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A Web Based Dynamic MANA Nomogram For Sun et al. BMC Neurology (2020) 20:360 https://doi.org/10.1186/s12883-020-01935-6 RESEARCH ARTICLE Open Access A web based dynamic MANA Nomogram for predicting the malignant cerebral edema in patients with large hemispheric infarction Wenzhe Sun1, Guo Li1, Yang Song2, Zhou Zhu1, Zhaoxia Yang3, Yuxi Chen4, Jinfeng Miao1, Xiaoyan Song1, Yan Lan1, Xiuli Qiu1, Suiqiang Zhu1* and Yebin Fan5* Abstract Background: For large hemispheric infarction (LHI), malignant cerebral edema (MCE) is a life-threatening complication with a mortality rate approaching 80%. Establishing a convenient prediction model of MCE after LHI is vital for the rapid identification of high-risk patients as well as for a better understanding of the potential mechanism underlying MCE. Methods: One hundred forty-two consecutive patients with LHI within 24 h of onset between January 1, 2016 and August 31, 2019 were retrospectively reviewed. MCE was defined as patient death or received decompressive hemicraniectomy (DHC) with obvious mass effect (≥ 5 mm midline shift or Basal cistern effacement). Binary logistic regression was performed to identify independent predictors of MCE. Independent prognostic factors were incorporated to build a dynamic nomogram for MCE prediction. Results: After adjusting for confounders, four independent factors were identified, including previously known atrial fibrillation (KAF), midline shift (MLS), National Institutes of Health Stroke Scale (NIHSS) and anterior cerebral artery (ACA) territory involvement. To facilitate the nomogram use for clinicians, we used the “Dynnom” package to build a dynamic MANA (acronym for MLS, ACA territory involvement, NIHSS and KAF) nomogram on web (http://www.MANA-nom. com) to calculate the exact probability of developing MCE. The MANA nomogram’s C-statistic was up to 0.887 ± 0.041 and the AUC-ROC value in this cohort was 0.887 (95%CI, 0.828 ~ 0.934). Conclusions: Independent MCE predictors included KAF, MLS, NIHSS, and ACA territory involvement. The dynamic MANA nomogram is a convenient, practical and effective clinical decision-making tool for predicting MCE after LHI in Chinese patients. Keywords: Ischemic stroke, Large hemispheric infarction, Brain edema, Nomogram, Atrial fibrillation * Correspondence: [email protected]; [email protected] 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan 430030, China 5School of Computer Science and Technology, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan 430030, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sun et al. BMC Neurology (2020) 20:360 Page 2 of 8 Background retrospective study was approved by our Institutional Large hemispheric infarction (LHI) is a severe ischemic Review Board and the need for written informed con- stroke involving a large portion of MCA territory with sent was waived. LHI was defined as infarction in- significant morbidity and mortality [1]. For LHI, malig- volving ≥50% of the territory of the middle cerebral nant cerebral edema (MCE) is a life-threatening compli- artery (MCA) in computed tomography (CT) scan or cation with a mortality rate approaching 80% [2, 3]. DWI infarct volume > 82 mL within 24 h of onset [19]. MCE is characterized by a malignant course of rapid Infarct volume was calculated using the ABC/2 for- neurological deterioration associated with massive cere- mula [20]. MCE was defined as patient death or re- bral swelling between the second and fifth day after ceived DHC with obvious mass effect on follow-up stroke onset [4, 5], subsequent increased intracranial imaging examination (≥ 5 mm midline shift or Basal pressure (ICP), midline shift and brain herniation. To cistern effacement on CT or DWI). Patients were se- date, effective conservative treatment of MCE remains lected for DHC at our institution based on the cri- unsolved [6]. Moreover, treatment for MCE had largely teria outlined in previously published trials [21]. All focused on symptomatic patients rather than on edema patients completed the baseline CT scan or DWI at prevention. Given the exceptionally high mortality rate admission and had no primary intracranial associated with MCE, understanding the underlying hemorrhage. Other inclusion criteria for our study mechanisms and predictors in patients with MCE, were: 1) Chinese ethnicity; 2) age ≥ 18 years; 3) first or thereby enabling the identification of patients who will recurrent acute stroke occurring within 24 h before benefit from early intervention and providing effective admission. The exclusion criteria included: 1) Patients approaches for preventing MCE, are important. with terminal illness such as tumor, severe trauma, or Previous clinical research has indicated demographic, other life-threatening diseases before admission; 2) clinical and radiographic predictors for MCE [7–10]. Re- patients without follow-up imaging examinations (CT ported predictors of MCE included younger age, higher scanorDWI)24hafteronset;3)deathwithsecond- National Institutes of Health Stroke Scale (NIHSS) [7], ary intracranial hemorrhage, acute myocardial infarc- larger parenchymal hypoattenuation on computed tom- tion (AMI) or severe infection during hospitalization. ography (CT) [11], hyperdense artery sign and higher blood glucose [10]. In recent years, diffusion weighted imaging (DWI) has been extensively used for MCE pre- Data collection diction [7, 9]. However, these indicators are not precise Admission characteristics were recorded for all patients, enough, not easy to obtain, or their predictive role in consisting of age, gender, smoking and drinking history, clinical settings is limited by their hysteresis [12]. Mean- preexisting hypertension, diabetes mellitus, previous while, most known predictors are described in the West- stroke, preexisting coronary heart disease, admission ern context. Although China has experienced rapid temperature, admission systolic pressure and admission health transitions over the last four decades, the lifetime diastolic pressure and previous atrial fibrillation (AF). risk of stroke in China is significantly higher than the AF was identified as previously known AF (KAF), differ- global average [13]. With stroke being the first cause of entiating from AF detected after stroke (AFDAS) [22]. death in China [14]. Hence, MCE in Chinese patients is Recorded treatments included intravenous thrombolysis worth exploring. or endovascular intervention. Laboratory tests on admis- Furthermore, traditional MCE scoring models enrolled sion included baseline fasting blood glucose (FBG) and NHISS and MLS as categorical variables for its conveni- HbA1c. All 142 patients underwent CT/DWI within 24 ence by clinical use, which may end up degrading preci- h of onset and the imaging data were evaluated by two sion [15–18]. Nomograms can get rid of that limitation experienced clinicians, blinded to the patients’ outcome. but are not as clinically accessible as scoring models. Mo- Midline shift (MLS) was defined as the distance from tivated by the above facts, we sought to establish a web- the septum pellucida to the anatomic line anchored by based nomogram, with balanced precision and practicabil- the falx cerebri to the skull. Stroke severity was mea- ity, to forecast MCE in Chinese patients with LHI. sured using the National Institutes of Health stroke scale (NIHSS). Cases without recorded NIHSS (N = 127, Methods 89.4%) were not excluded from analysis. The NIHSS Patient selection scores of all patients in this study were assessed by two This study continuously enrolled 157 adult patients experienced raters according to the patient’s admission diagnosed with LHI and admitted within 24 h to the documented neurologic exams. All raters were blinded neuro-intensive care unit (NICU) of Tongji Hospital to the patients’ outcome. An intra-rater reliability test at Huazhong University of Science and Technology was performed in 50 subjects, and the kappa values for between January 2016 and August 2019. This MLS and NIHSS are 0.88 and 0.80, respectively. Sun et al. BMC Neurology (2020) 20:360 Page 3 of 8 Statistical analysis 0.05. All P-values were two-sided, P < 0.05 was con- Statistical analyses were performed using IBM SPSS sidered statistically significant. Collinearity of variables Statistics 22.0 (SPSS Inc., Chicago, IL, United States) that entered the multivariate logistic regression
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