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Manish N. Shah, Ivan T. Stoev, Dominic E. Sanford, Feng Gao, Paul Santiago, David P. Jaques, and Ralph G. Dacey Jr.

Object

The goal of this study was to examine the reasons for early readmissions within 30 days of discharge to a major academic neurosurgical service.

Methods

A database of readmissions within 30 days of discharge between April 2009 and September 2010 was retrospectively reviewed. Clinical and administrative variables associated with readmission were examined, including age, sex, race, days between discharge and readmission, and insurance type. The readmissions were then assigned independently by 2 neurosurgeons into 1 of 3 categories: scheduled, adverse event, and unrelated. The adverse event readmissions were further subcategorized into patients readmitted although best practices were followed, those readmitted due to progression of their underlying disease, and those readmitted for preventable causes. These variables were compared descriptively.

Results

A total of 348 patients with 407 readmissions were identified, comprising 11.5% of the total 3552 admissions. The median age of readmitted patients was 55 years (range 16–96 years) and patients older than 65 years totaled 31%. There were 216 readmissions (53% of 407) for management of an adverse event that was classified as either preventable (149 patients; 37%) or unpreventable (67 patients; 16%). There were 113 patients (28%) who met readmission criteria but who were having an electively scheduled neurosurgical procedure. Progression of disease (48 patients; 12%) and treatment unrelated to primary admission (30 patients; 7%) were additional causes for readmission. There was no significant difference in the proportion of early readmissions by payer status when comparing privately insured patients and those with public or no insurance (p = 0.09).

Conclusions

The majority of early readmissions within 30 days of discharge to the neurosurgical service were not preventable. Many of these readmissions were for adverse events that occurred even though best practices were followed, or for progression of the natural history of the neurosurgical disease requiring expected but unpredictably timed subsequent treatment. Judicious care often requires readmission to prevent further morbidity or death in neurosurgical patients, and penalties for readmission will not change these patient care obligations.

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Shu-Guang Gao, Guang-Hua Lei, Hong-Bo He, Hua Liu, Wen-Feng Xiao, Ting Wen, Jie-Yu Liang, and Kang-Hua Li

Object

With the increasing advocacy for total disc replacement (TDR) as a potential alternative to fusion in the management of lumbar degenerative disc disease, intradiscal pressures (IDPs) and facet joint stresses at the adjacent levels of spine have generated considerable interest. The purpose of this study was to compare adjacent-level IDPs and facet joint stresses among TDR, discectomy, and fusion.

Methods

Ten fresh human cadaveric lumbar specimens (L2–S1) were subjected to an unconstrained load in axial torsion, lateral bending, flexion, and extension by using multidirectional flexibility test. Four surgical treatment modes—control (disc intact), discectomy, TDR, and fusion—were tested in sequential order at L4–5. During testing, the IDPs and facet forces following each treatment were calculated at the adjacent vertebral levels (L3–4 and L5–S1).

Results

Intradiscal pressures and facet force pressures were similar between the intact condition and the TDR reconstruction at the L3–4 and L5–S1 levels under all loading conditions (p > 0.05). Compared with the intact and TDR groups, the discectomy and fusion groups had higher IDPs at the L3–4 and L5–S1 levels under all loading conditions (p < 0.05). No significant difference in the facet force pressure was noted among the intact, discectomy, and TDR groups at the L3–4 and L5–S1 levels under any loading conditions (p > 0.05). However, the facet force pressure produced for fusion was significantly higher than the mean values obtained for the intact, discectomy, and TDR groups at the L3–4 and L5–S1 levels under all loading conditions (p < 0.05).

Conclusions

Lumbar TDR maintained adjacent-level IDPs and facet force pressures near the values for intact spines, whereas adjacent-level IDPs tended to increase after discectomy or fusion and facet forces tended to increase after fusion.

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Bo Hou, Lu Gao, Lin Shi, Yishan Luo, Xiaopeng Guo, Geoffrey S. Young, Lei Qin, Huijuan Zhu, Lin Lu, Zihao Wang, Ming Feng, Xinjie Bao, Renzhi Wang, Bing Xing, and Feng Feng

OBJECTIVE

Cushing’s disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis.

