Pub Date : 2024-08-21DOI: 10.1007/s12028-024-02099-8
Megan E Barra, Elizabeth K Zink, Thomas P Bleck, Eder Cáceres, Salia Farrokh, Brandon Foreman, Emilio Garzón Cediel, J Claude Hemphill, Masao Nagayama, DaiWai M Olson, Jose I Suarez
{"title":"Correction: Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Hospital Course, Confounders, and Medications.","authors":"Megan E Barra, Elizabeth K Zink, Thomas P Bleck, Eder Cáceres, Salia Farrokh, Brandon Foreman, Emilio Garzón Cediel, J Claude Hemphill, Masao Nagayama, DaiWai M Olson, Jose I Suarez","doi":"10.1007/s12028-024-02099-8","DOIUrl":"https://doi.org/10.1007/s12028-024-02099-8","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20DOI: 10.1007/s12028-024-02087-y
Sam Van Roy, Liangge Hsu, Joseph Ho, Benjamin M Scirica, David Fischer, Samuel B Snider, Jong Woo Lee
Background: Although magnetic resonance imaging, particularly diffusion-weighted imaging, has increasingly been used as part of a multimodal approach to prognostication in patients who are comatose after cardiac arrest, the performance of quantitative analysis of apparent diffusion coefficient (ADC) maps, as compared to standard radiologist impression, has not been well characterized. This retrospective study evaluated quantitative ADC analysis to the identification of anoxic brain injury by diffusion abnormalities on standard clinical magnetic resonance imaging reports.
Methods: The cohort included 204 previously described comatose patients after cardiac arrest. Clinical outcome was assessed by (1) 3-6 month post-cardiac-arrest cerebral performance category and (2) coma recovery to following commands. Radiological evaluation was obtained from clinical reports and characterized as diffuse, cortex only, deep gray matter structures only, or no anoxic injury. Quantitative analyses of ADC maps were obtained in specific regions of interest (ROIs), whole cortex, and whole brain. A subgroup analysis of 172 was performed after eliminating images with artifacts and preexisting lesions.
Results: Radiological assessment outperformed quantitative assessment over all evaluated regions (area under the curve [AUC] 0.80 for radiological interpretation and 0.70 for the occipital region, the best performing ROI, p = 0.011); agreement was substantial for all regions. Radiological assessment still outperformed quantitative analysis in the subgroup analysis, though by smaller margins and with substantial to near-perfect agreement. When assessing for coma recovery only, the difference was no longer significant (AUC 0.83 vs. 0.81 for the occipital region, p = 0.70).
Conclusions: Although quantitative analysis eliminates interrater differences in the interpretation of abnormal diffusion imaging and avoids bias from other prediction modalities, clinical radiologist interpretation has a higher predictive value for outcome. Agreement between radiological and quantitative analysis improved when using high-quality scans and when assessing for coma recovery using following commands. Quantitative assessment may thus be more subject to variability in both clinical management and scan quality than radiological assessment.
{"title":"Quantitative and Radiological Assessment of Post-cardiac-Arrest Comatose Patients with Diffusion-Weighted Magnetic Resonance Imaging.","authors":"Sam Van Roy, Liangge Hsu, Joseph Ho, Benjamin M Scirica, David Fischer, Samuel B Snider, Jong Woo Lee","doi":"10.1007/s12028-024-02087-y","DOIUrl":"https://doi.org/10.1007/s12028-024-02087-y","url":null,"abstract":"<p><strong>Background: </strong>Although magnetic resonance imaging, particularly diffusion-weighted imaging, has increasingly been used as part of a multimodal approach to prognostication in patients who are comatose after cardiac arrest, the performance of quantitative analysis of apparent diffusion coefficient (ADC) maps, as compared to standard radiologist impression, has not been well characterized. This retrospective study evaluated quantitative ADC analysis to the identification of anoxic brain injury by diffusion abnormalities on standard clinical magnetic resonance imaging reports.