Predicting Long-Term Outcome after Endovascular Stroke Treatment: The Totaled Health Risks in Vascular Events Score

Background and Purpose: High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. Methods: We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70% or greater according to OPA after 10 μM ADP stimuli. Results: The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3% (109/968). Its rate was significantly higher in the patients with HRPR (16.7%) than in those without (9.7%). HPRP was independently associated with the primary endpoint (OR=1.97, CI 1.22 to 3.18, p<0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR=2.26, CI 1.15 to 4.45, P=0.02). Conclusions: In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.

Download Full-text

Genetic Aspects of Inflammation and Immune Response in Stroke

International Journal of Molecular Sciences ◽

10.3390/ijms21197409 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7409

Author(s):

Dejan Nikolic ◽

Milena Jankovic ◽

Bojana Petrovic ◽

Ivana Novakovic

Keyword(s):

Immune Response ◽

Brain Plasticity ◽

Treatment Modalities ◽

Genetic Determinants ◽

Term Outcome ◽

Long Term Outcome ◽

Stroke Treatment ◽

Complex Processes ◽

Non Coding Rnas

Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of candidate genes, such as IL-6, BDNF, COX2, CYPC19, and GPIIIa could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in genesPATJ and LOC as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation.

Download Full-text

Long-term outcome after aneurysmal subarachnoid hemorrhage—risks of vascular events, death from cancer and all-cause death

Journal of Neurology ◽

10.1007/s00415-013-7192-8 ◽

2013 ◽

Vol 261 (2) ◽

pp. 309-315 ◽

Cited By ~ 13

Author(s):

Dennis J. Nieuwkamp ◽

Arno de Wilde ◽

Marieke J. H. Wermer ◽

Ale Algra ◽

Gabriël J. E. Rinkel

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Vascular Events ◽

Term Outcome ◽

Long Term Outcome

Download Full-text

Stroke treatment in Stroke Unit: from scientific evidences to clinical practice

Italian Journal of Medicine ◽

10.4081/itjm.2009.239 ◽

2013 ◽

pp. 239-243

Author(s):

Michele Stornello ◽

Filomena Pietrantonio

Keyword(s):

Early Stage ◽

Integrated Approach ◽

Stroke Care ◽

Term Outcome ◽

Long Term Outcome ◽

Stroke Treatment ◽

Care Approach ◽

Long Term Follow Up ◽

Set Up

Background: In themanagement of stroke disease, evidences fromthe literature demonstrate that the introduction of stroke units, hospital wards with dedicated beds providing intensive care within 48 hours of symptoms’ onset, produced a real improvement in the outcome, reducing in-hospital fatality cases and increasing the proportion of patients independently living in long term follow-up. Discussion: The article focuses on stroke disease-management, suggesting a stroke integrated approach for the admission of patients on dedicated beds, in order to extend the ‘‘stroke care’’ approach outcomes to as many hospitals as possible in Italy. This approach implies the set up of a stroke network for an effective patients’ stratification according to the severity of the illness at debut; the set up of an integrated team of specialists in hospital management of the acute phase (first 48 hours) and a timely rehabilitation treatment. Ultimately the hospital should be organized according to department’s semi-intensive areas in order to assure to the patients, in the early stage of the disease, a timely high intensity care aimed to improve the long term outcome.

Download Full-text

Long-term neurological, vascular, and mortality outcomes after stroke

International Journal of Stroke ◽

10.1177/1747493018798526 ◽

2018 ◽

Vol 13 (8) ◽

pp. 787-796 ◽

Cited By ~ 11

Author(s):

Ravinder-Jeet Singh ◽

Shuo Chen ◽

Aravind Ganesh ◽

Michael D Hill

Keyword(s):

Acute Stroke ◽

Recurrent Stroke ◽

Intravenous Thrombolysis ◽

Stroke Recurrence ◽

Stroke Survivors ◽

Acute Stroke Care ◽

Term Outcome ◽

Long Term Outcome ◽

Stroke Treatment

Background Despite improved survival and short-term (90-day) outcomes of ischemic stroke patients, only sparse data exist describing the sustained benefits of acute stroke care interventions and long-term prognosis of stroke survivors. Aim We review the contemporary literature assessing long-term (5 years or more) outcomes after stroke and acute stroke treatment. Summary of review Acute stroke unit care and intravenous thrombolysis have sustained benefits over longer follow-up, but few data exist on the long-term outcome after endovascular thrombectomy (EVT). A large proportion of stroke survivors face challenges of residual disability and neuropsychiatric sequelae (especially affective disorders and epilepsy) which affects their quality of life and is associated with poorer prognosis due to increase in stroke recurrences/mortality. Nearly, a quarter of stroke survivors have a recurrent stroke at 5 years, and nearly double that at 10 years. Mortality after recurrent stroke is high, and half of the stroke survivors are deceased at 5 years after stroke and three fourth at 10 years. Long-term all-cause mortality is largely due to conditions other than stroke. Both stroke recurrence and long-term mortality are affected by several modifiable risk factors, and thus amenable to secondary prevention strategies. Conclusions There is a need for studies reporting longer term effects of acute interventions, especially EVT. Better preventive strategies are warranted to reduce the vascular and non-vascular mortality long after stroke.

