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Bakola E, Palaiodimou L, Kargiotis O, Safouris A, Psychogios K, Karapanayiotides T, Moschovos C, Sharma VK, Rubin MN, Freitas JS, Baracchini C, Krogias C, Alexandrov AV, Georgios T. Microembolic signal detection in acute ischemic stroke: Clinical relevance and impact on treatment individualization-A narrative review. Eur J Neurol 2025; 32:e16584. [PMID: 39706201 DOI: 10.1111/ene.16584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 11/25/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Microembolic signals (MES) can be detected using transcranial Doppler (TCD) ultrasound in several clinical scenarios, including acute ischemic stroke (AIS). This narrative review aims to provide insights into their role in AIS patient management and outcomes. METHODS The present narrative review consolidates current observational and randomized evidence on the prevalence and clinical relevance of MES in different AIS subtypes and settings. RESULTS MES prevalence is higher in AIS patients with large artery atherosclerosis, indicating unstable or vulnerable plaques, and lower in those with small vessel disease. Detecting MES can significantly aid in managing AIS patients, particularly when the cause is unclear, as MES detected in different cerebral arteries can indicate conditions like covert cardioembolism, aortic arch atherosclerosis, or coagulation disorders, including cancer-related stroke. MES are associated with higher risk of stroke recurrence, independently of the underlying stroke mechanism. The detection of MES during and after acute systemic or endovascular reperfusion procedures in large-vessel occlusion patients appears to be predictive of adverse clinical outcomes and recurrent stroke. Finally, a reduction in MES detection may serve as surrogate marker and intermediate endpoint evaluating secondary stroke prevention treatments in the settings of randomized-controlled clinical trials. CONCLUSION MES detection on TCD in AIS remains a useful diagnostic tool as it helps the clinicians to approach the stroke underlying mechanism by detecting and quantifying ongoing cerebral embolization and localizing an embolic source in real time. In addition, it allows monitoring and treatment individualization in stroke patients, while further determining recurrent stroke risk.
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Affiliation(s)
- Eleni Bakola
- Second Department of Neurology, School of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Lina Palaiodimou
- Second Department of Neurology, School of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | | | | | - Theodoros Karapanayiotides
- Second Department of Neurology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christos Moschovos
- Second Department of Neurology, School of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Vijay K Sharma
- Division of Neurology, YLL School of Medicine, National University of Singapore, National University Hospital, Singapore, Singapore
| | - Mark N Rubin
- Edward Hines, Jr. Veterans Affairs Medical Center, Hines, Illinois, USA
| | - João Sargento Freitas
- Department of Neurology, Universidade de Coimbra Faculdade de Medicina, Coimbra, Portugal
| | - Claudio Baracchini
- Stroke Center and Neurosonology Laboratory, Department of Neuroscience, Padua University Hospital, Padova, Italy
| | | | - Andrei V Alexandrov
- Department of Neurology, Banner University Hospital, University of Arizona College of Medicine, Phoenix, USA
| | - Tsivgoulis Georgios
- Second Department of Neurology, School of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Ryan D, Bou Dargham T, Ikramuddin S, Shekhar S, Sengupta S, Feng W. Epidemiology, Pathophysiology, and Management of Cancer-Associated Ischemic Stroke. Cancers (Basel) 2024; 16:4016. [PMID: 39682202 DOI: 10.3390/cancers16234016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Cancer and stroke are leading causes of global disability and mortality. With improvements in cancer-associated mortality and advancements in treatment of active malignancy, it is more common to encounter patients with ischemic stroke and active malignancy. Evidence suggests that cancer-associated ischemic stroke is a unique subtype of stroke; however, there is limited guidance when considering diagnostic workup, secondary prevention, rehabilitation, and future directions within this population. In this narrative review, we aim to describe the epidemiology, pathophysiological mechanisms, management, and future directions regarding understanding of cancer-associated ischemic stroke.
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Affiliation(s)
- Dylan Ryan
- Department of Neurology, Duke University School of Medicine, Durham, NC 27704, USA
| | - Tarek Bou Dargham
- Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA
| | - Salman Ikramuddin
- Department of Neurology, University of Texas Health Sciences Houston, Houston, TX 77030, USA
| | - Shashank Shekhar
- Department of Neurology, Duke University School of Medicine, Durham, NC 27704, USA
| | - Soma Sengupta
- Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Wuwei Feng
- Department of Neurology, Duke University School of Medicine, Durham, NC 27704, USA
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Essibayi MA, Azzam AY, Sener U, Altschul D, Atik M, Keser Z. Direct Oral Anticoagulants vs. Heparin for Cancer-Related Stroke: Augmented Meta-Analysis. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.11.14.24317340. [PMID: 39677488 PMCID: PMC11643248 DOI: 10.1101/2024.11.14.24317340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
Background Ischemic stroke is common among patients with systemic malignancy, associated with increased risk of neurological deterioration and mortality compared to the general population. Optimal approach to secondary stroke prevention in cancer patients is unclear. In this meta-analysis, we evaluated available data on the use of direct oral anticoagulants (DOACs) and heparin products for stroke prevention in this population. Methods Using the Nested Knowledge AutoLit software, we performed PubMed search in September 2023 for articles reporting the use of antithrombotics for cancer-associated stroke. We conducted systematic review and meta-analysis. We also used a novel computational augmentation method to amplify the sample size to predict the effect before and after sample size augmentation and predict the results of further trials. Results Among 253 potential studies screened, 7 were eligible for inclusion. 439 patients were treated with DOACs and 3968 with heparin products. Among patients treated with heparin, intracerebral hemorrhage (8.8 % vs 1.6, p=.02), overall hemorrhagic complications (17.9% vs 3.5%, p<.001), and mortality [28.1% vs 23.5%, p<.001] were respectively significantly higher than those reported among patients who received DOAC for cancer-associated ischemic stroke. No significant difference was observed in the rates of recurrent deep venous thrombosis, clinically significant hemorrhage, and clinical outcomes between the treatment groups. Similar results were shown with augmented meta-analysis. Conclusions This meta-analysis shows DOACs may have efficacy and safety profile similar to heparin products for recurrent stroke prevention in patients with cancer. Given the small number of studies and limited data, findings should be interpreted with caution.
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Affiliation(s)
- Muhammed Amir Essibayi
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
- Department of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ahmed Y. Azzam
- Department of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ugur Sener
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - David Altschul
- Department of Neurosurgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Merve Atik
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
| | - Zafer Keser
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
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4
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Sato T, Ogihara Y, Yamashita Y, Morimoto T, Chatani R, Kaneda K, Nishimoto Y, Ikeda N, Kobayashi Y, Ikeda S, Kim K, Inoko M, Takase T, Tsuji S, Oi M, Takada T, Otsui K, Sakamoto J, Inoue T, Usami S, Chen PM, Togi K, Koitabashi N, Hiramori S, Doi K, Mabuchi H, Tsuyuki Y, Murata K, Takabayashi K, Nakai H, Sueta D, Shioyama W, Dohke T, Nishikawa R, Kimura T, Dohi K. Incidence and risk factors of ischemic stroke in patients with cancer-associated venous thromboembolism: from the Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2. Res Pract Thromb Haemost 2024; 8:102617. [PMID: 39634322 PMCID: PMC11616038 DOI: 10.1016/j.rpth.2024.102617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/26/2024] [Accepted: 10/22/2024] [Indexed: 12/07/2024] Open
Abstract
Background Ischemic stroke is a serious complication in patients with cancer-associated venous thromboembolism (CAVTE), although data remain scarce in the direct oral anticoagulant era. Objectives This study aimed to investigate the incidence and identify predictive risk factors of ischemic stroke in patients with CAVTE. Methods From the Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2 enrolling 5197 venous thromboembolism (VTE) patients across 31 centers in Japan between January 2015 and August 2020, we selected 1507 patients with active cancer. We calculated the cumulative incidence function of ischemic stroke accounting for the competing risk of death and investigated risk factors for ischemic stroke in a subdistribution hazard model of multivariable analysis. Results During a median follow-up period of 1020 days, 71 patients (4.7%) developed ischemic stroke, and the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years. Independent risk factors of ischemic stroke included pancreatic cancer (hazard ratio [HR], 4.24; 95% CI, 2.13-8.43), ovarian cancer (HR, 2.82; 95% CI, 1.31-6.08), lung cancer (HR, 2.35; 95% CI, 1.20-4.57), dyslipidemia (HR, 1.76; 95% CI, 1.01-3.09), metastasis (HR, 1.70; 95% CI, 1.02-2.82), higher D-dimer at VTE diagnosis (HR, 1.09; 95% CI, 1.04-1.14), and younger age (HR, 0.84; 95% CI, 0.71-0.999). Conclusion In this large VTE registry in the direct oral anticoagulant era, the cumulative incidence of ischemic stroke was 4.0% at 1 year and 4.7% at 3 years in patients with CAVTE, and several independent risk factors of ischemic stroke were identified, including pancreatic cancer, ovarian cancer, lung cancer, dyslipidemia, metastasis, higher D-dimer at VTE diagnosis, and younger age.
