Remote ischaemic conditioning: defining critical criteria for success—report from the 11th Hatter Cardiovascular Workshop

Bell, R. M.; Basalay, M.; Bøtker, H. E.; Beikoghli Kalkhoran, S.; Carr, R. D.; Cunningham, J.; Davidson, S. M.; England, T. J.; Giesz, S.; Ghosh, A. K.; Golforoush, P.; Gourine, A. V.; Hausenloy, D. J.; Heusch, G.; Ibanez, B.; Kleinbongard, P.; Lecour, S.; Lukhna, K.; Ntsekhe, M.; Ovize, M.; Salama, A. D.; Vilahur, G.; Walker, J. M.; Yellon, D. M.

doi:10.1007/s00395-022-00947-2

Effect of Proximal Blood Flow Arrest During Endovascular Thrombectomy (ProFATE): a multicentre, blinded-endpoint, randomised clinical trial (2024)
Journal Article
Dhillon, P. S., Butt, W., Podlasek, A., Bhogal, P., Lynch, J., Booth, T. C., McConachie, N., Lenthall, R., Nair, S., Malik, L., Goddard, T., Carraro Do Nascimento, V., Barrett, E., Jethwa, K., Krishnan, K., Dineen, R. A., & England, T. J. (in press). Effect of Proximal Blood Flow Arrest During Endovascular Thrombectomy (ProFATE): a multicentre, blinded-endpoint, randomised clinical trial. Stroke,

Background
The effect of temporary blood flow arrest during endovascular thrombectomy (EVT) for acute ischaemic stroke (AIS) is uncertain due to the lack of evidence from randomised controlled trials (RCT). We aimed to investigate whether temporary... Read More about Effect of Proximal Blood Flow Arrest During Endovascular Thrombectomy (ProFATE): a multicentre, blinded-endpoint, randomised clinical trial.

Pre‐hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT‐2 trial (2024)
Journal Article
Appleton, J. P., Dixon, M., Woodhouse, L. J., Anderson, C. S., Ankolekar, S., Cala, L., England, T. J., Godolphin, P. J., Krishnan, K., Mair, G., Muir, K. W., Potter, J., Price, C. I., Randall, M., Robinson, T. G., Roffe, C., Rothwell, P. M., Sandset, E. C., Saver, J. L., Siriwardena, A. N., …Bath, P. M. (2024). Pre‐hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT‐2 trial. European Journal of Neurology, 31(12), Article e16502. https://doi.org/10.1111/ene.16502

Background and purpose
Ambulance trials assessing interventions in suspected stroke patients will recruit patients with currently active symptoms that will resolve into transient ischaemic attack (TIA). The safety and efficacy of glyceryl trinitrate... Read More about Pre‐hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT‐2 trial.

Endovascular thrombectomy vs best medical management for late presentation acute ischaemic stroke with large vessel occlusion without CT perfusion or MR imaging selection: A systematic review and meta-analysis (2024)
Journal Article
Dhillon, P. S., Marei, O., Podlasek, A., Butt, W., Rice, H., de Villiers, L., Carraro do Nascimento, V., McConachie, N., Lenthall, R., Nair, S., Malik, L., Bhogal, P., Dineen, R. A., & England, T. J. (2024). Endovascular thrombectomy vs best medical management for late presentation acute ischaemic stroke with large vessel occlusion without CT perfusion or MR imaging selection: A systematic review and meta-analysis. Journal of Stroke and Cerebrovascular Diseases, 33(11), Article 108002. https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.108002

Background The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from stroke onset for patients with large vessel occlusion (LVO) selected without CT perfusion(CTP) or MR imaging(MRI) is undeterm... Read More about Endovascular thrombectomy vs best medical management for late presentation acute ischaemic stroke with large vessel occlusion without CT perfusion or MR imaging selection: A systematic review and meta-analysis.

