, and adherence) required to influence cognitive performance [5]. Addressing these questions is crucial for advancing and optimizing multimodal interventions for dementia prevention, both at the individual (i.e., personalized prevention), and population levels (i.e., precision prevention) [6, 7].

The effectiveness of a next generation of precision prevention interventions for cognitive decline will rely on how effectively preventive programs are provided to populations of interest, their ability to adhere to such interventions, and the ability of healthcare providers to monitor adherence and adjust the intervention as needed. Adherence is recognized as the strongest predictor of intervention success [8]. However, there is a paucity of studies addressing the determinants of adherence to multimodal interventions [9,10,11,12,13,14]. This gap in evidence is, in part, attributed to the absence of a gold standard definition of adherence to these complex multimodal interventions. Although a single definition may not universally apply to all studies, the development of consensus-based recommendations for measuring and reporting adherence to multimodal interventions could enhance consistency across studies and thus establish global standards for conducting comparative effectiveness research. This is particularly important in the framework of international collaborative networks conducting multimodal intervention trials aimed at preventing cognitive decline, e.g., the World-Wide FINGERS (WW-FINGERS) network [15]. Harmonizing measures of adherence to multimodal interventions will facilitate pooled analyses, which are crucial for providing robust evidence about adherence profiles and progressing in AD prevention research.

The aim of this narrative review is to provide an overview of the available evidence on adherence and efficacy from multimodal dementia prevention trials.

More at link.

Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

 Just maybe you've rediscovered Capillaries that don't open due to pericytes September 2011. What the fuck is your solution to that problem? Describing a problem with NO solution is grounds for firing! My God, the amount of absolute stupidity in stroke is appalling!

Hypoperfusion is a term that describes "a reduced amount of blood flow".

Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

Samantha Rivet, MDCM https://orcid.org/0000-0001-6099-237X, Leonid Churilov, PhD https://orcid.org/0000-0002-9807-6606, Nawaf Yassi, MBBS, PhD https://orcid.org/0000-0002-0685-0060, Timothy J. Kleinig, MBBS(Hons), PhD https://orcid.org/0000-0003-4430-3276, Vincent Thijs, MD, PhD https://orcid.org/0000-0002-6614-8417, Teddy Wu, MBChB, PhD https://orcid.org/0000-0003-1845-1769, Helen Dewey, MBBS, PhD https://orcid.org/0000-0001-9484-2070, … Show All … , and Felix Chun Ng, MBBS, PhD https://orcid.org/0000-0001-6973-8677 ng.f@unimelb.edu.auAuthor Info & Affiliations

Stroke

New online

https://doi.org/10.1161/STROKEAHA.124.049574

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Abstract

BACKGROUND:

Tissue-level hypoperfusion (no-reflow) persists in 30% of patients with seemingly successful upstream angiographic recanalization at thrombectomy. We investigated the clinical impact of the no-reflow phenomenon by comparing patients with no-reflow versus patients with varying degrees of angiographic recanalization.

METHODS:

In a post hoc pooled analysis of the EXTEND-IA (Endovascular Therapy for Ischemic Stroke With Perfusion-Imaging Selection) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke) part 1 and 2 trials, clinical and radiological outcomes were compared between patients with (1) full angiographic recanalization with no-reflow (expanded Treatment in Cerebral Ischemia [eTICI] 2c3–NoReflow), defined as >15% reduction in relative cerebral blood flow or Volume within the infarct relative to a contralateral homolog on 24-hour-follow-up perfusion computed tomography or magnetic resonance imaging despite eTICI grade 2c-3 angiographic recanalization, (2) full angiographic recanalization and tissue reperfusion (eTICI 2c3–CompleteFlow), (3) partial angiographic recanalization (eTICI 2b), and (4) unsuccessful thrombectomy (eTICI 0-2a). The primary outcome, functional independence at 90 days, was investigated using a mixed effect logistic regression model, both unadjusted and adjusted for a priori-selected covariates, namely age, premorbid modified Rankin Scale, baseline National Institutes of Health Stroke Scale, and baseline core volume.

RESULTS:

Among 537 patients from the overall pooled cohort, 456 patients were included in the analysis. The mean age of the included patients was 71 years old, and 54% were male. A favorable outcome (90-day modified Rankin Scale score of 0–2 or return to baseline modified Rankin Scale) was observed in 43.33% (n=13/30) of patients with eTICI 2c3–NoReflow, 67.50% (n=81/120) of eTICI 2c3–CompleteFlow, 63.03% (n=150/238) of eTICI 2b, and 50.00% (n=34/68) of unsuccessful thrombectomy. In multivariable analysis, patients with eTICI 2c3–NoReflow had lower odds of favorable outcome compared with those with eTICI 2c3–CompleteFlow (adjusted odds ratio, 0.31 [95% CI, 0.12–0.77]; P=0.01) and eTICI 2b (adjusted odds ratio, 0.40 [95% CI, 0.17–0.96]; P=0.04) but not unsuccessful thrombectomy (adjusted odds ratio, 1.02 [95% CI, 0.38–2.73]; P=0.97). Patients with eTICI 2c3–NoReflow had similar follow-up infarct volume to unsuccessful thrombectomy (β=−8.26 [95% CI, −27.38 to 10.86]; P=0.40) and eTICI 2b (β=9.38 [95% CI, −7.33 to 26.09]; P=0.27) but had larger infarcts compared with eTICI 2c3–CompleteFlow (β=18.85 [95% CI, 1.16–36.54]; P=0.04).