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Affiliation(s)
- Toru Sato
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yoshito Ogihara
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yugo Yamashita
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takeshi Morimoto
- Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Ryuki Chatani
- Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan
| | - Kazuhisa Kaneda
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuji Nishimoto
- Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
| | - Nobutaka Ikeda
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Yohei Kobayashi
- Department of Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan
| | - Satoshi Ikeda
- Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kitae Kim
- Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Moriaki Inoko
- Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Toru Takase
- Department of Cardiology, Kinki University Hospital, Osaka, Japan
| | - Shuhei Tsuji
- Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Maki Oi
- Department of Cardiology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Takuma Takada
- Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Kazunori Otsui
- Department of General Internal Medicine, Kobe University Hospital, Kobe, Japan
| | - Jiro Sakamoto
- Department of Cardiology, Tenri Hospital, Tenri, Japan
| | - Takeshi Inoue
- Department of Cardiology, Shiga General Hospital, Moriyama, Japan
| | - Shunsuke Usami
- Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan
| | - Po-Min Chen
- Department of Cardiology, Osaka Saiseikai Noe Hospital, Osaka, Japan
| | - Kiyonori Togi
- Division of Cardiology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan
| | - Norimichi Koitabashi
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Seiichi Hiramori
- Department of Cardiology, Kokura Memorial Hospital, Kokura, Japan
| | - Kosuke Doi
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Hiroshi Mabuchi
- Department of Cardiology, Koto Memorial Hospital, Higashiomi, Japan
| | - Yoshiaki Tsuyuki
- Division of Cardiology, Shimada General Medical Center, Shimada, Japan
| | - Koichiro Murata
- Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka, Japan
| | | | - Hisato Nakai
- Department of Cardiovascular Medicine, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Japan
| | - Daisuke Sueta
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Wataru Shioyama
- Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Tomohiro Dohke
- Division of Cardiology, Kohka Public Hospital, Koka, Japan
| | - Ryusuke Nishikawa
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takeshi Kimura
- Department of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan
| | - Kaoru Dohi
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Contemporary Management and Outcomes in Patients With Venous Thromboembolism Registry-2 Investigators
- Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
- Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan
- Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
- Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
- Department of Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan
- Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
- Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
- Department of Cardiology, Kinki University Hospital, Osaka, Japan
- Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
- Department of Cardiology, Japanese Red Cross Otsu Hospital, Otsu, Japan
- Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan
- Department of General Internal Medicine, Kobe University Hospital, Kobe, Japan
- Department of Cardiology, Tenri Hospital, Tenri, Japan
- Department of Cardiology, Shiga General Hospital, Moriyama, Japan
- Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan
- Department of Cardiology, Osaka Saiseikai Noe Hospital, Osaka, Japan
- Division of Cardiology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
- Department of Cardiology, Kokura Memorial Hospital, Kokura, Japan
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
- Department of Cardiology, Koto Memorial Hospital, Higashiomi, Japan
- Division of Cardiology, Shimada General Medical Center, Shimada, Japan
- Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka, Japan
- Department of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan
- Department of Cardiovascular Medicine, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Japan
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
- Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
- Division of Cardiology, Kohka Public Hospital, Koka, Japan
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Toi S, Higuchi E, Hosoya M, Arai S, Ishizuka K, Mizuno T, Hoshino T, Tsutsumi Y, Kitagawa K. Association of Transcranial Doppler Microembolic Signal With Short-Term Mortality in Acute Ischemic Stroke and Active Cancer. J Am Heart Assoc 2024; 13:e033634. [PMID: 39082410 DOI: 10.1161/jaha.123.033634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/20/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND This study aimed to clarify the characteristics and survival prediction value of transcranial Doppler microembolic signals (MES) in patients with acute cerebral infarction and active cancer. METHODS AND RESULTS Between 2017 and 2022, 1089 cases of acute cerebral infarction were recorded within 7 days of disease onset. Among them, transcranial Doppler was successful in 33 patients who had active cancer, and these data were analyzed in this study. The primary outcomes were stroke recurrence and mortality at 3 months. The study population had the following characteristics [median (interquartile range)]: age, 70 years (63-78); body mass index, 21.6 (20-24), National Institutes of Health Stroke Scale 3 (1-6), and modified Rankin Scale score at discharge 1 (1-4). The most common cancer types were lung (24%), pancreatic (24%), and intestinal (18%). MES was present in 16 of 33 patients (48.5%). The presence and number of MES were significantly associated with the levels of D-dimer (P <0.001) and C-reactive protein (P=0.012). Moreover, the presence of MES was associated with multiple ischemic lesions and the 3-territory sign on magnetic resonance imaging. Of the 33 patients, 9 died at 3 months, and 1 had stroke recurrence. On Cox multivariate analysis, using the MES-negative group as a reference, the presence of MES was significantly associated with all-cause death (adjusted hazard ratio, 12.19 [95% CI, 1.45-216.85]; P=0.020). CONCLUSIONS In patients with acute ischemic stroke and active cancer, the presence of MES was associated with D-dimer and C-reactive protein levels and multiple and 3-territory ischemic lesions, and was predictive of short-term survival.
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Affiliation(s)
- Sono Toi
- Department of Medicine Tokyo Women's Medical University Adachi Medical Center Tokyo Japan
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Eiko Higuchi
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Megumi Hosoya
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Satoko Arai
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Kentaro Ishizuka
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Takafumi Mizuno
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Takao Hoshino
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
| | - Yukiko Tsutsumi
- Department of Neurology Tokyo Women's Medical University Tokyo Japan
- International St Luke hospital Tokyo Japan
| | - Kazuo Kitagawa
- Department of Medicine Tokyo Women's Medical University Adachi Medical Center Tokyo Japan
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Chung JW, Hwang J, Kim HJ, Seo WK, Ahn MJ, Saver JL, Bang OY. Edoxaban for the treatment of hypercoagulability and cerebral thromboembolism associated with cancer: A randomized clinical trial of biomarker targets. Int J Stroke 2024; 19:645-653. [PMID: 38429253 DOI: 10.1177/17474930241239266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2024]
Abstract
BACKGROUND This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). METHODS In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. RESULTS Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 μg/mL vs 16.9 ± 16.9 μg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. CONCLUSION Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).
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Affiliation(s)
- Jong-Won Chung
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jaechun Hwang
- Department of Neurology, School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea
| | - Hyung Jun Kim
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Woo-Keun Seo
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Myung-Ju Ahn
- Division of Hematology/Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Jeffrey L Saver
- Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Oh Young Bang
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
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Ntaios G, Baumgartner H, Doehner W, Donal E, Edvardsen T, Healey JS, Iung B, Kamel H, Kasner SE, Korompoki E, Navi BB, Pristipino C, Saba L, Schnabel RB, Svennberg E, Lip GYH. Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC. Eur Heart J 2024; 45:1701-1715. [PMID: 38685132 PMCID: PMC11107123 DOI: 10.1093/eurheartj/ehae150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Abstract
One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.
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Affiliation(s)
- George Ntaios
- Department of Internal Medicine, School of Health Sciences, University of Thessaly, Larissa University Hospital, Larissa 41132, Greece
| | - Helmut Baumgartner
- Department of Cardiology III: Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Germany
| | - Wolfram Doehner
- Department of Cardiology (Campus Virchow), Center of Stroke Research Berlin, German Centre for Cardiovascular Research (DZHK) partner site Berlin, Berlin Institute of Health-Center for Regenerative Therapies, Deutsches Herzzentrum der Charité, Charité, Berlin, Germany
| | - Erwan Donal
- Service de Cardiologie et CIC-IT 1414, CHU Rennes, Rennes, France
| | - Thor Edvardsen
- Department of Cardiology, Faculty of Medicine, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway
| | - Jeff S Healey
- Cardiology Division, McMaster University, Hamilton, Canada
| | - Bernard Iung
- Bichat Hospital, APHP and Université Paris-Cité, INSERM LVTS U1148, Paris, France
| | - Hooman Kamel
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medicine, New York, NY, USA
| | - Scott E Kasner
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Eleni Korompoki
- Department of Clinical Therapeutics, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Babak B Navi
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medicine, New York, NY, USA
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Christian Pristipino
- Interventional and Intensive Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1, Rome, Italy
| | - Luca Saba
- Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari—Polo di Monserrato, Cagliari, Italy
| | - Renate B Schnabel
- Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Germany
| | - Emma Svennberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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8
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Zhao B, Jia W, Yuan Y, Li Z. Clinical analysis of twenty-one cases of acute ischemic stroke related to Trousseau syndrome. Neurol Sci 2024; 45:1537-1547. [PMID: 37957481 DOI: 10.1007/s10072-023-07180-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/01/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Trousseau syndrome (TS) is relatively rare and easily overlooked by clinicians, causing misdiagnosis and affecting subsequent treatment. OBJECTIVE In this study, clinical features, laboratory examination, imaging features, treatment, and prognosis of patients with TS were discussed. METHODS AND MATERIAL From February 2018 to April 2022, cases of 21 patients with malignant tumors complicated by acute ischemic stroke (AIS) were admitted to the Neurology Department of the hospital, and were retrospectively analyzed and discussed based on the literature. RESULTS Twenty-one cases were included in the study. Of these, 95.23% (20/21) developed AIS 6-21 months after the onset of malignant tumors, 9.52% (2/21) had ischemic stroke as the first symptom, 4.76% (1/21) had recurrent ischemic stroke, and 14.29% (3/21) subsequently experienced venous and arterial thrombosis events; 80.95% (17/21) were pathologically confirmed to have adenocarcinoma; and 90.47% (19/21) of infarction cases involved multiple blood vessel feeding sites. MRI showed multiregional, multifocal patchy infarcts. D-dimer concentration was higher than normal in all patients. In addition, 61.90% (13/21) of the patients had poor outcomes according to mRS. CONCLUSION TS is a rare clinical type. It is often associated with adenocarcinoma, and the treatment is different from that of conventional cerebral infarction and the prognosis is very poor. In clinical practice, for AIS of unknown cause, if MRI shows multiple small lesions accompanied by a significant increase in D-dimer, routine screening for latent malignant tumors is recommended.
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Affiliation(s)
- Bingqing Zhao
- Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, No. 24, Shijingshan Road, Beijing, 100043, China.
| | - Weihua Jia
- Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, No. 24, Shijingshan Road, Beijing, 100043, China
| | - Ye Yuan
- Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, No. 24, Shijingshan Road, Beijing, 100043, China
| | - Zheng Li
- Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, No. 24, Shijingshan Road, Beijing, 100043, China
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9
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Cheong MA, Leader A. Cancer and arterial thrombosis: therapeutic options. Res Pract Thromb Haemost 2024; 8:102393. [PMID: 38660456 PMCID: PMC11039399 DOI: 10.1016/j.rpth.2024.102393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/21/2024] [Indexed: 04/26/2024] Open
Abstract
A State of the Art lecture titled "Cancer and Arterial Thrombosis: Therapeutic Options" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. This State of the Art review delves into the complex relationship between cancer and arterial thromboembolism (ATE), encompassing acute coronary syndrome, ischemic strokes, and peripheral arterial disease. The burden of cancer-associated ATE is not well defined, but studies indicate elevated risks, particularly in the 6 months after a cancer diagnosis. Incidence varies among cancer subtypes, with lung cancer displaying the highest rates. Additionally, the pathophysiology of cancer-associated ATE involves a multifaceted interplay of cancer-induced hypercoagulopathy, cancer therapy-related thrombosis, and personal risk factor contributors. ATEs are clinically heterogeneous and in the context of cancer have particular mechanistic differences compared with ATE patients without cancer. This requires modifications in approach and tailored management considerations. Specific etiologies contributing to ATE, such as coronary vasospasm and non-bacterial-thrombotic endocarditis, need to be considered. The diagnosis of cancer alone usually does not contraindicate patients to standard guideline-based therapies for the management of ATE, although nuances in treatment may need to be considered in light of the underlying cancer. Atrial fibrillation in cancer patients further complicates the thrombotic landscape. Cancer patients with atrial fibrillation are at a higher risk of ATE, necessitating careful consideration of anticoagulation therapy as clinical benefits and bleeding risks need to be weighed. ATE may also be a presenting sign of underlying malignancy, which requires increased awareness and focused clinical evaluation for cancer in selected cases. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress.
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Affiliation(s)
- May Anne Cheong
- Department of Haematology, Singapore General Hospital, Singapore
| | - Avi Leader
- Department of Medicine, Hematology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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10
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Tisch C, Ernst D, Falke M, Speicher P, Ziaka M. Systemic embolization due to non-bacterial thrombotic endocarditis: An autopsy case report and mini review of the literature. SAGE Open Med Case Rep 2024; 12:2050313X241229576. [PMID: 38292877 PMCID: PMC10826374 DOI: 10.1177/2050313x241229576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/12/2024] [Indexed: 02/01/2024] Open
Abstract
Nonbacterial thrombotic endocarditis is a rare, non-infectious complication associated with hypercoagulable states, such as malignancies and autoimmune diseases. Due to the difficulty distinguishing marantic endocarditis from infective endocarditis, the diagnosis is often delayed or even a postmortem finding. We present the case of a 70-year-old Caucasian female with marantic endocarditis secondary to metastatic duodenal adenocarcinoma. The patient presented with a short history of memory deficits, personality disturbances, and left homonymous hemianopia. Diffusion-weighted magnetic resonance imaging showed multi-territorial bihemispheric cerebral infarctions. Transthoracic echocardiography revealed native mitral valve endocarditis, and serial blood cultures remained negative. Despite antibiotic therapy, the patient's condition continuously deteriorated, and she died within 3 weeks after her initial presentation. Postmortem examination showed a non-bacterial thrombotic endocarditis. Early clinical suspicion and prompt diagnosis are of decisive importance for the survival of the patients.