</p><p><strong>Methods: </strong>The cohort included 204 previously described comatose patients after cardiac arrest. Clinical outcome was assessed by (1) 3-6 month post-cardiac-arrest cerebral performance category and (2) coma recovery to following commands. Radiological evaluation was obtained from clinical reports and characterized as diffuse, cortex only, deep gray matter structures only, or no anoxic injury. Quantitative analyses of ADC maps were obtained in specific regions of interest (ROIs), whole cortex, and whole brain. A subgroup analysis of 172 was performed after eliminating images with artifacts and preexisting lesions.</p><p><strong>Results: </strong>Radiological assessment outperformed quantitative assessment over all evaluated regions (area under the curve [AUC] 0.80 for radiological interpretation and 0.70 for the occipital region, the best performing ROI, p = 0.011); agreement was substantial for all regions. Radiological assessment still outperformed quantitative analysis in the subgroup analysis, though by smaller margins and with substantial to near-perfect agreement. When assessing for coma recovery only, the difference was no longer significant (AUC 0.83 vs. 0.81 for the occipital region, p = 0.70).</p><p><strong>Conclusions: </strong>Although quantitative analysis eliminates interrater differences in the interpretation of abnormal diffusion imaging and avoids bias from other prediction modalities, clinical radiologist interpretation has a higher predictive value for outcome. Agreement between radiological and quantitative analysis improved when using high-quality scans and when assessing for coma recovery using following commands. Quantitative assessment may thus be more subject to variability in both clinical management and scan quality than radiological assessment.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02073-4
Kuntal Sen, Dana Harrar, Nicole Pariseau, Karis Tucker, Julia Keenan, Anqing Zhang, Andrea Gropman
Background: Acute metabolic crises in inborn errors of metabolism (such as urea cycle disorders, organic acidemia, maple syrup urine disease, and mitochondrial disorders) are neurological emergencies requiring management in the pediatric intensive care unit (PICU). There is a paucity of data pertaining to electroencephalograms (EEG) characteristics in this cohort. We hypothesized that the incidence of background abnormalities and seizures in this cohort would be high. Neuromonitoring data from our center's PICU over 10 years are presented in this article.
Methods: Data were collected by retrospective chart review for patients with the aforementioned disorders who were admitted to the PICU at our institution because of metabolic/neurologic symptoms from 2008 to 2018. Descriptive statistics (χ2 test or Fisher's exact test) were used to study the association between EEG parameters and outcomes.
Results: Our cohort included 40 unique patients (8 with urea cycle disorder, 7 with organic acidemia, 3 with maple syrup urine disease, and 22 with mitochondrial disease) with 153 admissions. Presenting symptoms included altered mentation (36%), seizures (41%), focal weakness (5%), and emesis (28%). Continuous EEG was ordered in 34% (n = 52) of admissions. Twenty-three admissions were complicated by seizures, including eight manifesting as status epilepticus (seven nonconvulsive and one convulsive). Asymmetry and focal slowing on EEG were associated with seizures. Moderate background slowing or worse was noted in 75% of EEGs. Among those patients monitored on EEG, 4 (8%) died, 3 (6%) experienced a worsening of their Pediatric Cerebral Performance Category (PCPC) score as compared to admission, and 44 (86%) had no change (or improvement) in their PCPC score during admission.
Conclusions: This study shows a high incidence of clinical and subclinical seizures during metabolic crisis in patients with inborn errors of metabolism. EEG background features were associated with risk of seizures as well as discharge outcomes. This is the largest study to date to investigate EEG features and risk of seizures in patients with neurometabolic disorders admitted to the PICU. These data may be used to inform neuromonitoring protocols to improve mortality and morbidity in inborn errors of metabolism.