CONCLUSIONS:

When no-reflow occurred, clinical and radiological outcomes in patients with full angiographic recanalization were similar to patients with unsuccessful thrombectomy. Preventing or reversing no-reflow has the potential to augment the clinical benefit of reperfusion treatment in ischemic stroke.

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Approved Cancer Drugs May Have Potential to Treat Hemorrhagic Stroke

 Are your stroke medical 'professionals' ensuring this research gets completed? NO? 

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

Approved Cancer Drugs May Have Potential to Treat Hemorrhagic Stroke

tony Brook pathology researcher’s work supported by a $2.6 million NIH grant

STONY BROOK, NY, March 31, 2025 – There is currently no effective drug to treat a hemorrhagic stroke, when a ruptured blood vessel causes bleeding into the brain. Researcher Ke Jian Liu, PhD, however, believes that a drug treatment for hemorrhagic stroke may emerge by way of repurposing certain drugs that are already Food and Drug Administration (FDA) approved to treat cancer. His approach and experiments are supported by a five-year $2.6 million grant from the National Institute of Neurological Disorders and Stroke, a branch of the National Institutes of Health (NIH). The grant runs through November 2029.

According to the American Stroke Association, hemorrhagic strokes account for approximately 13 percent of stroke cases. One form of this type of stroke causes blood bleeds within the brain (intracerebral hemorrhage). Overall, stroke is a leading cause of disability to Americans and the fifth leading cause of death.

Ke Jian Liu, PhD, Professor of Pathology and research scientist
Credit: Jeanne Neville, Stony Brook Medicine

Liu’s research is based on his discovery of a novel mechanism related to processes of zinc in the blood and brain, which is affected by a class of cancer drugs called protein kinase inhibitors.

Despite extensive research, the mechanisms of intracerebral hemorrhage-induced brain damage are not well understood. This damage is thought to be mediated through red cell lysis and toxicity of released hemoglobin and its degradation products, heme and free iron. But therapeutic strategies on hemoglobin, heme, iron and other blood components in edema formation have fallen short. Liu’s lab uncovered that endogenously formed zinc protoporphyrin (ZnPP), a complex in red blood cells made up of the compound porphyrin and complexes of zinc, contributes to intracerebral hemorrhage-induced brain damage.

“We think that this discovery opens new avenues for drug therapeutic intervention to treat hemorrhagic stroke,” says Liu, Professor in the Department of Pathology in the Renaissance School of Medicine at Stony Brook University, and Associate Director of Basic Science in the Stony Brook University Cancer Center.

He and colleagues are targeting the formation of ZnPP in the brain. Their initial findings with a selected compound inhibitor that connects to ZnPP demonstrated that protein kinase inhibitors can reduce brain injury and improve neurological outcomes in animal models of hemorrhagic stroke.

“Essentially, we conduct experiments in models of hemorrhagic stroke to investigate the mechanisms underlying ZnPP generation and neurotoxicity,” says Liu.

He points out that the FDA-approved cancer drugs do not inhibit ZnPP, and that he and his team reached their hypothesis and conclusion through research taking several steps.

First, his lab discovered that ZnPP is generated during hemorrhagic stroke and that ZnPP is more neurotoxic than any other known compounds involved in stroke brain injury. Second, since ZnPP is known to be generated via an enzyme called ferrochelatase, Liu and colleagues tested and found that inhibiting ferrochelatase does decrease ZnPP generation and reduce brain injury following stroke. And third, they searched for clinically applicable ferrochelatase inhibitors. They centered on kinase inhibitors, which possess off-target effects on ferrochelatase not related to cancer treatments.

“We connected the dots and began testing some FDA-approved kinase inhibitors, which validated our speculation with ferrochelatase. So now we are exploring the potential of pharmacologically inhibiting ZnPP generation by investigating off-target ferrochelatase inhibition using these inhibitors,” explains Liu.

To date, the FDA has approved 82 small-molecule protein kinase inhibitors for treating a variety of cancers, including leukemia, lymphoma, and breast cancer. This provides many options for Liu and colleagues to test multiple kinase inhibitors in relation to inhibiting ferrochelatase and to compare the results.

Liu thinks that the research could potentially transform stroke researchers’ understanding of intracerebral hemorrhage-induced brain injury and ultimately provide a new treatment for hemorrhagic stroke.

He and fellow investigators believe that if the treatment approach continues to prove to be effective, safe, and improve outcomes after hemorrhagic stroke in their experimental models, proposals for human trials could progress quickly, given that drug toxicity studies would not be required because of the FDA-approved status that already exists with the inhibitors.