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Affiliation(s)
- Carmen Tisch
- Department of Internal Medicine, Hospital of Thun, Thun, Switzerland
| | - Daniel Ernst
- Department of Internal Medicine, Hospital of Thun, Thun, Switzerland
| | - Monika Falke
- University of Bern, Institute of Tissue Medicine and Pathology, Bern, Switzerland
| | - Philip Speicher
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Mairi Ziaka
- Department of Internal Medicine, Hospital of Thun, Thun, Switzerland
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11
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Nakamura R, Yamada T, Tanaka S, Sasada A, Shiotsu S, Tani N, Takeda T, Chihara Y, Hirai S, Takemura Y, Yoshimura A, Morimoto K, Iwasaku M, Tokuda S, Kim YH, Takayama K. Comparison of the prognosis of symptomatic cerebral infarction and pulmonary embolism in patients with advanced non-small cell lung cancer. Cancer Med 2023; 12:9097-9105. [PMID: 36707978 PMCID: PMC10166976 DOI: 10.1002/cam4.5647] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 12/03/2022] [Accepted: 01/13/2023] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Lung cancer patients face a high risk of thromboembolism (TE), which is considered to be a poor prognostic factor. However, the impact of symptomatic cerebral infarction (CI) and pulmonary embolism (PE) on the prognosis of advanced non-small cell lung cancer (NSCLC) patients is not fully understood. METHODS We retrospectively identified 46 patients with advanced NSCLC who developed symptomatic CI or PE at five hospitals in Japan between January 2010 and December 2019. Prognosis and biomarker levels after incident CI and PE were investigated. RESULTS Of the 46 patients, 36 developed symptomatic CI, and 10 developed symptomatic PE. The median follow-up duration after incident CI and PE was 18.2 months. Although the proportion of Common Terminology Criteria for Adverse Events grade 4 tended to be higher in patients with PE than in those with CI (30% vs. 11%, p = 0.16), the overall survival (OS) after incident TE tended to be worse in patients with CI than in those with PE (median 2.3 months vs. 9.1 months, log-rank test p = 0.17). Multivariate analysis showed that OS after CI was worse in patients with high D-dimer (DD) levels than in those with low DD levels at the time of incident CI (median 1.3 months vs. 8.3 months, log-rank p < 0.001). CONCLUSIONS This retrospective study demonstrated that the prognosis of patients tended to be poorer after CI than after PE. The DD levels at the time of incident CI might be a promising predictor of clinical outcomes in advanced NSCLC patients who develop CI.
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Affiliation(s)
- Ryota Nakamura
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tadaaki Yamada
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satomi Tanaka
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Aosa Sasada
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Shinsuke Shiotsu
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Nozomi Tani
- Department of Pulmonary Medicine, Japan Community Health care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan
| | - Takayuki Takeda
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Yusuke Chihara
- Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan
| | - Soichi Hirai
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | | | - Akihiro Yoshimura
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kenji Morimoto
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahiro Iwasaku
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shinsaku Tokuda
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Young Hak Kim
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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12
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Xu Y, Wu Z, Xu H. Cancer-related cryptogenic stroke involving the bilateral anterior and the posterior circulations: Diagnostic value of clinical and imaging characteristics. Front Neurol 2022; 13:1032984. [PMID: 36578305 PMCID: PMC9790910 DOI: 10.3389/fneur.2022.1032984] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022] Open
Abstract
Objectives This study analyzed the clinical and imaging characteristics of patients with cancer-related cryptogenic stroke (CCS) involving the bilateral anterior and the posterior circulations (three circulations) and evaluate the diagnostic value of clinical and imaging features for patients with cryptogenic stroke involving three circulations (CST). Methods Of the 12,580 patients with acute ischemic stroke, 148 patients with CST from May 2017 to November 2021 were divided into the cancer group (n = 81) and the non-cancer group (n = 67). Cardiovascular risk factors, diffusion-weighted imaging patterns of cryptogenic stroke, blood routine, coagulation routine, and biochemical routine were compared between the two groups. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine associations between the two groups. Results Compared with the non-cancer group, the cancer group exhibited higher D-dimer levels (P < 0.001), fibrin degradation product (FDP, P < 0.001), international normalized ratio (INR, P = 0.014), neutrophil to lymphocyte ratio (NLR, P < 0.001), platelets to lymphocyte ratio (PLR, P = 0.001), activated partial thromboplastin time (APTT, P = 0.039), more frequent multiple lesions in three circulations (P < 0.001) and lower lymphocytes (P < 0.001), red blood cells (P < 0.001), and thrombin time (TT, P = 0.034). Furthermore, D-dimer [area under the curve (AUC) = 0.915, P < 0.001)], FDP (AUC = 0.923, P < 0.001), INR (AUC = 0.617, P = 0.014), NLR (AUC = 0.700, P < 0.001), PLR (AUC = 0.658, P = 0.001), and multiple lesions in three circulations (AUC = 0.786, P < 0.001) had potential diagnostic value in cryptogenic stroke. When combining these 6 parameters, the predictive power was improved (AUC = 0.949, P < 0.001). Conclusion Cryptogenic stroke involving three circulations with cancer has unique clinical features, and these potential diagnostic indicators could help patients identify CCS earlier.
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Affiliation(s)
- Yifan Xu
- Department of Radiology, Affiliated Hospital 4 of Nantong University, Yancheng, China,Department of Radiology, Yancheng First People's Hospital, Yancheng, China
| | - Zhuang Wu
- Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China,Zhuang Wu
| | - Hang Xu
- Department of Neurology, Jiangsu University Affiliated People's Hospital, Zhenjiang, China,Department of Neurology, Zhenjiang First People's Hospital, Zhenjiang, China,*Correspondence: Hang Xu
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13
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Zedde M, Portaro G, Ferri L, Cavallieri F, Napoli M, Moratti C, Piazza F, Valzania F, Pascarella R. Neurovascular Manifestations of Iron-Deficient Anemia: Narrative Review and Practical Reflections through a Teaching Case. J Clin Med 2022; 11:jcm11206088. [PMID: 36294407 PMCID: PMC9605151 DOI: 10.3390/jcm11206088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/05/2022] [Accepted: 10/13/2022] [Indexed: 11/19/2022] Open
Abstract
Anemia is one of the most frequent diseases worldwide, affecting one-third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra-cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. The presented case concerns a 46-year-old man admitted to the Stroke Unit because of acute ischemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, such as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed, and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet been defined, and each case should be individually addressed in a pragmatic clinical road map.
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Affiliation(s)
- Marialuisa Zedde
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
- Correspondence: or
| | - Giacomo Portaro
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Laura Ferri
- Department of Neuroscience, Imaging and Clinical Sciences, University G. d’Annunzio of Chieti-Pescara, 66100 Chieti, Italy
| | - Francesco Cavallieri
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Manuela Napoli
- Neuroradiology Unit, Radiology Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Claudio Moratti
- Neuroradiology Unit, Radiology Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Fabrizio Piazza
- CAA and AD Translational Research and Biomarkers Laboratory, School of Medicine and Surgery, University of Milano—Bicocca, Via Cadore 48, 20900 Monza, Italy
| | - Franco Valzania
- Neurology Unit, Neuromotor and Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Rosario Pascarella
- Neuroradiology Unit, Radiology Department, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
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14
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Chen YJ, Dong RG, Zhang MM, Sheng C, Guo PF, Sun J. Cancer-related stroke: Exploring personalized therapy strategies. Brain Behav 2022; 12:e2738. [PMID: 35938982 PMCID: PMC9480895 DOI: 10.1002/brb3.2738] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/01/2022] [Accepted: 07/07/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Cancer and ischemic stroke are two common diseases that threaten human health and have become the main causes of death in the world. It is estimated that one-in-ten patients with ischemic stroke have concomitant cancer, and this incidence is expected to increase as improvements in medical technology extends the life expectancy of cancer patients. DISCUSSION Cancer-related stroke (CRS) refers to unexplained ischemic stroke in patients with active cancer that cannot be explained by current stroke mechanisms. Available evidence suggests that CRS accounts for 5-10% of embolic stroke of undetermined source (ESUS). Although the incidence of CRS is gradually increasing, its underlying pathogenesis remains unclear. Also, there is no consensus on acute treatment and secondary prevention of stroke. CONCLUSION In this review, we retrospectively analyzed the incidence, mechanisms of CRS, its potential as a new stroke subtype, options for acute treatment, secondary prevention strategies, and disease progression, with the aim of attempting to explore personalized therapy strategies.
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Affiliation(s)
- Yu-Jie Chen
- Department of Neurological Rehabilitation, Xuzhou Central Hospital, Xuzhou city, P.R. China
| | - Rui-Guo Dong
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou city, P.R. China
| | - Meng-Meng Zhang
- Department of Neurological Rehabilitation, Xuzhou Central Hospital, Xuzhou city, P.R. China
| | - Chao Sheng
- Department of Neurological Rehabilitation, Xuzhou Central Hospital, Xuzhou city, P.R. China
| | - Peng-Fei Guo
- Department of Neurological Rehabilitation, Xuzhou Central Hospital, Xuzhou city, P.R. China
| | - Jie Sun
- Department of Neurological Rehabilitation, Xuzhou Central Hospital, Xuzhou city, P.R. China
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15
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Woock M, Martinez-Majander N, Seiffge DJ, Selvik HA, Nordanstig A, Redfors P, Lindgren E, Sanchez van Kammen M, Rentzos A, Coutinho JM, Doyle K, Naess H, Putaala J, Jood K, Tatlisumak T. Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach. Ther Adv Neurol Disord 2022; 15:17562864221106362. [PMID: 35785404 PMCID: PMC9243376 DOI: 10.1177/17562864221106362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 05/24/2022] [Indexed: 12/03/2022] Open
Abstract
The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.
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Affiliation(s)
- Malin Woock
- Department of Neurology, Sahlgrenska University Hospital, Blå stråket 7, 413 46 Gothenburg, Sweden
| | | | - David J Seiffge
- Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - Annika Nordanstig
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Petra Redfors
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Erik Lindgren
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Mayte Sanchez van Kammen
- Department of Neurology, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Alexandros Rentzos
- Department of Radiology, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Jonathan M Coutinho
- Department of Neurology, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Karen Doyle
- Department of Physiology, Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Galway, Ireland
| | - Halvor Naess
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Jukka Putaala
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
| | - Katarina Jood
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Turgut Tatlisumak
- Department of Clinical Neuroscience, Institute of Neurosciences and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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16
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Wei Y, Tang S, Xie Z, He Y, Zhang Y, Xie Y, Chen S, Liu L, Liu Y, Liang Z. Pulmonary Tuberculosis-Related Ischemic Stroke: A Retrospective Case Control Study. J Inflamm Res 2022; 15:4239-4249. [PMID: 35923909 PMCID: PMC9341260 DOI: 10.2147/jir.s368183] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 07/01/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Yunfei Wei
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Shiting Tang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
| | - Zhouhua Xie
- Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China
| | - Yaoqin He
- Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China
| | - Yunli Zhang
- Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China
| | - Yiju Xie
- Department of Neurology, Wuming hospital of Guangxi Medical University, Nanning, People’s Republic of China
| | - Shijian Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
| | - Liuyu Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
| | - Yayuan Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China
- Correspondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email
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17
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Nakajima S, Kawano H, Yamashiro K, Tanaka R, Kameda T, Kurita N, Hira K, Miyamoto N, Ueno Y, Watanabe M, Hirano T, Fujimoto S, Urabe T, Hattori N. Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke. Front Neurol 2022; 13:868137. [PMID: 35444612 PMCID: PMC9015657 DOI: 10.3389/fneur.2022.868137] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/17/2022] [Indexed: 12/21/2022] Open
Abstract
Background and Objective Hypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke. Methods This retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission. Results Of 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 μg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60–25.70; P < 0.001) and mortality (adjusted OR, 9.38; 95% CI, 3.32–26.44; P < 0.001). Pre-treatment plasma D-dimer levels ≥10 μg/ml were not associated with these outcomes. Patients who received heparin had higher pre-treatment plasma D-dimer levels than those treated with other anticoagulants. Heparin produced a significant reduction in D-dimer levels from pre- to post-treatment without increasing the incidence of hemorrhagic events. Conclusion A high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.