{"title":"Seizure Characteristics and EEG Features in Intoxication Type and Energy Deficiency Neurometabolic Disorders in the Pediatric Intensive Care Unit: Single-Center Experience Over 10 Years.","authors":"Kuntal Sen, Dana Harrar, Nicole Pariseau, Karis Tucker, Julia Keenan, Anqing Zhang, Andrea Gropman","doi":"10.1007/s12028-024-02073-4","DOIUrl":"https://doi.org/10.1007/s12028-024-02073-4","url":null,"abstract":"<p><strong>Background: </strong>Acute metabolic crises in inborn errors of metabolism (such as urea cycle disorders, organic acidemia, maple syrup urine disease, and mitochondrial disorders) are neurological emergencies requiring management in the pediatric intensive care unit (PICU). There is a paucity of data pertaining to electroencephalograms (EEG) characteristics in this cohort. We hypothesized that the incidence of background abnormalities and seizures in this cohort would be high. Neuromonitoring data from our center's PICU over 10 years are presented in this article.</p><p><strong>Methods: </strong>Data were collected by retrospective chart review for patients with the aforementioned disorders who were admitted to the PICU at our institution because of metabolic/neurologic symptoms from 2008 to 2018. Descriptive statistics (χ<sup>2</sup> test or Fisher's exact test) were used to study the association between EEG parameters and outcomes.</p><p><strong>Results: </strong>Our cohort included 40 unique patients (8 with urea cycle disorder, 7 with organic acidemia, 3 with maple syrup urine disease, and 22 with mitochondrial disease) with 153 admissions. Presenting symptoms included altered mentation (36%), seizures (41%), focal weakness (5%), and emesis (28%). Continuous EEG was ordered in 34% (n = 52) of admissions. Twenty-three admissions were complicated by seizures, including eight manifesting as status epilepticus (seven nonconvulsive and one convulsive). Asymmetry and focal slowing on EEG were associated with seizures. Moderate background slowing or worse was noted in 75% of EEGs. Among those patients monitored on EEG, 4 (8%) died, 3 (6%) experienced a worsening of their Pediatric Cerebral Performance Category (PCPC) score as compared to admission, and 44 (86%) had no change (or improvement) in their PCPC score during admission.</p><p><strong>Conclusions: </strong>This study shows a high incidence of clinical and subclinical seizures during metabolic crisis in patients with inborn errors of metabolism. EEG background features were associated with risk of seizures as well as discharge outcomes. This is the largest study to date to investigate EEG features and risk of seizures in patients with neurometabolic disorders admitted to the PICU. These data may be used to inform neuromonitoring protocols to improve mortality and morbidity in inborn errors of metabolism.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02054-7
Rianne G F Dolmans, Jason Barber, Brandon Foreman, Nancy R Temkin, David O Okwonko, Claudia S Robertson, Geoffrey T Manley, Eric S Rosenthal
Background: Interventions to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI) are multimodal but variable, including sedation-dosing strategies. This article quantifies the different sedation intensities administered in patients with moderate to severe TBI (msTBI) using the therapy intensity level (TIL) across different intensive care units (ICUs), including the use of additional ICP-lowering therapies.
Methods: Within the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, we performed a retrospective analysis of adult patients with msTBI admitted to an ICU for a least 5 days from seven US level 1 trauma centers who received invasive ICP monitoring and intravenous sedation. Sedation intensity was classified prospectively as one of three ordinal levels as part of the validated TIL score, which were collected at least once a day.
Results: A total of 127 patients met inclusion criteria (mean age 41.6 ± 17.7 years; 20% female). The median Injury Severity Score was 27 (interquartile range 17-33), with a median admission Glasgow Coma Score of 3 (interquartile range 3-7); 104 patients had severe TBI (82%), and 23 patients had moderate TBI (18%). The sedation intensity score was highest on the first ICU day (2.69 ± 1.78), independent of patient severity. Time to reaching each sedation intensity level varied by site. Sedation level I was reached within 24 h for all sites, but sedation levels II and III were reached variably between days 1 and 3. Sedation level III was never reached by two of seven sites. The total TIL score was highest on the first ICU day, with a modest decrease for each subsequent ICU day, but there was high site-specific practice-pattern variation.
Conclusions: Intensity of sedation and other therapies for elevated ICP for patients with msTBI demonstrate large practice-pattern variation across level 1 trauma centers within the TRACK-TBI cohort study, independent of patient severity. Optimizing sedation strategies using patient-specific physiologic and pathoanatomic information may optimize patient outcomes.