Download Full-text

Long-Term Outcome in Polycythemia Vera (PV): Final Analysis of a Randomized Trial Comparing Hydroxyurea (HU) to Pipobroman (Pi).

Blood ◽

10.1182/blood.v112.11.1746.1746 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1746-1746 ◽

Cited By ~ 6

Author(s):

Jean-Jacques Kiladjian ◽

Sylvie Chevret ◽

Christine Dosquet ◽

Pierre Fenaux ◽

Christine Chomienne ◽

...

Keyword(s):

Median Survival ◽

Cumulative Incidence ◽

Randomized Clinical Trials ◽

Final Analysis ◽

Vascular Events ◽

Term Outcome ◽

Long Term Outcome ◽

Mortality And Morbidity

Abstract Background: Only 4 randomized clinical trials in PV have directly compared cytoreductive therapies (32P, busulfan, chlorambucil, HU, and Pi), all published after a median follow-up of 10 years or less. Thrombosis was the main cause of mortality and morbidity in all trials. Cumulative incidence of evolution to myelofibrosis (MF), and acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) was about 8%, and 6%, respectively. In 1 of those trials, conducted between 1980 and 1996 by the French Polycythemia Study Group (FPSG) in 292 PV patients (pts) younger than 65 yrs, no difference between HU and Pi was found in terms of survival, risk of thrombosis, and AML/MDS/MF evolution at the time of first analysis with a median follow up of 7 years (Najean, Blood, 1997, 90:3370). Methods: We updated the results of the FPSG trial at the reference date of April 15, 2008, with a median follow-up of 16.3 years. After randomization in the trial (136 pts in the HU arm, 149 in the Pi arm), 94 (33%) pts had received only HU, 130 (46%) only Pi, and 61 (21%) both drugs (including 42 who had switched from HU to Pi, and 19 from Pi to HU) during the whole follow-up period (7 patients were excluded from the final analysis because of incomplete follow up data). To take into account treatment crossovers, statistical analysis was performed both in “intention to treat” (ITT) and according to the main treatment received (i.e. treatment effectively received). Results: Median survival was 20.3 years (95%CI: 16.4 – 25) in HU arm, and 15.4 years (95%CI: 13.4 – 17) in Pi arm (p=0.008). 95 pts have died, the 3 main causes of death being evolution to AML/MDS in 51 pts (54%), vascular events in 19 pts (20%), and solid tumor in 11 (12%) pts. The 51 cases of evolution to AML/MDS included 10 MDS, and 41 AML (including 5 preceded by an MDS phase). Cumulative incidence (CI) of AML/MDS at 10, 15, and 20 years in ITT analysis was 6.6%, 16.5%, and 24% in the HU arm, and 13%, 34%, and 52% in the Pi arm, respectively (p= 0.004). As the median duration of HU treatment (12 years) was significantly longer than that of Pi treatment (9.5 years, p=0.0002), we also performed the analyses according to the main treatment actually received by pts, which showed cumulative incidence of AML/MDS of 7%, 14%, and 22% with HU, and 12%, 37%, and 56% with Pi at 10, 15, and 20 years, respectively (p=0.008), confirming the results obtained in ITT analyses. Regarding MF, the CI at 10, 15 and 20 years was comparable in both arms in ITT analysis: 12.6%, 19%, and 27% in the HU arm, and 7.8%, 16%, and 27% in the Pi arm, respectively (p=0.7). However, a significantly higher incidence of MF was found in pts who had received HU as main treatment: 15%, 24%, and 32% at 10, 15, and 20 years, compared to 5%, 10%, and 21%, respectively, in patients who received mainly Pi (p=0.02). Conclusion: Although medium-term analysis of FPSG trial did not show differences between HU and Pi, current update after a median follow-up of 16.3 years finally showed that median survival was shorter, and incidence of AML/MDS higher in Pi treated pts. By contrast, risk of MF was higher in pts treated predominantly with HU. Of note, was the clearly higher than previously reported cumulative incidence of AML/MDS with HU. Evolution to AML/MDS represented by far the first cause of death in the long-term (54% versus 20% for vascular events). Those results suggest that Pi should not be used as first line therapy in PV patients, and that very long term may be required to draw conclusions regarding leukemic evolution in PV trials.

Download Full-text