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Affiliation(s)
- Sho Nakajima
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Hiroyuki Kawano
- Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan
| | - Kazuo Yamashiro
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Ryota Tanaka
- Division of Neurology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
| | - Tomoaki Kameda
- Department of Neurology, Shin-Oyama City Hospital, Tochigi, Japan
| | - Naohide Kurita
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Kenichiro Hira
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
| | - Nobukazu Miyamoto
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yuji Ueno
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
| | - Masao Watanabe
- Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Teruyuki Hirano
- Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan
| | - Shigeru Fujimoto
- Division of Neurology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
| | - Takao Urabe
- Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Nobutaka Hattori
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
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18
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Liu Y, Lu L, Cheng X, Qin Q, Wei Y, Wang D, Li H, Li G, Liang H, Li S, Liang Z. The Index of Esophageal Cancer Related Ischemic Stroke: A Retrospective Patient Control Study. Neuropsychiatr Dis Treat 2022; 18:477-485. [PMID: 35264850 PMCID: PMC8900636 DOI: 10.2147/ndt.s355878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 02/18/2022] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke. METHODS We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden's J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors. RESULTS A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051-1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002-1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628-3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index. CONCLUSION It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.
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Affiliation(s)
- Yayuan Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China
| | - Lizhi Lu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China
| | - Xuemin Cheng
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China
| | - Qixiong Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China
| | - Yunfei Wei
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Province, People's Republic of China
| | - Dacheng Wang
- Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, 536000, Guangxi Province, People's Republic of China
| | - Haihua Li
- Department of Neurology, Fusui County People's Hospital, Chongzuo, 532100, Guangxi Province, People's Republic of China
| | - Guohui Li
- Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, 543002, Guangxi Province, People's Republic of China
| | - Hongbin Liang
- Department of Neurology, Cenxi People's Hospital, Cenxi, 543200, Guangxi Province, People's Republic of China
| | - Shengyu Li
- Department of Neurology, The Affiliated Wuming Hospital of Guangxi Medical University, Nanning, 530100, Guangxi Province, People's Republic of China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China
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19
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Kim HJ, Chung JW, Bang OY, Cho YH, Lim YJ, Hwang J, Seo WK, Kim GM, Kim HJ, Ahn MJ. The Role of Factor Xa-Independent Pathway and Anticoagulant Therapies in Cancer-Related Stroke. J Clin Med 2021; 11:jcm11010123. [PMID: 35011864 PMCID: PMC8745325 DOI: 10.3390/jcm11010123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/18/2021] [Accepted: 12/23/2021] [Indexed: 01/11/2023] Open
Abstract
Background: The optimal strategy for stroke prevention in cancer patients is unknown. We compared the underlying mechanisms of coagulopathy and the effects of anticoagulants in patients with active cancer and atrial fibrillation (AF). Methods: We retrospectively enrolled 46 consecutive patients with embolic stroke of unknown source and active cancer (cancer stroke). We consecutively screened patients with cancer patients without stroke (n = 29), AF stroke (n = 52), and healthy subjects (n = 28), which served as controls. Patients with cancer stroke were treated with either enoxaparin (a low-molecular-weight heparin) or a factor Xa inhibitor, and those with AF stroke were treated with factor Xa inhibitors. D-dimer, factor Xa, and circulating cell-free DNA (cfDNA), a marker of neutrophil extracellular traposis, were measured at both before and after anticoagulation. Results: In AF stroke, factor Xa activity and cfDNA and D-dimer levels were decreased by treatment with factor Xa inhibitors. In contrast, in cancer stroke, factor Xa activity was decreased, D-dimer levels were unchanged, and cfDNA levels were increased by treatment with factor Xa inhibitors. In cancer stroke patients treated with enoxaparin, D-dimer levels were decreased (p = 0.011) and cfDNA levels were unchanged. Conclusion: The anticoagulation effects of factor Xa inhibitors differed between cancer stroke and AF stroke.
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Affiliation(s)
- Hyung Jun Kim
- Department of Neurology, Seoul Hospital, College of Medicine, Ewha Woman’s University, Seoul 07804, Korea;
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
| | - Jong-Won Chung
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
| | - Oh Young Bang
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Korea;
- Correspondence: ; Tel.: +82-2-3410-3599; Fax: +82-2-3410-1430
| | - Yeon Hee Cho
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Korea;
| | - Yun Jeong Lim
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Korea;
| | - Jaechun Hwang
- Department of Neurology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu 41404, Korea;
| | - Woo-Keun Seo
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
| | - Gyeong-Moon Kim
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea; (J.-W.C.); (Y.J.L.); (W.-K.S.); (G.-M.K.)
| | - Hee-Jin Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea;
| | - Myung-Ju Ahn
- Department of Hemato-Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea;
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20
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Nam KW, Kwon HM, Lee YS. Effects of intracranial atherosclerosis and atrial fibrillation on the prognosis of ischemic stroke with active cancer. PLoS One 2021; 16:e0259627. [PMID: 34739530 PMCID: PMC8570487 DOI: 10.1371/journal.pone.0259627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/25/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND In ischemic stroke patients with active cancer, cryptogenic stroke has worse prognosis than stroke by conventional mechanisms. However, the individual effects of intracranial atherosclerosis (ICAS) or atrial fibrillation (AF) on the prognosis of these patients have not been studied. AIMS Therefore, we aimed to investigate the effects of ICAS and AF on the prognosis of ischemic stroke patients with active cancer. METHODS We included ischemic stroke patients with active cancer between 2010 and 2020. Early neurological deterioration (END) was defined as an increase of ≥ 1 in the motor NIHSS score, or ≥ 2 in the total NIHSS score within 72 hours of admission. Unfavorable outcomes were defined as a score of ≥ 3 on the 3-month modified Rankin Scale. RESULTS In total, 116 ischemic stroke patients with active cancer were evaluated. In multivariable analysis, ICAS was positively associated with END (adjusted odds ratio [aOR] = 4.56, 95% confidence interval [CI]: 1.52-13.70), and this association showed a quantitative relationship according to the degree of stenosis of ICAS (stenosis group: aOR = 4.24, 95% CI: 1.31-13.72; occlusion group, aOR = 5.74, 95% CI: 1.05-31.30). ICAS was also closely related to unfavorable outcomes (aOR = 6.33, 95% CI: 1.15-34.79). In contrast, AF showed no significant association with END or unfavorable outcomes. Our data showed that patients with ICAS had larger and more severe initial stroke lesions, and poorer prognosis than those without. CONCLUSIONS ICAS, but not AF, was closely associated with poor prognosis in ischemic stroke patients with active cancer.
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Affiliation(s)
- Ki-Woong Nam
- Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyung-Min Kwon
- Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong-Seok Lee
- Department of Neurology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
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21
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Navi BB, Sherman CP, Genova R, Mathias R, Lansdale KN, LeMoss NM, Wolfe J, Skakodub A, Kamel H, Tagawa ST, Saxena A, Ocean AJ, Soff GA, DeSancho MT, Iadecola C, Elkind MSV, Peerschke E, Zhang C, DeAngelis LM. Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study. Ann Neurol 2021; 90:159-169. [PMID: 34029423 DOI: 10.1002/ana.26129] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/21/2021] [Accepted: 05/21/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. METHODS We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. RESULTS Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). INTERPRETATION Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.
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Affiliation(s)
- Babak B Navi
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York.,Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Carla P Sherman
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Richard Genova
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Ryna Mathias
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Kelsey N Lansdale
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Natalie M LeMoss
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Julia Wolfe
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Anna Skakodub
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Hooman Kamel
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Scott T Tagawa
- Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Ashish Saxena
- Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Allyson J Ocean
- Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Gerald A Soff
- Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maria T DeSancho
- Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Costantino Iadecola
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Mitchell S V Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
| | - Ellinor Peerschke
- Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Cenai Zhang
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Lisa M DeAngelis
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York
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22
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Jiang J, Shang X, Zhao J, Cao M, Wang J, Li R, Wang Y, Xu J. Score for Predicting Active Cancer in Patients with Ischemic Stroke: A Retrospective Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5585206. [PMID: 34124248 PMCID: PMC8169246 DOI: 10.1155/2021/5585206] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/01/2021] [Accepted: 05/18/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke. METHODS This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system. RESULTS Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.06-0.48, P < 0.01), elevated serum fibrinogen (OR = 1.72, 95% CI: 1.33-2.22, P < 0.01) and D-dimer levels (OR = 1.43, 95% CI: 1.24-1.64, P <0.01), and stroke of undetermined etiology (OR = 22.87, 95% CI: 9.91-52.78, P < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 μg/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77-0.89, P < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke. CONCLUSIONS We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.
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Affiliation(s)
- Jiwei Jiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xiuli Shang
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Jinming Zhao
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, China
| | - Meihui Cao
- Department of Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, China
| | - Jirui Wang
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Runzhi Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yanli Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jun Xu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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23
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Navi BB, Kasner SE, Elkind MSV, Cushman M, Bang OY, DeAngelis LM. Cancer and Embolic Stroke of Undetermined Source. Stroke 2021; 52:1121-1130. [PMID: 33504187 DOI: 10.1161/strokeaha.120.032002] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.
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Affiliation(s)
- Babak B Navi
- Clinical and Translational Neuroscience Unit, Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, NY (B.B.N.).,Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY (B.B.N., L.M.D.)
| | - Scott E Kasner
- Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia (S.E.K.)
| | - Mitchell S V Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY (M.S.V.E.)
| | - Mary Cushman
- Division of Hematology and Oncology, Department of Medicine, University of Vermont Larner College of Medicine, Burlington (M.C.)
| | - Oh Young Bang
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (O.Y.B.)
| | - Lisa M DeAngelis
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY (B.B.N., L.M.D.)
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24
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Wei Y, Yang Q, Qin Q, Chen Y, Quan X, Wei J, Zhou L, Wang D, Li H, Li G, Li S, Liang Z. Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study. Eur Neurol 2020; 83:41-48. [PMID: 32344398 DOI: 10.1159/000506046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/18/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND The occurrence of ischemic stroke in patients with non-Hodgkin lymphoma (NHL) is not well understood. This study aimed to determine independent risk factors to identity ischemic stroke in non-Hodgkin lymphoma-associated ischemic stroke (NHLAIS) patients. METHODS This retrospective study was conducted on NHLAIS patients and age- and gender-matched NHL patients. We collected clinical data of patients in both groups and used multiple logistic regression analysis to identify independent risk factors for NHLAIS. A receiver operating characteristic (ROC) analysis was used to establish an identification model based on potential risk factors of NHLAIS. RESULTS Sixty-three NHLAIS patients and 63 NHL patients were enrolled. Stage III/IV (58/63, 92.1%) and multiple arterial infarcts (44/63, 69.8%) were common among NHLAIS patients. Notably, NHLAIS patients had higher levels of serum fibrinogen (FIB), D-dimer, and ferritin (SF) and prolonged thromboplastin time and prothrombin time (PT) compared with NHL patients (all p < 0.05). Elevated FIB, D-dimer, and SF and prolonged PT were independent risk factors for NHLAIS. The area under the ROC curve of the identification model of NHLAIS patients was largest compared to that of other risk factors (0.838, 95% confidence interval: 0.759-0.899) (p < 0.05). CONCLUSION This study reveals that elevated serum FIB, D-dimer, and SF and prolonged PT are potential independent risk factors of NHLAIS. The identification model established in this study may help monitor NHL patients who are at high risk of developing NHLAIS.