背景:降低创伤性脑损伤(TBI)患者颅内压(ICP)的干预措施是多模式的,但也是多变的,其中包括镇静剂量策略。本文使用不同重症监护病房(ICU)的治疗强度级别(TIL)量化了中重度创伤性脑损伤(msTBI)患者所使用的不同镇静强度,包括额外ICP降低疗法的使用情况:在前瞻性的 TBI 研究与临床知识转化(TRACK-TBI)研究中,我们对来自美国 7 家一级创伤中心、入住 ICU 至少 5 天、接受有创 ICP 监测和静脉镇静治疗的 msTBI 成年患者进行了回顾性分析。镇静强度被前瞻性地划分为三个序数等级之一,作为有效TIL评分的一部分,每天至少收集一次:共有 127 名患者符合纳入标准(平均年龄为 41.6 ± 17.7 岁;20% 为女性)。受伤严重程度评分中位数为 27(四分位间范围为 17-33),入院格拉斯哥昏迷评分中位数为 3(四分位间范围为 3-7);104 名患者为重度创伤性脑损伤(82%),23 名患者为中度创伤性脑损伤(18%)。镇静强度评分在重症监护室第一天最高(2.69 ± 1.78),与患者的严重程度无关。达到各镇静强度等级的时间因部位而异。所有医院都在 24 小时内达到镇静强度 I 级,但镇静强度 II 级和 III 级在第 1 天和第 3 天之间达到的时间各不相同。7 个治疗点中有 2 个从未达到镇静强度 III 级。重症监护室第一天的 TIL 总分最高,随后每一天的总分都略有下降,但具体地点的实践模式差异很大:结论:在TRACK-TBI队列研究中,各一级创伤中心对msTBI患者ICP升高的镇静强度和其他治疗方法显示出很大的实践模式差异,这与患者的严重程度无关。利用患者特异性生理和病理解剖信息优化镇静策略可优化患者预后。
{"title":"Sedation Intensity in Patients with Moderate to Severe Traumatic Brain Injury in the Intensive Care Unit: A TRACK-TBI Cohort Study.","authors":"Rianne G F Dolmans, Jason Barber, Brandon Foreman, Nancy R Temkin, David O Okwonko, Claudia S Robertson, Geoffrey T Manley, Eric S Rosenthal","doi":"10.1007/s12028-024-02054-7","DOIUrl":"10.1007/s12028-024-02054-7","url":null,"abstract":"<p><strong>Background: </strong>Interventions to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI) are multimodal but variable, including sedation-dosing strategies. This article quantifies the different sedation intensities administered in patients with moderate to severe TBI (msTBI) using the therapy intensity level (TIL) across different intensive care units (ICUs), including the use of additional ICP-lowering therapies.</p><p><strong>Methods: </strong>Within the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, we performed a retrospective analysis of adult patients with msTBI admitted to an ICU for a least 5 days from seven US level 1 trauma centers who received invasive ICP monitoring and intravenous sedation. Sedation intensity was classified prospectively as one of three ordinal levels as part of the validated TIL score, which were collected at least once a day.</p><p><strong>Results: </strong>A total of 127 patients met inclusion criteria (mean age 41.6 ± 17.7 years; 20% female). The median Injury Severity Score was 27 (interquartile range 17-33), with a median admission Glasgow Coma Score of 3 (interquartile range 3-7); 104 patients had severe TBI (82%), and 23 patients had moderate TBI (18%). The sedation intensity score was highest on the first ICU day (2.69 ± 1.78), independent of patient severity. Time to reaching each sedation intensity level varied by site. Sedation level I was reached within 24 h for all sites, but sedation levels II and III were reached variably between days 1 and 3. Sedation level III was never reached by two of seven sites. The total TIL score was highest on the first ICU day, with a modest decrease for each subsequent ICU day, but there was high site-specific practice-pattern variation.</p><p><strong>Conclusions: </strong>Intensity of sedation and other therapies for elevated ICP for patients with msTBI demonstrate large practice-pattern variation across level 1 trauma centers within the TRACK-TBI cohort study, independent of patient severity. Optimizing sedation strategies using patient-specific physiologic and pathoanatomic information may optimize patient outcomes.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02076-1
Paul Vermilion, Renee Boss
Pediatric neurocritical care teams care for patients and families facing the potential for significant neurologic impairment and high mortality. Such admissions are often marked by significant prognostic uncertainty, high levels of parental emotional overload, and multiple potentially life-altering decision points. In addition to clinical acumen, families desire clear and consistent communication, supported decision-making, a multidisciplinary approach to psychosocial supports throughout an admission, and comprehensive bereavement support after a death. Distinct from their adult counterparts, pediatric providers care for a broader set of rare diagnoses with limited prognostic information. Decision-making requires its own ethical framework, with substitutive judgment giving way to the best interest standard as well as "good parent" narratives. When a child dies, bereavement support is often needed for the broader community. There will always be a role for specialist palliative care consultation in the pediatric neurocritical care unit, but the care of every patient and family will be well served by improving these primary palliative care skills.