METHODS

Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence–assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery.

RESULTS

Widespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05).

CONCLUSIONS

This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.

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Bo Hou, Lu Gao, Lin Shi, Yishan Luo, Xiaopeng Guo, Geoffrey S. Young, Lei Qin, Huijuan Zhu, Lin Lu, Zihao Wang, Ming Feng, Xinjie Bao, Renzhi Wang, Bing Xing, and Feng Feng

OBJECTIVE

Cushing’s disease (CD) involves brain impairments caused by excessive cortisol. Whether these impairments are reversible in remitted CD after surgery has long been controversial due to a lack of high-quality longitudinal studies. In this study the authors aimed to assess the reversibility of whole-brain changes in remitted CD after transsphenoidal surgery (TSS), and its correlations with clinical and hormonal parameters, in the largest longitudinal study cohort to date for CD patient brain analysis.

METHODS

Fifty patients with pathologically diagnosed CD and 36 matched healthy controls (HCs) were enrolled in a tertiary comprehensive hospital and national pituitary disease registry center in China. 3-T MRI studies were analyzed using an artificial intelligence–assisted web-based autosegmentation tool to quantify 3D brain volumes. Clinical parameters as well as levels of serum cortisol, adrenocorticotrophic hormone (ACTH), and 24-hour urinary free cortisol were collected for the correlation analysis. All CD patients underwent TSS and 46 patients achieved remission. All clinical, hormonal, and MRI parameters were reevaluated at the 3-month follow-up after surgery.

RESULTS

Widespread brain volume loss was observed in active CD patients compared with HCs, including total gray matter (p = 0.003, with false discovery rate [FDR] correction) and the frontal, parietal, occipital, and temporal lobes; insula; cingulate lobe; and enlargement of lateral and third ventricles (p < 0.05, corrected with FDR). All affected brain regions improved significantly after TSS (p < 0.05, corrected with FDR). In patients with remitted CD, total gray matter and most brain regions (except the frontal and temporal lobes) showed full recovery of volume, with volumes that did not differ from those of HCs (p > 0.05, corrected with FDR). ACTH and serum cortisol changes were negatively correlated with brain volume changes during recovery (p < 0.05).

CONCLUSIONS

This study demonstrates the rapid reversal of total gray matter loss in remitted CD. The combination of full recovery areas and partial recovery areas after TSS is consistent with the incomplete recovery of memory and cognitive function observed in CD patients in clinical practice. Correlation analyses suggest that ACTH and serum cortisol levels are reliable serum biomarkers of brain recovery for clinical use after surgery.

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Yifan Zhang, Xiongfei Wang, Chongyang Tang, Yuguang Guan, Fan Chen, Qing Gao, Jing Wang, Jian Zhou, Feng Zhai, Detlev Boison, Guoming Luan, and Tianfu Li

OBJECTIVE

Vagus nerve stimulation (VNS) is an alternative treatment option for individuals with refractory epilepsy, with nearly 40% of patients showing no benefit after VNS and only 6%–8% achieving seizure freedom. It is presently unclear why some patients respond to treatment and others do not. Therefore, identification of biomarkers to predict efficacy of VNS is of utmost importance. The objective of this study was to explore whether genetic variations in genes involved in adenosine kinase (ADK), ecto-5′-nucleotidase (NT5E), and adenosine A1 receptor (A1R) are linked to outcome of VNS in patients with refractory epilepsy.

METHODS

Thirty single-nucleotide polymorphisms (SNPs), including 9 in genes encoding ADK, 3 in genes encoding NT5E, and 18 in genes encoding A1R, were genotyped in 194 refractory epilepsy patients who underwent VNS. The chi-square test and binary logistic regression were used to determine associations between genetic differences and VNS efficacy.