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Affiliation(s)
- Yunfei Wei
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qingqing Yang
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qixiong Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Ya Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xuemei Quan
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jing Wei
- Department of Neurology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Liyuan Zhou
- Department of Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Dacheng Wang
- Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, China
| | - Haihong Li
- Department of Neurology, Fusui County People's Hospital, Chongzuo, China
| | - Guohui Li
- Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, China
| | - Shengyu Li
- Department of Neurology, Wuming County People's Hospital, Nanning, China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China,
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25
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Quan X, Qin Q, Chen Y, Wei Y, Xie X, Wang D, Li H, Li S, Cheng D, Liang Z. Independent risk factors and the potential predictors of bladder cancer-related ischemic stroke. J Int Med Res 2020; 48:300060520919227. [PMID: 32338169 PMCID: PMC7218468 DOI: 10.1177/0300060520919227] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective To investigate the independent risk factors and potential predictors of bladder cancer-related ischemic stroke (BCRIS). Methods This was a multi-center retrospective study including patients with active bladder cancer and acute ischemic stroke without traditional stroke risk factors (BCRIS group), and sex- and age-matched patients with active bladder cancer alone (control group). Data were collected between January 2006 and December 2018. Uni- and multivariate analyses were performed to identify independent risk factors for BCRIS. The predictive performance of these risk factors was assessed using receiver operating characteristic (ROC) curves. Results Records were retrospectively reviewed from 60 BCRIS patients and 120 bladder cancer controls. Univariate analysis revealed that serum D-dimer and carcinoembryonic antigen (CEA) levels and the platelet and neutrophil counts were significantly higher in BCRIS patients compared with controls. Multivariate analysis identified the three above-mentioned variables as independent risk factors for BCRIS. The product of all three factors gave the largest area under the ROC curve. Conclusions Elevated serum D-dimer and CEA levels and increased platelet count were independent risk factors for BCRIS, and the cut-off value based on the product of the three independent risk factors (≥2,640,745.29) could serve as a potential predictor of BCRIS.
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Affiliation(s)
- Xuemei Quan
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi Province, China
| | - Qixiong Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi Province, China
| | - Ya Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi Province, China
| | - Yunfei Wei
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, Guangxi Province, China
| | - Xianlong Xie
- Intensive Care Unit, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi Province, China
| | - Dacheng Wang
- Department of Neurology, Guangxi Medical University Ninth Affiliated Hospital, Beihai, Guangxi Province, China
| | - Haihua Li
- Department of Neurology, Fusui County People's Hospital, Chongzuo, Guangxi Province, China
| | - Shengyu Li
- Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi Province, China
| | - Daobin Cheng
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi Province, China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, Guangxi Province, China
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Martinez-Majander N, Ntaios G, Liu YY, Ylikotila P, Joensuu H, Saarinen J, Perera KS, Marti-Fabregas J, Chamorro A, Rudilosso S, Prats-Sanchez L, Berkowitz SD, Mundl H, Themeles E, Tiainen M, Demchuk A, Kasner SE, Hart RG, Tatlisumak T. Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial. Eur J Neurol 2020; 27:841-848. [PMID: 32056346 DOI: 10.1111/ene.14172] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 02/08/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND PURPOSE Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).
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Affiliation(s)
- N Martinez-Majander
- Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
| | - G Ntaios
- Department of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Y Y Liu
- Population Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - P Ylikotila
- Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland
| | - H Joensuu
- Department of Oncology, Helsinki University Hospital, Helsinki, Finland
| | - J Saarinen
- Department of Neurology, Vaasa Central Hospital, Vaasa, Finland
| | - K S Perera
- Population Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - J Marti-Fabregas
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute, IIB-Sant Pau, Barcelona, Spain
| | - A Chamorro
- Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, Spain
| | - S Rudilosso
- Department of Neuroscience, Comprehensive Stroke Center, Hospital Clinic, University of Barcelona, Spain
| | - L Prats-Sanchez
- Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute, IIB-Sant Pau, Barcelona, Spain
| | | | - H Mundl
- Bayer Pharma AG, Wuppertal, Germany
| | - E Themeles
- Population Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - M Tiainen
- Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland
| | - A Demchuk
- Calgary Stroke Program, Departments of Clinical Neuroscience and Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - S E Kasner
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
| | - R G Hart
- Population Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - T Tatlisumak
- Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
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27
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Bang OY, Chung JW, Lee MJ, Seo WK, Kim GM, Ahn MJ. Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms. J Stroke 2020; 22:1-10. [PMID: 32027788 PMCID: PMC7005348 DOI: 10.5853/jos.2019.02278] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 12/05/2019] [Indexed: 01/20/2023] Open
Abstract
Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke. Moreover, cancer-related stroke is expected to increase due to advances in cancer treatment and an aging population worldwide. Because cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy), cancer may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus). In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic work ups, D-dimer levels, and infarct patterns. In this review, we summarized the frequency of cancer-related stroke among patients with ischemic stroke, mechanisms of stroke with in cancer patients, and evaluation and treatment of cancer-related stroke. We discussed the possibility of cancer-related stroke as a stroke subtype, and presented the most recent discoveries in the pathomechanisms and treatment of stroke due to cancer-related coagulopathy.
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Affiliation(s)
- Oh Young Bang
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul, Korea
| | - Jong-Won Chung
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Ji Lee
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo-Keun Seo
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyeong-Moon Kim
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Myung-Ju Ahn
- Department of Hemato-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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28
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Ha J, Lee MJ, Kim SJ, Park BY, Park H, Cho S, Chung JW, Seo WK, Kim GM, Bang OY, Chung CS. Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer. J Am Heart Assoc 2019; 8:e013215. [PMID: 31640456 PMCID: PMC6898837 DOI: 10.1161/jaha.119.013215] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer‐related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer‐related stroke. Methods and Results Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [DVT] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower‐extremity DVT and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion‐weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of DVT and microembolic signal on infarct volume and 1‐year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of DVT or microembolic signal than did the noncancer group (62.2% versus 19.8%; P<0.001). Among patients with cancer‐related stroke, DVT was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95% CI, 1.62–24.66; P=0.028). Presence of DVT (hazard ratio, 16.79; 95% CI, 2.05–137.75; P=0.009) and microembolic signal (hazard ratio, 8.16; 95% CI, 1.36–48.85; P=0.022) were independent predictors of poor 1‐year survival. Conclusions Patients with cancer‐associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1‐year survival. The results of this study may enhance our understanding of cancer‐associated stroke and improve risk stratification of patients with this disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov/.Unique identifier: NCT02212496
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Affiliation(s)
- Jongmok Ha
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Mi Ji Lee
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Suk Jae Kim
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Bo-Yong Park
- Department of Electronic Electrical and Computer Engineering Sungkyunkwan University Suwon Republic of Korea.,Center for Neuroscience Imaging Research Institute for Basic Science (IBS) Suwon Republic of Korea
| | - Hyunjin Park
- Center for Neuroscience Imaging Research Institute for Basic Science (IBS) Suwon Republic of Korea.,School of Electronic and Electrical Engineering Suwon Republic of Korea
| | - Soohyun Cho
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Jong-Won Chung
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Woo-Keun Seo
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Gyeong-Moon Kim
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Oh Young Bang
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
| | - Chin-Sang Chung
- Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
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29
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Chen Y, Qin QX, Qin C, Cheng DB, Huang CX, Wei YF, Liang ZJ. Specific Biomarkers of Prostate Cancer-Associated Ischemic Stroke: A Case-Control Study. Med Sci Monit 2019; 25:5536-5542. [PMID: 31383837 PMCID: PMC6679620 DOI: 10.12659/msm.917970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Ischemic stroke in cancer patients is associated with poor prognosis. However, the specific biomarkers of cancer-associated ischemic stroke (CaIS) have not been well defined. Material/Methods A retrospective study was conducted on PCaIS patients. Clinical data and laboratory and imaging findings were collected. Multivariable logistic regression analysis was used to analyze the independent risk factors for PCaIS. A multiple model combining the independent risk factors of PCaIS was developed using the receiver operating characteristic (ROC) and area under the ROC curve (AUC). Results A total of 83 PCaIS patients and 83 prostate cancer (PCa) patients were included. PCaIS patients had higher levels of D-dimer, neutrophil-to-lymphocyte ratio (NLR), and total prostate-specific antigen (T-PSA). In the multivariate analysis, D-dimer [OR=1.001, 95% CI: 1.00,1.00, P=0.002], NLR [OR=1.12, 95% CI: 1.04,1.22, P=0.005], and T-PSA [OR=6.275, 95% CI: 2.57,15.31, P<0.001] were independent risk factors of PCaIS. Additionally, the AUC of the multiple model of PCaIS was 0.815 (95% CI, 0.750–0.869), with sensitivity of 81.71% and specificity of 70.21%. Conclusions Elevated levels of D-dimer and T-PSA and increased NLR are independent risk factors of PCaIS. The multiple model of PCaIS can be a specific biomarker and is a reliable predictor of development of PCaIS.
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Affiliation(s)
- Ya Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Qi-Xiong Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Chao Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Dao-Bin Cheng
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Chun-Xia Huang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Yun-Fei Wei
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Zhi-Jian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
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30
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Hsu JY, Liu AB. Anticoagulants for cancer-associated ischemic stroke. Tzu Chi Med J 2019; 31:144-148. [PMID: 31258288 PMCID: PMC6559024 DOI: 10.4103/tcmj.tcmj_55_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/24/2018] [Accepted: 02/14/2019] [Indexed: 12/21/2022] Open
Abstract
Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism.
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Affiliation(s)
- Jin-Yi Hsu
- Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - An-Bang Liu
- Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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31
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Park H, Lee HW, Yoo J, Lee HS, Nam HS, Kim YD, Heo JH. Body Mass Index and Prognosis in Ischemic Stroke Patients With Type 2 Diabetes Mellitus. Front Neurol 2019; 10:563. [PMID: 31231300 PMCID: PMC6560048 DOI: 10.3389/fneur.2019.00563] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 05/10/2019] [Indexed: 01/10/2023] Open
Abstract
Background: Overweight contributes to type 2 diabetes mellitus (T2DM) development. Although the obesity paradox has been suggested in many vascular diseases, little information is available about stroke patients with T2DM. We investigated whether body mass index (BMI) has a differential impact on the incidence of major adverse cardiovascular events (MACE) in patients with ischemic stroke and T2DM. Methods: This retrospective study used a prospective cohort of patients with acute ischemic stroke and included consecutive patients with T2DM after excluding those with active cancer or who died within 1 month of an index stroke. We investigated the long-term risk of MACE (stroke, myocardial infarction, unstable angina, coronary revascularization procedure, and death) according to BMI. Results: Among the 1,338 patients, MACE occurred in 415 patients (31.1%) during a median follow-up of 3.6 years. Compared to the normal weight group, MACE occurred more frequently in the underweight group [adjusted hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.01–2.38], but less frequently in the overweight group (adjusted HR: 0.87, 95% CI: 0.70–1.08) and obese group (adjusted HR: 0.58, 95% CI: 0.41–0.86) group. In analyses of association between BMI and each component of MACE, stroke and cardiovascular mortality indicated an L- and a U-shaped pattern, respectively. However, fatal or non-fatal stroke showed an inverse pattern, and fatal or non-fatal cardiovascular events showed a reversed J-shaped pattern. Discussions: This study showed the overall presence of the obesity paradox in stroke patients with T2DM. However, obese patients had different risks of cardiovascular events and stroke.