{"title":"Pediatric Perspectives on Palliative Care in the Neurocritical Care Unit.","authors":"Paul Vermilion, Renee Boss","doi":"10.1007/s12028-024-02076-1","DOIUrl":"https://doi.org/10.1007/s12028-024-02076-1","url":null,"abstract":"<p><p>Pediatric neurocritical care teams care for patients and families facing the potential for significant neurologic impairment and high mortality. Such admissions are often marked by significant prognostic uncertainty, high levels of parental emotional overload, and multiple potentially life-altering decision points. In addition to clinical acumen, families desire clear and consistent communication, supported decision-making, a multidisciplinary approach to psychosocial supports throughout an admission, and comprehensive bereavement support after a death. Distinct from their adult counterparts, pediatric providers care for a broader set of rare diagnoses with limited prognostic information. Decision-making requires its own ethical framework, with substitutive judgment giving way to the best interest standard as well as \"good parent\" narratives. When a child dies, bereavement support is often needed for the broader community. There will always be a role for specialist palliative care consultation in the pediatric neurocritical care unit, but the care of every patient and family will be well served by improving these primary palliative care skills.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02086-z
Samuel D Jacobson, Vedant Kansara, Stephanie Assuras, Qi Shen, Lucie Kruger, Jerina Carmona, You Lim Song, Lizbeth Cespedes, Mariam Yazdi, Angela Velazquez, Ian Gonzales, Satoshi Egawa, E Sander Connolly, Shivani Ghoshal, David Roh, Sachin Agarwal, Soojin Park, Jan Claassen
Background: Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing.
Methods: We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4).
Results: Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01).
Conclusions: Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.
{"title":"Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.","authors":"Samuel D Jacobson, Vedant Kansara, Stephanie Assuras, Qi Shen, Lucie Kruger, Jerina Carmona, You Lim Song, Lizbeth Cespedes, Mariam Yazdi, Angela Velazquez, Ian Gonzales, Satoshi Egawa, E Sander Connolly, Shivani Ghoshal, David Roh, Sachin Agarwal, Soojin Park, Jan Claassen","doi":"10.1007/s12028-024-02086-z","DOIUrl":"https://doi.org/10.1007/s12028-024-02086-z","url":null,"abstract":"<p><strong>Background: </strong>Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing.</p><p><strong>Methods: </strong>We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4).</p><p><strong>Results: </strong>Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01).</p><p><strong>Conclusions: </strong>Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02078-z
Katharina M Busl, Cameron R Smith, Andrea B Troxel, Maurizio Fava, Nicholas Illenberger, Ralisa Pop, Wenqing Yang, Luciola Martins Frota, Hanzhi Gao, Guogen Shan, Brian L Hoh, Carolina B Maciel
Background: Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores.
Methods: BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase.
Results: Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection).
Conclusions: The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.
{"title":"Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.","authors":"Katharina M Busl, Cameron R Smith, Andrea B Troxel, Maurizio Fava, Nicholas Illenberger, Ralisa Pop, Wenqing Yang, Luciola Martins Frota, Hanzhi Gao, Guogen Shan, Brian L Hoh, Carolina B Maciel","doi":"10.1007/s12028-024-02078-z","DOIUrl":"https://doi.org/10.1007/s12028-024-02078-z","url":null,"abstract":"<p><strong>Background: </strong>Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores.</p><p><strong>Methods: </strong>BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase.</p><p><strong>Results: </strong>Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection).</p><p><strong>Conclusions: </strong>The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02079-y
Fernanda Cristina Poscai Ribeiro, Nadine Vieira de Oliveira, Gabriela Regonha Coral, Alcântara Ramos de Assis César, Moisés Willian Aparecido Gonçalves, Erika Said Abu Egal, Kleber Fernando Pereira
Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.
{"title":"Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.","authors":"Fernanda Cristina Poscai Ribeiro, Nadine Vieira de Oliveira, Gabriela Regonha Coral, Alcântara Ramos de Assis César, Moisés Willian Aparecido Gonçalves, Erika Said Abu Egal, Kleber Fernando Pereira","doi":"10.1007/s12028-024-02079-y","DOIUrl":"10.1007/s12028-024-02079-y","url":null,"abstract":"<p><p>Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I<sup>2</sup> = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1007/s12028-024-02082-3
Florian P Martin, Thomas Goronflot, Jean D Moyer, Olivier Huet, Karim Asehnoune, Raphaël Cinotti, Pierre A Gourraud, Antoine Roquilly
Background: The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability.
Methods: We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model.
Results: Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model.
Conclusions: We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.