RESULTS

A significant association between ADK SNPs rs11001109, rs7899674, and rs946185 and seizure reduction with VNS was found. Regardless of sex, age, seizure frequency and type, antiseizure drug use, etiology, and prior surgical history, all patients (10/10 patients [100%]) with minor allele homozygosity at rs11001109 (genotype AA) or rs946185 (AA) achieved > 50% seizure reduction and 4 patients (4/10 [40%]) achieved seizure freedom. VNS therapy demonstrated higher efficacy among carriers of minor allele rs7899674 (CG + GG) (68.3% vs 48.8% for patients with major allele homozygosity).

CONCLUSIONS

Homozygous ADK SNPs rs11001109 (AA) and rs946185 (AA), as well as minor allele rs7899674 (CG + GG), may serve as useful biomarkers for prediction of VNS therapy outcome.

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Ying Yu, Long Yan, Yake Lou, Rongrong Cui, Kaijiang Kang, Lingxian Jiang, Dapeng Mo, Feng Gao, Yongjun Wang, Xin Lou, Zhongrong Miao, and Ning Ma

OBJECTIVE

This study aimed to identify predictors of intracranial in-stent restenosis (ISR) after stent placement in symptomatic intracranial atherosclerotic stenosis (ICAS).

METHODS

The authors retrospectively collected data from consecutive patients who suffered from symptomatic ICAS and underwent successful stent placement in Beijing Tiantan hospital. Eligible patients were classified into “ISR,” “indeterminate ISR,” or “no-ISR” groups by follow-up digital subtraction angiography or CT angiography. A multivariate logistic regression model was used to explore the predictors of intracranial ISR after adjustments for age and sex. In addition, ISR and no-ISR patients were divided into two groups based on the strongest predictor, and the incidence of ISR, recurrent stroke, and symptomatic ISR was compared between the two groups.

RESULTS

A total of 511 eligible patients were included in the study: 80 ISR, 232 indeterminate ISR, and 199 no-ISR patients. Elevated high-sensitivity C-reactive protein (hs-CRP; odds ratio [OR] 4.747, 95% confidence interval [CI] 2.253–10.01, p < 0.001), Mori type B and C (Mori type B vs Mori type A, OR 3.119, 95% CI 1.093–8.896, p = 0.033; Mori type C vs Mori type A, OR 4.780, 95% CI 1.244–18.37, p = 0.023), coronary artery disease (CAD; OR 2.721, 95% CI 1.192–6.212, p = 0.017), neutrophil/lymphocyte ratio (NLR; OR 1.474 95% CI 1.064–2.042, p = 0.020), residual stenosis (OR 1.050, 95% CI 1.022–1.080, p = 0.001) and concurrent intracranial tandem stenosis (OR 2.276, 95% CI 1.039–4.986, p = 0.040) synergistically contributed to the occurrence of intracranial ISR. Elevated hs-CRP (hs-CRP ≥ 3 mg/L) was the strongest predictor for ISR, and the incidence of ISR in the elevated hs-CRP group and normal hs-CRP group (hs-CRP < 3 mg/L) was 57.14% versus 21.52%, respectively, with recurrent stroke 44.64% versus 16.59%, and symptomatic ISR 41.07% versus 8.52%.

CONCLUSIONS

Elevated hs-CRP level, NLR, residual stenosis, Mori type B and C, CAD, and concurrent intracranial tandem stenosis are the main predictors of intracranial ISR, and elevated hs-CRP is crucially associated with recurrent stroke in patients with symptomatic ICAS after intracranial stent implantation.

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Ming-liang Yang, Jian-jun Li, Shao-cheng Zhang, Liang-jie Du, Feng Gao, Jun Li, Yu-ming Wang, Hui-ming Gong, and Liang Cheng

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

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Xing Wu, Jin Hu, Liangfu Zhou, Ying Mao, Bojie Yang, Liang Gao, Rong Xie, Feng Xu, Dong Zhang, Jun Liu, and Jianhong Zhu

Object

Mesenchymal stem cells (MSCs) have been shown to migrate toward tumors, but their distribution pattern in gliomas has not been completely portrayed. The primary purpose of the study was to assay the tropism capacity of MSCs to gliomas, to delineate the pattern of MSC distribution in gliomas after systemic injection, and to track the migration and incorporation of magnetically labeled MSCs using 1.5-T magnetic resonance (MR) imaging.