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Affiliation(s)
- Hyungjong Park
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.,Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea
| | - Hyung Woo Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Joonsang Yoo
- Department of Neurology, Keimyung University School of Medicine, Daegu, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyo Suk Nam
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Young Dae Kim
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
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Abstract
Cancer and cancer therapies might be a risk factor for developing Atrial Fibrillation (AF). It remains unclear if one is the cause or consequence of the other, or if they simply coexist. An unpredictable response to anticoagulation can be expected, as a result of the lack of information in oncology patients. The balance between thromboembolic and bleeding risks of AF in these patients is particularly challenging. Little is known about whether embolic and bleeding risk scores used for the general population can be applied in oncologic patients. Cardiology involvement in the management of these patients seems to be associated with favourable AF-related outcomes.
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Affiliation(s)
- Ana Pardo Sanz
- Cardiology Department, Ramón y Cajal Hospital Madrid, Spain
| | - José Luis Zamorano Gómez
- Cardiology Department, Ramón y Cajal Hospital Madrid, Spain.,Cardiology Department, University of Alcalá, University Hospital La Zarzuela Spain
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33
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Jang HS, Choi J, Shin J, Chung JW, Bang OY, Kim GM, Seo WK, Lee J. The Long-Term Effect of Cancer on Incident Stroke: A Nationwide Population-Based Cohort Study in Korea. Front Neurol 2019; 10:52. [PMID: 30804874 PMCID: PMC6370617 DOI: 10.3389/fneur.2019.00052] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 01/15/2019] [Indexed: 12/18/2022] Open
Abstract
Background and Purpose: Despite the recent growing interest in the cancer–stroke association, the long-term effect, and organ-specific association with stroke incidence in subjects with cancer have not been clearly defined. Methods: Data were obtained from the Korean National Health Insurance Service National Sample Cohort database between 2002 and 2015. To investigate the effects of cancer on stroke incidence, subjects were classified into cancer and non-cancer groups based on the period after cancer diagnosis and origin organ of cancer. To minimize the effects of selection bias, we performed a propensity score matching analysis with covariates of demographic data, vascular risk factors, antithrombotics use and statin use. Incident stroke was diagnosed based on operational definition and classified into ischemic stroke and hemorrhagic stroke. Results: Data of 20,707 subjects with cancer and 675,594 without cancer were analyzed for 7 follow-up years. The subjects with cancer had higher risk of any stroke (subdistribution hazard ratio [SHR], 1.13; 95% confidence interval [CI], 1.02–1.26; p = 0.0181) than those without cancer. Similar trend was found for ischemic stroke (SHR, 1.17; 95% CI, 1.05–1.31; p = 0.0054), but not for hemorrhagic stroke. The risk of stroke was increased in subjects with cancer in the digestive organ, respiratory and intrathoracic organ, and “others (such as breast and female and male reproductive organs)” in 3 years; however, the association disappeared thereafter except those with “others” cancer. Chemotherapy increased the risk of ischemic stroke (SHR 1.21; 95% CI, 1.03–1.41). Conclusions: Cancer increases the risk of stroke at 3 years after the diagnosis of cancer, and the effect was maintained for 7 years. The association between cancer and stroke incidence depends on the organ from which the cancer originated and chemotherapy.
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Affiliation(s)
- Hyun-Soon Jang
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Jimi Choi
- Department of Biostatistics, College of Medicine, Korea University, Seoul, South Korea
| | - Jaewon Shin
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Jong-Won Chung
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Oh Young Bang
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Gyeong-Moon Kim
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Woo-Keun Seo
- Department of Neurology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea.,Department of Digital Health, The Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
| | - Juneyoung Lee
- Department of Biostatistics, College of Medicine, Korea University, Seoul, South Korea
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34
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Qin QX, Cheng XM, Lu LZ, Wei YF, Wang DC, Li HH, Li GH, Liang HB, Li SY, Chen L, Liang ZJ. Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke. World J Gastroenterol 2018; 24:4950-4958. [PMID: 30487704 PMCID: PMC6250925 DOI: 10.3748/wjg.v24.i43.4950] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/02/2018] [Accepted: 11/08/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke (CRCIS).
METHODS A retrospective study was conducted on CRCIS patients (colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age- and sex- matched patients with colorectal cancer (CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS.
RESULTS A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen (CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.001-1.003, P < 0.001], CEA levels (OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels (OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022 (95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%.
CONCLUSION Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study.
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Affiliation(s)
- Qi-Xiong Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Xue-Min Cheng
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Li-Zhi Lu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Yun-Fei Wei
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Province, China
| | - Da-Cheng Wang
- Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai 536000, Guangxi Province, China
| | - Hai-Hua Li
- Department of Neurology, Fusui County People’s Hospital, Chongzuo 532100, Guangxi Province, China
| | - Guo-Hui Li
- Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou 543002, Guangxi Province, China
| | - Hong-Bin Liang
- Department of Neurology, Cenxi People’s Hospital, Cenxi 543200, Guangxi Province, China
| | - Sheng-Yu Li
- Department of Neurology, Wuming County People’s Hospital, Nanning 530100, Guangxi Province, China
| | - Li Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Zhi-Jian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
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Murthy SB, Cushman M, Bobrow D, Kamel H, Merkler AE, Elkind MSV, DeAngelis LM, Navi BB. Ability of the Khorana score to predict recurrent thromboembolism in cancer patients with ischemic stroke. J Clin Neurosci 2018; 57:111-115. [PMID: 30145085 PMCID: PMC6191324 DOI: 10.1016/j.jocn.2018.08.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 07/20/2018] [Accepted: 08/12/2018] [Indexed: 12/12/2022]
Abstract
Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell's c-statistic was used to calculate the score's discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24-149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1-2, range 0-5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1-2, and 32% with scores of 3-6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02-1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11-1.90). The score's c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.
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Affiliation(s)
- Santosh B Murthy
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | - Mary Cushman
- Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA
| | - Dylan Bobrow
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hooman Kamel
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | - Alexander E Merkler
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | - Mitchell S V Elkind
- Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Lisa M DeAngelis
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Babak B Navi
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Jung S, Jung C, Hyoung Kim J, Se Choi B, Jung Bae Y, Sunwoo L, Geol Woo H, Young Chang J, Joon Kim B, Han MK, Bae HJ. Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke. Interv Neuroradiol 2018; 24:520-528. [PMID: 29792090 DOI: 10.1177/1591019918776207] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective Embolism due to coagulopathy might be the main pathomechanism underlying cancer-related stroke (CRS). CRS patients with a large artery occlusion could be candidates for endovascular recanalization therapy (ERT), although its procedural and clinical outcomes are not well known. This study aimed to investigate the procedural and clinical outcomes of ERT in CRS patients and the characteristics associated with outcomes compared with those of conventional stroke patients. Methods A registry of consecutive acute ischemic stroke patients who underwent ERT between January 2011 and October 2015 was retrospectively reviewed. CRS patients are described as those who had (a) cryptogenic stroke with advanced or metastatic cancer; (b) no other possible causes of stroke such as cardioembolism (CE) and large artery atherosclerosis (LAA); and (c) elevated D-dimer levels or diffusion-restricted lesions in multiple vascular territories. We compared procedural and clinical outcomes at discharge among CRS, CE, and LAA patients. Results A total of 329 patients were finally enrolled in this study; of these, 19 were CRS patients. The rate of successful recanalization, defined as modified treatment in cerebral infarction grade 2b or 3, was lower in the CRS group than in the LAA and CE groups (63% versus 84% versus 84%, p = .06). CRS subtype was an independent predictor for successful recanalization after ERT in the multivariate analysis (odds ratio, 0.317; 95% confidence interval, 0.116-0.867; p < .001). No significant difference in the rate of good clinical outcomes at discharge was observed among groups. Conclusions Although clinical outcomes at discharge were similar for CE and LAA patients, complete recanalization seemed more difficult to achieve in CRS patients than in conventional stroke patients.
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Affiliation(s)
- Seunguk Jung
- 1 Department of Neurology, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Cheolkyu Jung
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae Hyoung Kim
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Byung Se Choi
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun Jung Bae
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Leonard Sunwoo
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ho Geol Woo
- 2 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jun Young Chang
- 1 Department of Neurology, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Beom Joon Kim
- 3 Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Moon-Ku Han
- 3 Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hee-Joon Bae
- 3 Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea
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Navi BB, Iadecola C. Ischemic stroke in cancer patients: A review of an underappreciated pathology. Ann Neurol 2018; 83:873-883. [PMID: 29633334 PMCID: PMC6021225 DOI: 10.1002/ana.25227] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 04/02/2018] [Accepted: 04/02/2018] [Indexed: 02/06/2023]
Abstract
Currently 1 in 10 patients with ischemic stroke have comorbid cancer, and this frequency is expected to increase with continued advances in cancer therapeutics prolonging median survival. Well known for its association with venous thrombosis, cancer has recently emerged as a significant risk factor for arterial thromboembolism, including stroke; however, the underlying mechanisms are uncertain. In addition, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established. This review summarizes the current evidence on ischemic stroke risk, biomarkers, pathophysiology, treatments, and prognosis in cancer patients, emphasizing knowledge gaps and the potential strategies to address them. Ann Neurol 2018;83:873-883.
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Affiliation(s)
- Babak B Navi
- Department of Neurology
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Costantino Iadecola
- Department of Neurology
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine
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Long H, Qin K, Chen J, Chen Y, Chen L, Zeng J, Liang Z. Biomarkers of gastric cancer-related ischemic stroke and its underlying pathogenesis. Medicine (Baltimore) 2018; 97:e0493. [PMID: 29703010 PMCID: PMC5944483 DOI: 10.1097/md.0000000000010493] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
This study aimed to investigate the biomarkers and underlying pathogenesis of ischemic stroke in patients with gastric cancer (GC).Patients with active gastric cancer who had experienced acute ischemic stroke without conventional vascular risk factors (gastric cancer-related stroke [GCS] group) and visited The First Affiliated Hospital of Guangxi Medical University and First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2016 were retrospectively enrolled. The patients' clinical features and laboratory findings were compared with those of age-, sex-, and disease progression-matched patients with GC without ischemic stroke (GC group) who had been admitted to the same hospital during the same period (GCS:GC ratio = 1:2).Among the 9166 patients diagnosed with GC, 70 had experienced a cerebral infarction and were enrolled in this study. Among them, 53 (75.71%) harbored multiple lesions in multiple vascular territories. Notably, patients in the GCS group exhibited significant increases in the D-dimer and cancer antigen 125 (CA125) levels and platelet-to-neutrophil ratio (PNR), compared to their counterparts in the GC group. A multiple logistic regression analysis identified all 3 factors as independent risk factors for cerebral infarction in patients with GC (D-dimer, odds ratio [OR] = 1.006 per 1 ng/mL increase, 95% confidence interval [CI], 1.004-1.009, P = .000; CA125, OR = 1.016 per 1 U/mL increase, 95% CI, 1.005-1.027, P = .005; PNR, OR = 1.025 per 1 point increase, 95% CI: 1.003-1.048, P = .023).Elevated plasma D-dimer and CA125 levels and an increased PNR might affect the occurrence of GC-related ischemic stroke and could therefore serve as potential biomarkers.