背景:创伤性脑损伤(TBI)患者的长期功能预后仍然具有挑战性。我们的目的是证明重症监护室(ICU)变量并不能有效预测中重度创伤性脑损伤(msTBI)幸存者6个月的功能预后,而主要与死亡率相关,这导致预测死亡率和严重残疾综合预后的模型存在死亡率偏差:我们分析了创伤性脑损伤患者多中心随机对照连续高渗疗法试验的数据,并使用机器学习方法和在重症监护室住院期间收集的基线特征和预测因子开发了预测模型。我们比较了模型对所有 msTBI 患者 6 个月二元格拉斯哥结果量表扩展(GOS-E)评分(不利 GOS-E 1-4 vs. 有利 GOS-E 5-8)、死亡率(GOS-E 1 vs. GOS-E 2-8 )和 msTBI 幸存者二元功能结果(重度残疾 GOS-E 2-4 vs. 中度至无残疾 GOS-E 5-8)的预测。我们使用混合数据的预测模型和因子分析研究了ICU变量与msTBI幸存者长期功能预后之间的联系,并在TBI临床试验预后和分析国际任务(IMPACT)模型上验证了我们的假设:结果:基于370名msTBI患者的数据和经典的重症监护室变量,对幸存者6个月预后的预测效率较低(接收者操作特征下的平均面积为0.52)。通过对混合数据图进行因子分析,我们证明了高方差 ICU 变量与毫秒创伤性脑损伤幸存者的预后无关(维度 1 的 p = 0.15,维度 2 的 p = 0.53),但主要与死亡率有关(p 结论):我们利用基于机器学习的预测模型证明,经典的重症监护室变量与死亡率密切相关,但与毫秒创伤性脑损伤幸存者的 6 个月预后无关,这导致在预测死亡率和严重残疾的综合预后时存在死亡率偏差。
{"title":"Predictive Models of Long-Term Outcome in Patients with Moderate to Severe Traumatic Brain Injury are Biased Toward Mortality Prediction.","authors":"Florian P Martin, Thomas Goronflot, Jean D Moyer, Olivier Huet, Karim Asehnoune, Raphaël Cinotti, Pierre A Gourraud, Antoine Roquilly","doi":"10.1007/s12028-024-02082-3","DOIUrl":"https://doi.org/10.1007/s12028-024-02082-3","url":null,"abstract":"<p><strong>Background: </strong>The prognostication of long-term functional outcomes remains challenging in patients with traumatic brain injury (TBI). Our aim was to demonstrate that intensive care unit (ICU) variables are not efficient to predict 6-month functional outcome in survivors with moderate to severe TBI (msTBI) but are mostly associated with mortality, which leads to a mortality bias for models predicting a composite outcome of mortality and severe disability.</p><p><strong>Methods: </strong>We analyzed the data from the multicenter randomized controlled Continuous Hyperosmolar Therapy in Traumatic Brain-Injured Patients trial and developed predictive models using machine learning methods and baseline characteristics and predictors collected during ICU stay. We compared our models' predictions of 6-month binary Glasgow Outcome Scale extended (GOS-E) score in all patients with msTBI (unfavorable GOS-E 1-4 vs. favorable GOS-E 5-8) with mortality (GOS-E 1 vs. GOS-E 2-8) and binary functional outcome in survivors with msTBI (severe disability GOS-E 2-4 vs. moderate to no disability GOS-E 5-8). We investigated the link between ICU variables and long-term functional outcomes in survivors with msTBI using predictive modeling and factor analysis of mixed data and validated our hypotheses on the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model.</p><p><strong>Results: </strong>Based on data from 370 patients with msTBI and classically used ICU variables, the prediction of the 6-month outcome in survivors was inefficient (mean area under the receiver operating characteristic 0.52). Using factor analysis of mixed data graph, we demonstrated that high-variance ICU variables were not associated with outcome in survivors with msTBI (p = 0.15 for dimension 1, p = 0.53 for dimension 2) but mostly with mortality (p < 0.001 for dimension 1), leading to a mortality bias for models predicting a composite outcome of mortality and severe disability. We finally identified this mortality bias in the IMPACT model.</p><p><strong>Conclusions: </strong>We demonstrated using machine learning-based predictive models that classically used ICU variables are strongly associated with mortality but not with 6-month outcome in survivors with msTBI, leading to a mortality bias when predicting a composite outcome of mortality and severe disability.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1007/s12028-024-02072-5
Seungyon Koh, Sungju Park, Mijin Lee, Hanki Kim, Won Jung Lee, Jae-Myeong Lee, Jun Young Choi
Background: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process.
Methods: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment.
Results: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period.
Conclusions: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.
{"title":"Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.","authors":"Seungyon Koh, Sungju Park, Mijin Lee, Hanki Kim, Won Jung Lee, Jae-Myeong Lee, Jun Young Choi","doi":"10.1007/s12028-024-02072-5","DOIUrl":"https://doi.org/10.1007/s12028-024-02072-5","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment.</p><p><strong>Results: </strong>Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period.</p><p><strong>Conclusions: </strong>Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}