Methods

The MSCs from Fischer 344 rats were colabeled with superparamagnetic iron oxide nanoparticles (SPIO) and enhanced green fluorescent protein (EGFP). The tropism capacity of MSCs was quantitatively assayed in vitro using the Transwell system. To track the migration of MSCs in vivo, MR imaging was performed both 7 and 14 days after systemic administration of labeled MSCs. After MR imaging, the distribution patterns of MSCs in rats with gliomas were examined using Prussian blue and fluorescence staining.

Results

The in vitro study showed that MSCs possessed significantly greater migratory capacity than fibroblast cells (p < 0.001) and that lysis of F98 glioma cells and cultured F98 cells showed a greater capacity to induce migration of cells than other stimuli (p < 0.05). Seven days after MSC transplantation, the SPIO–EGFP colabeled cells were distributed throughout the tumor, where a well-defined dark hypointense region was represented on gradient echo sequences. After 14 days, most of the colabeled MSCs were found at the border between the tumor and normal parenchyma, which was represented on gradient echo sequences as diluted amorphous dark areas at the edge of the tumors.

Conclusions

This study demonstrated that systemically transplanted MSCs migrate toward gliomas with high specificity in a temporal–spatial pattern, which can be tracked using MR imaging.

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Manish N. Shah, Jeffrey R. Leonard, Gabrielle Inder, Feng Gao, Michael Geske, Devon H. Haydon, Melvin E. Omodon, John Evans, Diego Morales, Ralph G. Dacey, Matthew D. Smyth, Michael R. Chicoine, and David D. Limbrick

Object

This study describes the pediatric experience with a dual-multifunction-room IMRIS 1.5-T intraoperative magnetic resonance imaging (iMRI) suite and analyzes its impact on clinical variables associated with neurosurgical resection of intracranial lesions, including safety and efficacy.

Methods

Since the inception of the iMRI–guided resection program in April 2008 at both Barnes-Jewish and St. Louis Children's Hospital, a prospective database recorded the clinical variables associated with demographics and outcome with institutional review board approval. A similarly approved retrospective database was constructed from February 2006 to March 2010 for non–iMRI resections. These databases were retrospectively reviewed for clinical variables associated with resection of pediatric (age 20 months–21 years) intracranial lesions including brain tumors and focal cortical dysplasia. Patient demographics, operative time, estimated blood loss, additional resection, length of stay, pathology, and complications were analyzed.

Results

The authors found that 42 iMRI–guided resections were performed, whereas 103 conventional resections had been performed without the iMRI. The mean patient age was 10.5 years (range 20 months–20 years) in the iMRI group and 9.8 years (range 2–21 years) in the conventional group (p = 0.41). The mean duration of surgery was 350 minutes in the iMRI group and 243 minutes in the conventional group (p < 0.0001). The mean hospital stay was 8.2 days in the iMRI group, and 6.6 days in the conventional group, and this trended toward significance (p = 0.05). In the first 2 weeks postoperatively, there were 8 reoperations (7.77%) in the conventional group compared with none in the iMRI group, which was not significant in a 2-tailed test (p = 0.11) but trended toward significance in a 1-tailed test (p = 0.06). The significant complications included reoperation for hydrocephalus or infection: 6.8% (conventional) versus 4.8% (iMRI).

Conclusions

Intraoperative MR imaging–guided resections resulted in a trend toward reduction in the need for repeat surgery in the immediate 2-week postoperative period compared with conventional pediatric neurosurgical resections for tumor or focal cortical dysplasia. Although there is an increased operative time, the iMRI suite offers a comparable safety and efficacy profile while potentially reducing the per-case cost by diminishing the need for early reoperation.

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Yuzaburo Shimizu, Joy Gumin, Feng Gao, Anwar Hossain, Elizabeth J. Shpall, Akihide Kondo, Brittany C. Parker Kerrigan, Jing Yang, Daniel Ledbetter, Juan Fueyo, Candelaria Gomez-Manzano, and Frederick F. Lang

OBJECTIVE

Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy.

METHODS

The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemotherapy. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs.

RESULTS

The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor–derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas.

CONCLUSIONS

The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.