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Affiliation(s)
- Haiyin Long
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province
| | - Kemin Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province
| | - Jiyun Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province
| | - Yicong Chen
- Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Li Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province
| | - Jinsheng Zeng
- Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province
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Sorgun MH, Kuzu M, Ozer IS, Yilmaz V, Ulukan C, Cotur Levent H, Tezcan S, Rzayev S, Rawandi A, Bakırarar B, Isikay CT. Risk Factors, Biomarkers, Etiology, Outcome and Prognosis of Ischemic Stroke in Cancer Patients. Asian Pac J Cancer Prev 2018; 19:649-653. [PMID: 29580034 PMCID: PMC5980836 DOI: 10.22034/apjcp.2018.19.3.649] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2017] [Indexed: 12/15/2022] Open
Abstract
Introduction: Cerebrovascular disease is the second most common complication in individuals with tumours. The aim of this study was to investigate risk factors, biomarkers, etiology and prognosis of ischemic stroke in cancer patients (ISCPs). Methods: The medical records of 619 consecutive patients who were admitted with acute ischemic stroke from January 2012 to November 2014 were retrospectively evaluated. The patients were divided into two groups (group 1, patients with an active cancer prior to the onset of ischemic stroke; group 2, patients without an active cancer history). The demographic data, risk factors, NIHSS scores, thrombocyte count, D-dimer, fibrinogen and C reactive protein (CRP) level at admission, modified Rankin Scale (mRS) scores in the follow-up period and location of lesions on DWI were recorded. The Mann-Whitney U test, chi-squared test and logistic regression was used for analyzing data, p<0.05 being considered statistically significant. Results: A total of 46 (7.4%) ISCPs were included. Hyperlipidemia was significantly lower in the ISCP group (p=0.001). Elevated thrombocyte counts, D-dimer, fibrinogen and CRP levels at admission, acute multiple ischemic lesions, other causes, mortality in hospital and worse outcome were significantly related to ISCP (p<0.05). On logistic regression analysis, follow up mRS>3, acute multiple ischemic lesions located in more than one vascular territory (AMIMCT) and other causes were significantly associated with ISCP (p<0.001). Conclusion: In our study, other causes, AMIMCT and mRS>3 were more common in the ISCP group. We consider that CCS could be more suitable for detecting other causes than TOAST. Biomarkers could be important in the ISCP group.
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Affiliation(s)
- Mine Hayriye Sorgun
- Ankara University School of Medicine, İbni Sina Hospital, Department of Neurology, Samanpazarı, Ankara Turkey.
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Selvik HA, Bjerkreim AT, Thomassen L, Waje-Andreassen U, Naess H, Kvistad CE. When to Screen Ischaemic Stroke Patients for Cancer. Cerebrovasc Dis 2018; 45:42-47. [PMID: 29402826 DOI: 10.1159/000484668] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 10/25/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND PURPOSE Ischemic stroke can be the first manifestation of cancer and it is therefore important to ascertain which stroke patients should be considered for cancer-diagnostic investigations. We aimed to determine the frequency of active cancer in patients with acute ischemic stroke and to compare clinical findings in stroke patients with active cancer to ischemic stroke patients with no history of cancer. Finally, we aimed to develop a predictive and feasible score for clinical use to uncover underlying malignancy. METHODS All ischemic stroke patients admitted to the stroke unit in the Department of Neurology, Haukeland University Hospital were consecutively included in the Norwegian Stroke Research Registry (NORSTROKE). Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Data on cancer diagnoses was obtained from patients' medical records and the Cancer Registry of Norway. Active cancer was defined as cancer diagnosis, metastasis of known cancer, recurrent cancer or receiving cancer treatment, all within 12 months before or after the index stroke. Based on variables independently associated with active cancer, a predictive score was developed using the area under the receiver operating characteristic (AUC-ROC) curves. Bayes' theorem was used to calculate post-test probabilities of active cancer. RESULTS Of the 1,646 ischemic stroke patients included, 82 (5.0%) had active cancer. Increased D-dimer (OR = 1.1, 95% CI: 1.1-1.2, p = <0.001), lower Hb (OR = 0.6, 95% CI: 0.5-0.7, p = <0.001), smoking (OR = 2.2, 95% CI: 1.2-4.3, p = 0.02) and suffering a stroke of undetermined etiology (OR = 1.9, 95% CI: 1.1-3.3, p = 0.03) were factors independently associated with active cancer. These were included in the final predictive score which gave an AUC of 0.73 (95% CI: 0.65-0.81) in patients younger than 75 years of age. Assuming the prevalence of cancer to be 5%, the score shows that if a patient fulfills all 3 score points, the probability of active cancer is 53%. CONCLUSIONS Active cancer was found in 5% of our ischemic stroke patients. We found that a clinical score comprising elevated D-dimer ≥3 mg/L, lower Hb ≤12.0 g/dL and previous or current smoking is feasible for predicting active cancer in ischemic stroke patients.
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Affiliation(s)
- Henriette Aurora Selvik
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Anna Therese Bjerkreim
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Lars Thomassen
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - Ulrike Waje-Andreassen
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
| | - Halvor Naess
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Neurology, Haukeland University Hospital, Bergen, Norway.,Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway
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Parikh NS, Burch JE, Kamel H, DeAngelis LM, Navi BB. Recurrent Thromboembolic Events after Ischemic Stroke in Patients with Primary Brain Tumors. J Stroke Cerebrovasc Dis 2017. [PMID: 28647417 DOI: 10.1016/j.jstrokecerebrovasdis.2017.05.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Stroke mechanisms and the risk of recurrent thromboembolism are incompletely understood in patients with primary brain tumors. We sought to better delineate these important clinical features. METHODS We performed a retrospective cohort study of adults with primary brain tumors diagnosed with magnetic resonance imaging-confirmed acute ischemic stroke at the Memorial Sloan Kettering Cancer Center from 2005 to 2015. Study neurologists collected data on patients' cancer history, stroke risk factors, treatments, and outcomes. Stroke mechanisms were adjudicated by consensus. The primary outcome was recurrent thromboembolism (arterial or venous) and the secondary outcome was recurrent ischemic stroke. Kaplan-Meier statistics were used to calculate cumulative outcome rates, and Cox hazards analysis was used to evaluate the association between potential risk factors and outcomes. RESULTS We identified 83 patients with primary brain tumors and symptomatic acute ischemic stroke. Median survival after index stroke was 2.2 years (interquartile range, .5-7.0). Tumors were mostly gliomas (72%) and meningiomas (13%). Most strokes were from unconventional mechanisms, particularly radiation vasculopathy (36%) and surgical manipulation (18%). Small- or large-vessel disease or cardioembolism caused 13% of strokes, whereas 29% were cryptogenic. Cumulative recurrent thromboembolism rates were 11% at 30 days, 17% at 180 days, and 27% at 365 days, whereas cumulative recurrent stroke rates were 5% at 30 days, 11% at 180 days, and 13% at 365 days. We found no significant predictors of outcomes. CONCLUSION Patients with primary brain tumors generally develop strokes from rare mechanisms, and their risk of recurrent thromboembolism, including stroke, is high.
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Affiliation(s)
- Neal S Parikh
- Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Jaclyn E Burch
- Department of Neurology, Weill Cornell Medicine, New York, New York
| | - Hooman Kamel
- Department of Neurology, Weill Cornell Medicine, New York, New York; Clinical and Translational Neuroscience Unit, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York
| | - Lisa M DeAngelis
- Department of Neurology, Weill Cornell Medicine, New York, New York; Clinical and Translational Neuroscience Unit, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Babak B Navi
- Department of Neurology, Weill Cornell Medicine, New York, New York; Clinical and Translational Neuroscience Unit, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
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Intravenous Thrombolysis in Acute Ischemic Stroke with Active Cancer. BIOMED RESEARCH INTERNATIONAL 2017; 2017:4635829. [PMID: 28660209 PMCID: PMC5474258 DOI: 10.1155/2017/4635829] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 04/18/2017] [Accepted: 05/14/2017] [Indexed: 11/18/2022]
Abstract
Ischemic stroke patients with active cancer are known to have poor clinical outcomes. However, the efficacy and safety of intravenous alteplase (IV t-PA) in this group are still unclear. In this study, we aimed to evaluate whether stroke patients with cancer had poor clinical outcomes after use of IV t-PA. We reviewed ischemic stroke patients with active cancer treated with isolated IV t-PA between April 2010 and March 2015 at three national university hospitals from the registry for ischemic stroke in Korea. The clinical outcomes of early neurological deterioration (END), hemorrhagic transformation, in-hospital mortality, 3-month modified Rankin scale (mRS), the National Institutes of Health Stroke Scale (NIHSS) discharge score, and duration of hospitalization were compared. We enrolled a total of 12 patients, and the cohort showed poor outcomes including 4 (33%) END events, 7 (58%) hemorrhagic transformations, 3 (25%) in-hospital mortality cases, and 7 (58%) poor mRS (3-6) scores. Additionally, the cryptogenic stroke group (n = 6) more frequently had high mRS scores (P = 0.043) as well as tendencies for frequent END events, hemorrhagic transformations, in-hospital mortality cases, and higher discharge NIHSS scores without statistical significance. In conclusion, ischemic stroke patients with active cancer, especially those with a cryptogenic mechanism, showed poor clinical outcomes after use of IV t-PA.
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Suero-Abreu GA, Cheng JZ, Then RK. Multiple recurrent ischaemic strokes in a patient with cancer: is there a role for the initiation of anticoagulation therapy for secondary stroke prevention? BMJ Case Rep 2017; 2017:bcr-2016-218105. [PMID: 28578306 PMCID: PMC5534754 DOI: 10.1136/bcr-2016-218105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
A 52-year-old woman with a medical history of cervical and thyroid cancer, hypertension, dyslipidaemia, uncontrolled diabetes and heavy smoking was diagnosed with a new metastatic cholangiocarcinoma. While undergoing palliative chemotherapy, she developed dysarthria and left-sided weakness. Imaging studies showed multiple bilateral ischaemic strokes. On hospital days 2 and 5, she developed worsening neurological symptoms and imaging studies revealed new areas of ischaemia on respective days. Subsequent workup did not revealed a clear aetiology for the multiple ischaemic events and hypercoagulability studies were only significant for a mildly elevated serum D-dimer level. Although guidelines are unclear, full-dose anticoagulation with low molecular weight heparin was initiated given her high risk of stroke recurrence. She was discharged to acute rehabilitation but, within a month, she experienced complications of her malignant disease progression and a new pulmonary thromboembolism. The patient died soon after being discharged home with hospice care.