The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial (2024)
Journal Article
Hollingworth, M., Woodhouse, L. J., Law, Z. K., Ali, A., Krishnan, K., Dineen, R. A., Christensen, H., England, T. J., Roffe, C., Werring, D., Peters, N., Ciccone, A., Robinson, T., Członkowska, A., Bereczki, D., Egea-Guerrero, J. J., Ozturk, S., Bath, P. M., & Sprigg, N. (2024). The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial. Neurosurgery, 95(3), 605-616. https://doi.org/10.1227/neu.0000000000002961

BACKGROUND AND OBJECTIVES:
An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hemato... Read More about The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial.

Remote Ischemic Conditioning for Secondary Stroke Prevention: Time for a Clinical Trial? (2024)
Journal Article
Nadareishvili, Z., Bath, P. M., & England, T. J. (2024). Remote Ischemic Conditioning for Secondary Stroke Prevention: Time for a Clinical Trial?. Neurology, 102(7), Article e208072. https://doi.org/10.1212/WNL.0000000000208072

Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials (2023)
Journal Article
Krishnan, K., Campos, P. B., Nguyen, T. N., Tan, C. W., Chan, S. L., Appleton, J. P., Law, Z., Hollingworth, M., Kirkman, M. A., England, T. J., Roffe, C., Macleod, M. J., Dawson, J., Bayraktutan, U., Werring, D. J., Sprigg, N., & Bath, P. M. (2023). Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials. Frontiers in Stroke, 2, Article 1256664. https://doi.org/10.3389/fstro.2023.1256664

Acute intracerebral hemorrhage is the most devastating stroke subtype and is associated with significant morbidity and mortality. Poor prognosis is associated with primary brain injury from the presenting hematoma, and despite advances in clinical tr... Read More about Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials.

Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia (2023)
Journal Article
Woodhouse, L. J., Appleton, J. P., Christensen, H., Dineen, R. A., England, T. J., James, M., Krishnan, K., Montgomery, A. A., Ranta, A., Robinson, T. G., Sprigg, N., & Bath, P. M. (2023). Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia. Scientific Reports, 13, Article 11717. https://doi.org/10.1038/s41598-023-38474-2

Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase th... Read More about Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia.

Remote ischemic conditioning for stroke: A critical systematic review (2023)
Journal Article
Keevil, H., Phillips, B. E., & England, T. J. (in press). Remote ischemic conditioning for stroke: A critical systematic review. International Journal of Stroke, 19(3), 271-279. https://doi.org/10.1177/17474930231191082

Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasi... Read More about Remote ischemic conditioning for stroke: A critical systematic review.

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): effects on outcomes at day 365 in a randomised, sham-controlled, blinded, phase III, superiority ambulance-based trial (2023)
Journal Article
Woodhouse, L. J., Appleton, J. P., Ankolekar, S., England, T. J., Mair, G., Muir, K., Price, C. I., Pocock, S., Randall, M., Robinson, T. G., Roffe, C., Sandset, E. C., Saver, J. L., Siriwardena, A. N., Sprigg, N., Wardlaw, J. M., & Bath, P. M. (2023). Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): effects on outcomes at day 365 in a randomised, sham-controlled, blinded, phase III, superiority ambulance-based trial. BMJ Neurology Open, 5(1), Article e000424. https://doi.org/10.1136/bmjno-2023-000424

Background The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2) reported no overall treatment difference between glyceryl trinitrate (GTN) and sham at day 90. Here we assess participants' outcomes 1 year after rand... Read More about Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): effects on outcomes at day 365 in a randomised, sham-controlled, blinded, phase III, superiority ambulance-based trial.

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: A secondary analysis of a large randomised controlled trial (2023)
Journal Article
Appleton, J. P., Kang, Z., Woodhouse, L. J., Al-Shahi Salman, R., Beridze, M., Christensen, H., Dineen, R. A., Egea-Guerrero, J. J., England, T. J., Karlinski, M., Krishnan, K., Laska, A. C., Lyrer, P. A., Ozturk, S., Roffe, C., Roberts, I., Robinson, T. G., Scutt, P., Werring, D. J., Bath, P. M., & Sprigg, N. (2023). Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: A secondary analysis of a large randomised controlled trial. BMJ Neurology Open, 5(1), Article e000423. https://doi.org/10.1136/bmjno-2023-000423

Background Tranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statist... Read More about Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: A secondary analysis of a large randomised controlled trial.

Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial (2023)
Journal Article
Appleton, J. P., Woodhouse, L. J., Anderson, C. S., Ankolekar, S., Cala, L., Dixon, M., England, T. J., Krishnan, K., Mair, G., Muir, K. W., Potter, J., Price, C. I., Randall, M., Robinson, T. G., Roffe, C., Sandset, E. C., Saver, J. L., Shone, A., Siriwardena, A. N., Wardlaw, J. M., …Bath, P. M. (2023). Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial. Stroke and Vascular Neurology, 9(1), https://doi.org/10.1136/svn-2022-001634

Background The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespeci... Read More about Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial.

Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial (2023)
Journal Article
Wardlaw, J. M., Woodhouse, L. J., Mhlanga, I. I., Oatey, K., Heye, A. K., Bamford, J., Cvoro, V., Doubal, F. N., England, T., Hassan, A., Montgomery, A., O’Brien, J. T., Roffe, C., Sprigg, N., Werring, D. J., & Bath, P. M. (2023). Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial. JAMA Neurology, 80(7), 682-692. https://doi.org/10.1001/jamaneurol.2023.1526

Importance Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), is the most common cause of vascular cognitive impairment, and impairs mobility and mood but has no specific treatment.

Objective To test the feasibili... Read More about Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial.

Endovascular Thrombectomy Versus Best Medical Management Beyond 24 Hours From Last Known Well in Acute Ischemic Stroke Due to Large Vessel Occlusion (2023)
Journal Article
Dhillon, P. S., Butt, W., Jovin, T. G., Podlasek, A., McConachie, N., Lenthall, R., Nair, S., Malik, L., Krishnan, K., Dineen, R. A., & England, T. J. (2023). Endovascular Thrombectomy Versus Best Medical Management Beyond 24 Hours From Last Known Well in Acute Ischemic Stroke Due to Large Vessel Occlusion. Stroke: Vascular and Interventional Neurology, 3(5), Article e000790. https://doi.org/10.1161/svin.122.000790

BACKGROUND
The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined.

METHODS
In this single center... Read More about Endovascular Thrombectomy Versus Best Medical Management Beyond 24 Hours From Last Known Well in Acute Ischemic Stroke Due to Large Vessel Occlusion.

Comparison Between In‐Hospital and Community‐Onset Stroke Treated With Endovascular Thrombectomy: A Propensity Score–Matched Cohort Study (2023)
Journal Article
Dhillon, P. S., Soo, E., Butt, W., Nguyen, T. N., Barrett, E., Podlasek, A., McConachie, N., Lenthall, R., Nair, S., Malik, L., Cheema, C., Bhogal, P., Makalanda, H. L. D., James, M. A., Dineen, R. A., & England, T. J. (2023). Comparison Between In‐Hospital and Community‐Onset Stroke Treated With Endovascular Thrombectomy: A Propensity Score–Matched Cohort Study. Stroke: Vascular and Interventional Neurology, 3(4), Article e000816. https://doi.org/10.1161/svin.122.000816

Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial (2023)
Journal Article
Dhillon, P. S., Butt, W., Podlasek, A., Bhogal, P., McConachie, N., Lenthall, R., Nair, S., Malik, L., Lynch, J., Goddard, T., Barrett, E., Krishnan, K., Dineen, R. A., & England, T. J. (2023). Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial. European Stroke Journal, 8(2), 581-590. https://doi.org/10.1177/23969873231166194

Background: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-lev... Read More about Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial.

Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke (2023)
Journal Article
Dhillon, P. S., Butt, W., Marei, O., Podlasek, A., McConachie, N., Lenthall, R., Nair, S., Malik, L., Bhogal, P., Makalanda, H. L. D., Dineen, R. A., & England, T. J. (2023). Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke. Journal of Stroke and Cerebrovascular Diseases, 32(5), Article 107083. https://doi.org/10.1016/j.jstrokecerebrovasdis.2023.107083

Background: Numerous ischaemic stroke patients experience poor functional outcome despite successful recanalisation following endovascular thrombectomy (EVT). We aimed to identify the incidence and predictors of futile complete recanalisation (FCR) i... Read More about Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke.

Antiplatelet Resistance: A Review of Concepts, Mechanisms, and Implications for Management in Acute Ischemic Stroke and Transient Ischemic Attack (2023)
Journal Article
Krishnan, K., Nguyen, T. N., Appleton, J. P., Law, Z. K., Caulfied, M., Cabrera, C. P., Lenthall, R., Hewson, D., England, T., McConachie, N., Dhillon, P., Malik, L., Podlasek, A., Smith, C. J., Dawson, J., Robinson, T. G., Sprigg, N., James, M. A., White, P., Desborough, M. J., …Bath, P. M. (2023). Antiplatelet Resistance: A Review of Concepts, Mechanisms, and Implications for Management in Acute Ischemic Stroke and Transient Ischemic Attack. Stroke: Vascular and Interventional Neurology, 3(3), Article e000576. https://doi.org/10.1161/svin.122.000576

Acute ischemic stroke is a leading cause of death and major disability worldwide. Approximately 50% of ischemic strokes are caused by atherothrombotic occlusion of the cerebral arteries, and antiplatelets are the mainstay of secondary stroke preventa... Read More about Antiplatelet Resistance: A Review of Concepts, Mechanisms, and Implications for Management in Acute Ischemic Stroke and Transient Ischemic Attack.

Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts (2022)
Journal Article
Singh Dhillon, P., Butt, W., Jovin, T. G., Podlasek, A., McConachie, N., Lenthall, R., Nair, S., Malik, L., Krishnan, K., Chiavacci, I., Mehedi, F., Hong, T., Selva, H., Dineen, R. A., & England, T. J. (2023). Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts. Stroke: Vascular and Interventional Neurology, 3(2), Article e000686. https://doi.org/10.1161/SVIN.122.000686

Background: The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from acute ischaemic stroke (AIS) onset for patients selected without CT perfusion or MR imaging is undetermined in routine clinical practice.

Methods: In this... Read More about Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts.

Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter)-a randomised placebo-controlled feasibility trial (2022)
Journal Article
Bath, P. M., Skinner, C. J. C., Bath, C. S., Woodhouse, L. J., Areti, A., Korovesi, K., Long, H., Havard, D., Coleman, C. M., England, T. J., Leyland, V., Lim, W. S., Montgomery, A. A., Royal, S., Avery, A., Webb, A. J., & Gordon, A. L. (2022). Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter)-a randomised placebo-controlled feasibility trial. European Geriatric Medicine, 13, 1343-1355. https://doi.org/10.1007/s41999-022-00714-5

Purpose
Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in ca... Read More about Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter)-a randomised placebo-controlled feasibility trial.

Remote ischaemic conditioning: defining critical criteria for success—report from the 11th Hatter Cardiovascular Workshop (2022)
Journal Article
Bell, R. M., Basalay, M., Bøtker, H. E., Beikoghli Kalkhoran, S., Carr, R. D., Cunningham, J., Davidson, S. M., England, T. J., Giesz, S., Ghosh, A. K., Golforoush, P., Gourine, A. V., Hausenloy, D. J., Heusch, G., Ibanez, B., Kleinbongard, P., Lecour, S., Lukhna, K., Ntsekhe, M., Ovize, M., …Yellon, D. M. (2022). Remote ischaemic conditioning: defining critical criteria for success—report from the 11th Hatter Cardiovascular Workshop. Basic Research in Cardiology, 117, Article 39. https://doi.org/10.1007/s00395-022-00947-2

The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from th... Read More about Remote ischaemic conditioning: defining critical criteria for success—report from the 11th Hatter Cardiovascular Workshop.

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