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Affiliation(s)
- Giselle Alexandra Suero-Abreu
- Department of Medicine, Rutgers University New Jersey Medical School, Newark, New Jersey, USA.,Department of Neurology, Cooper University Hospital, Camden, New Jersey, USA
| | - Jia Zhen Cheng
- Department of Neurology, Cooper University Hospital, Camden, New Jersey, USA
| | - Ryna Karina Then
- Department of Neurology, Cooper University Hospital, Camden, New Jersey, USA
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Petr O, Burrows AM, Brinjikji W, Brown RD, Lanzino G. Management of patients with an unruptured intracranial aneurysm and a history of malignancy. J Neurosurg Sci 2017; 64:413-419. [PMID: 28565897 DOI: 10.23736/s0390-5616.17.04080-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Management of a patient with an unruptured intracranial aneurysm (UIA) who has a history of malignancy can be challenging due to considerations related to the natural history of the aneurysm and risk of recurrence or progression of malignancy. The current study presents our experience with both conservative management and interventional treatment of patients with UIAs and a remote or recent history of cancer. METHODS Consecutive patients with a history of malignancy and UIA were classified into the following groups: Group I (diagnoses of both UIA and cancer within 3 years) and Group II (known cancer with new UIA diagnosed ≥3 years after cancer). Patient demographics, clinical characteristics, aneurysm/treatment characteristics, and outcomes were collected prospectively. We studied the following outcomes: perioperative and mid-/long-term complications, aneurysm rupture, retreatment/recurrence rates, long-term neurological outcome, and possible impact of cancer history on decision-making for treatment. RESULTS A total of 122 patients were included in this study (55 in Group I and 67 in Group II). Patients in Group I underwent aneurysm treatment significantly less often than those in Group II (20.0% versus 46.3%, P=0.002). There was no difference in neurological morbidity rates between the two groups after a mean follow-up of 22.3 months (3.6% versus 3.0%, P=0.29). Overall, untreated patients experienced an annualized rupture rate of 1.6% (95% CI=0.0%-3.4%, 3/187.6 ruptures/person years). CONCLUSIONS Patients with an UIA and a history of cancer should be considered for management with either conservative management or invasive techniques. The optimal UIA management is defined on a case-by-case basis carefully comparing the prognosis of the patient's malignancy with the natural history of the aneurysm and the risk of interventional treatment.
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Affiliation(s)
- Ondra Petr
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.,Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria
| | | | | | - Robert D Brown
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Giuseppe Lanzino
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA - .,Department of Radiology, Mayo Clinic, Rochester, MN, USA
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Jiang H, Qin C, Cheng D, Lu Q, Huang G, Wang D, Yang H, Liang Z. Potential Pathogenesis and Biomarkers of Kidney Cancer-Related Stroke. Med Sci Monit 2017; 23:2292-2298. [PMID: 28505148 PMCID: PMC5441415 DOI: 10.12659/msm.904710] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Stroke risk and stroke recurrence are increased in cancer patients, but the pathogenesis and biomarkers of kidney cancer-related stroke (KCS) are generally unclear. The aim of the present research was to investigate the pathogenesis and plasma biomarkers of kidney cancer-related stroke. MATERIAL AND METHODS A retrospective review was conducted on acute stroke patients with kidney cancer (KC) who were admitted to the hospital between January 2006 and December 2015. A total of 106 patients with KCS (active KC patients with acute stroke but without conventional vascular risks) were identified. In addition, 106 age- and sex-matched patients with KC alone were recruited. RESULTS KCS patients had higher plasma D-dimer, cancer antigen (CA) 125, and CEA levels and greater proteinuria levels than did KC patients. Multiple logistic regression analysis showed that the risk of stroke in patients with KC increased independently by 0.8% (odds ratio [OR] 1.008; 95% confidence interval [CI] 1.002, 1.013; p=0.004) with a 1 ng/mL increase in D-dimer levels, by 1.2% (OR 1.012; 95% CI 1.007, 1.018; p=0.000) with a 1 U/mL increase in CA125, by 2.5% (OR 1.025; 95% CI 1.012, 1.038; p=0.000) with a 1 U/mL increase in CEA by 1.4% (OR 1.014; 95% CI 1.005, 1.024; p=0.004) with a 1 mg increase in urine protein in 24 hours. CONCLUSIONS Elevated plasma D-dimer, CA125 and CEA levels, and increased urine protein levels might lead to hypercoagulability and then KCS; however, they may also be biomarkers of KCS.
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Affiliation(s)
- Haihong Jiang
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Chao Qin
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Daobin Cheng
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Qiuhong Lu
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Gelun Huang
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Dacheng Wang
- Department of Neurology, Ninth Affiliated Hospital of Guangxi Medical University, Beihai, Guangxi, China (mainland)
| | - Hong Yang
- Department of Neurology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China (mainland)
| | - Zhijian Liang
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland)
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Bang OY. Advances in biomarker for stroke patients: from marker to regulator. PRECISION AND FUTURE MEDICINE 2017. [DOI: 10.23838/pfm.2017.00052] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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Nam KW, Kim CK, Kim TJ, An SJ, Oh K, Mo H, Kang MK, Han MK, Demchuk AM, Ko SB, Yoon BW. Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke. PLoS One 2017; 12:e0172793. [PMID: 28282388 PMCID: PMC5345775 DOI: 10.1371/journal.pone.0172793] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 02/09/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Stroke in cancer patients is not rare but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. AIM In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. METHODS We included 210 ischemic stroke patients with active cancer. The 30-day mortality data were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. RESULTS Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS scores, D-dimer levels, and CRP levels as well as frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. The initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independent of D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease in D-dimer levels, despite treatment, while the survivor group showed the opposite response. CONCLUSIONS D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.
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Affiliation(s)
- Ki-Woong Nam
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Chi Kyung Kim
- Department of Neurology, Korea University Guro Hospital and Korea University College of Medicine, Seoul, Korea
- Calgary Stroke Program, Department of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
| | - Tae Jung Kim
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Sang Joon An
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Kyungmi Oh
- Department of Neurology, Korea University Guro Hospital and Korea University College of Medicine, Seoul, Korea
| | - Heejung Mo
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Min Kyoung Kang
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Moon-Ku Han
- Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Andrew M. Demchuk
- Calgary Stroke Program, Department of Clinical Neuroscience and Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
| | - Sang-Bae Ko
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
| | - Byung-Woo Yoon
- Department of Neurology, Seoul National University Hospital, Seoul, Korea
- * E-mail:
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Lee MJ, Chung JW, Ahn MJ, Kim S, Seok JM, Jang HM, Kim GM, Chung CS, Lee KH, Bang OY. Hypercoagulability and Mortality of Patients with Stroke and Active Cancer: The OASIS-CANCER Study. J Stroke 2016; 19:77-87. [PMID: 28030894 PMCID: PMC5307941 DOI: 10.5853/jos.2016.00570] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/25/2016] [Accepted: 10/04/2016] [Indexed: 12/28/2022] Open
Abstract
Background and Purpose Patients with active cancer are at an increased risk for stroke. Hypercoagulability plays an important role in cancer-related stroke. We aimed to test whether 1) hypercoagulability is a predictor of survival, and 2) correction of the hypercoagulable state leads to better survival in patients with stroke and active cancer. Methods We recruited consecutive patients with acute ischemic stroke and active systemic cancer between January 2006 and July 2015. Hypercoagulability was assessed using plasma D-dimer levels before and after 7 days of anticoagulation treatment. The study outcomes included overall and 1-year survival. Plasma D-dimer levels before and after treatment were tested in univariate and multivariate Cox regression models. We controlled for systemic metastasis, stroke mechanism, age, stroke severity, primary cancer type, histology, and atrial fibrillation using the forward stepwise method. Results A total of 268 patients were included in the analysis. Patients with high (3rd–4th quartiles) pre-treatment plasma D-dimer levels showed decreased overall and 1-year survival (adjusted HR, 2.19 [95% CI, 1.46–3.31] and 2.70 [1.68–4.35], respectively). After anticoagulation treatment, post-treatment D-dimer level was significantly reduced and independently associated with poor 1-year survival (adjusted HR, 1.03 [95% CI, 1.01–1.05] per 1 μg/mL increase, P=0.015). The successful correction of hypercoagulability was a protective factor for 1-year survival (adjusted HR 0.26 [CI 0.10–0.68], P=0.006). Conclusions Hypercoagulability is associated with poor survival after stroke in patients with active cancer. Effective correction of hypercoagulability may play a protective role for survival in these patients.
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Affiliation(s)
- Mi Ji Lee
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong-Won Chung
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Myung-Ju Ahn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seonwoo Kim
- Biostatistics Team, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea
| | - Jin Myoung Seok
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hye Min Jang
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyeong-Moon Kim
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chin-Sang Chung
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Ho Lee
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Oh Young Bang
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Xie X, Chen L, Zeng J, Qin C, Cheng D, Wei X, Liang Z. Clinical features and biological markers of lung cancer-associated stroke. J Int Med Res 2016; 44:1483-1491. [PMID: 28322105 PMCID: PMC5536770 DOI: 10.1177/0300060516666398] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective To identify the unique clinical features and biological markers of lung cancer-associated stroke. Methods We recruited 102 patients with lung cancer plus stroke, 102 with lung cancer, and 102 with stroke. Detailed information was analysed and compared among groups. Results The groups were age-matched. Patients with lung cancer plus stroke showed multiple lesions involving multiple cerebral artery territories on magnetic resonance imaging, compared with stroke-alone patients. These patients also had a poorer modified Rankin Scale score at 30 days, and high mortality (18.6%). Patients with lung cancer plus stroke had a higher incidence of metastasis, and higher blood levels of D-dimer, CA125 and CA199 compared with patients with lung cancer alone. Multivariate logistic regression analysis showed that levels of D-dimer, CA125 and CA199 were independently related to lung cancer-associated stroke. Conclusion Elevated plasma D-dimer, CA125 and CA199 may be independent risk factors for and biomarkers of lung cancer-associated stroke.
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Affiliation(s)
- Xingrui Xie
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Li Chen
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jinsheng Zeng
- 2 Department of Neurology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chao Qin
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Daobin Cheng
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xinxian Wei
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhijian Liang
- 1 Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Finelli PF, Nouh A. Three-Territory DWI Acute Infarcts: Diagnostic Value in Cancer-Associated Hypercoagulation Stroke (Trousseau Syndrome). AJNR Am J Neuroradiol 2016; 37:2033-2036. [PMID: 27365322 DOI: 10.3174/ajnr.a4846] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 04/28/2016] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE DWI infarcts involving the bilateral anterior and posterior circulation suggest an embolic etiology. In the absence of an identifiable embolic source, we analyzed DWI lesions involving these 3 cerebral territories to determine the diagnostic value for ischemic infarction caused by cancer-associated hypercoagulation. MATERIALS AND METHODS A retrospective analysis of all brain MR imaging studies at our institution from July 2014 to June 2015 was conducted, yielding 4075 studies. Of those, 17% (n = 709) contained the terms "restricted-diffusion" plus either "numerous," "innumerable," "multiple," or "bilateral." Of these 709 reports, 6% (n = 41) of DWI lesions involving 3 or more vascular territories of the bilateral anterior and posterior circulation were analyzed. RESULTS Of the 41 patients, 19 separate etiologies were identified, the most frequent being malignancy-related infarctions (22% [n = 9]) and hypoxic-ischemic injury (12% [n = 5]). Only 2 patients had an indeterminate etiology. The most frequent etiology of infarctions not suspected clinically or radiographically was malignancy (P < .001). Infarctions of malignancy had a characteristic appearance, being nonenhancing, nonring-appearing clusters or single areas of restricted diffusion of 0.5-2 cm with a peripheral location or larger vascular territories, uncommonly in a watershed distribution, and with absence of diffuse cortical ribbon or deep gray nuclei involvement. CONCLUSIONS Approximately 1 in 5 ischemic infarcts in patients with DWI lesions involving 3 vessel territories are malignancy related. In the absence of an identifiable embolic source, ischemic infarction with cancer-associated hypercoagulation accounts for 75% of cases. Cancer-associated hypercoagulation infarction should be considered, particularly when no other cause is apparent.
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Affiliation(s)
- P F Finelli
- From the Department of Neurology, Hartford Hospital and University of Connecticut School of Medicine, Hartford, Connecticut.
| | - A Nouh
- From the Department of Neurology, Hartford Hospital and University of Connecticut School of Medicine, Hartford, Connecticut
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