bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting IL-13Rα2 for effective treatment of malignant peripheral nerve sheath tumors in mouse models
Authors: Mrowczynski Oliver D. , Payne Russell A. , Bourcier Alexandre J. , Mau Christine Y. , Slagle-Webb Becky , Shenoy Ganesh , Madhankumar Achuthamangalam B. , Abramson Stephan B. , Wolfe Darren , Harbaugh Kimberly S. , Rizk Elias B. , Connor James R. 
Published: February 2019

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that harbor a high potential for metastasis and have a devastating prognosis. Combination chemoradiation aids in tumor control and decreases tumor recurrence but causes deleterious side effects and does not extend long-term survival. An effective treatment with limited toxicity and enhanced efficacy is critical for patients suffering from MPNSTs.METHODSThe authors recently identified that interleukin-13 receptor alpha 2 (IL-13Rα2) is overexpressed on MPNSTs and could serve as a precision-based target for delivery of chemotherapeutic agents. In the work reported here, a recombinant fusion molecule consisting of a mutant human IL-13 targeting moiety and a point mutant variant of Pseudomonas exotoxin A (IL-13.E13 K-PE4E) was utilized to treat MPNST in vitro in cell culture and in an in vivo murine model.RESULTSIL-13.E13 K-PE4E had a potent cytotoxic effect on MPNST cells in vitro. Furthermore, intratumoral administration of IL-13.E13 K-PE4E to orthotopically implanted MPNSTs decreased tumor burden 6-fold and 11-fold in late-stage and early-stage MPNST models, respectively. IL-13.E13 K-PE4E treatment also increased survival by 23 days in the early-stage MPNST model.CONCLUSIONSThe current MPNST treatment paradigm consists of 3 prongs: surgery, chemotherapy, and radiation, none of which, either singly or in combination, are curative or extend survival to a clinically meaningful degree. The results presented here provide the possibility of intratumoral therapy with a potent and highly tumor-specific cytotoxin as a fourth treatment prong with the potential to yield improved outcomes in patients with MPNSTs.
Functional connectivity analysis and prediction of cognitive change after carotid artery stenting
Authors: Tani Naoki , Yaegaki Takahide , Nishino Akio , Fujimoto Kenta , Hashimoto Hiroyuki , Horiuchi Kaoru , Nishiguchi Mitsuhisa , Kishima Haruhiko 
Published: February 2019

OBJECTIVEThe neurocognitive course of patients who have undergone cerebral revascularization has been the subject of many studies, and the reported effects of carotid artery stenting (CAS) on cognitive function have varied from study to study. The authors hypothesized that cognitive amelioration after CAS is associated with alteration of the default mode network (DMN) connectivity, and they investigated the correlation between functional connectivity (FC) of the DMN and post-CAS changes in cognitive function in order to find a clinical marker that can be used to predict the effect of cerebral revascularization on patients’ cognitive function in this preliminary exploratory study.METHODSThe authors examined post-CAS changes in cognitive function in relation to FC in patients treated for unilateral carotid artery stenosis. Resting-state functional MRI (rs-fMRI) was performed with a 3-T scanner before and 6 months after CAS in 8 patients. Neuropsychological tests (Wechsler Adult Intelligence Scale III and Wechsler Memory Scale–Revised) were administered to each patient before and 6 months after CAS. The DMN was mapped for each patient through independent component analysis of the rs-fMR images, and the correlation between FC of the DMN and post-CAS change in cognitive function was analyzed on a voxel level. Multivariable regression analysis was performed to identify preoperative factors associated with a post-CAS change in cognitive function.RESULTSPost-CAS cognitive function varied between patients and between categories of neuropsychological tests. Although there was no significant overall improvement in Working Memory scores after CAS, post-CAS Working Memory scores changed in negative correlation with changes in FC between the DMN and the precentral/superior frontal gyrus and between the DMN and the middle frontal gyrus. In addition, the preoperative FC between those areas correlated positively with the post-CAS improvement in working memory.CONCLUSIONSFC between the DMN and working memory–related areas is closely associated with improvement in working memory after CAS. Preoperative analysis of FC of the DMN may be useful for predicting postoperative improvement in the working memory of patients being treated for unilateral stenosis of the extracranial internal carotid artery.Clinical trial registration no.: UMIN000020045 (www.umin.ac.jp/ctr/index.htm)
Clinically applicable delineation of the pallidal sensorimotor region in patients with advanced Parkinson’s disease: study of probabilistic and deterministic tractography
Authors: Muller Jennifer , Alizadeh Mahdi , Mohamed Feroze B. , Riley Jonathan , Pearce John J. , Trieu Benjamin , Liang Tsao-Wei , Romo Victor , Sharan Ashwini , Wu Chengyuan 
Published: February 2019

OBJECTIVEDeep brain stimulation (DBS) is an effective procedure in improving motor symptoms for patients with advanced Parkinson’s disease (PD) through the use of high-frequency stimulation. Although one of the most commonly used target sites for DBS, sensorimotor regions of the globus pallidus interna (GPi) have yet to be thoroughly described with advanced neuroimaging analysis in vivo for human subjects. Furthermore, many imaging studies to date have been performed in a research setting and bring into question the feasibility of their applications in a clinical setting, such as for surgical planning. This study compares two different tractography methods applied to clinically feasible acquisition sequences in identifying sensorimotor regions of the GPi and the subthalamic nucleus (STN) in patients with advanced PD selected to undergo DBS.METHODSSeven patients with refractory PD selected for DBS were examined by MRI. Diffusion images were acquired with an average acquisition time of 15 minutes. Probabilistic and deterministic tractography methods were applied to each diffusion-weighted data set using FSL and MRtrix, respectively. Fiber assignment was performed using combined sensorimotor areas as initiation seeds and the STN and GPi, separately, as inclusion masks. Corticospinal tracts were excluded by setting the cerebral peduncles as exclusion masks. Variability between proposed techniques was shown using center of gravity (CoG) coordinates.RESULTSDeterministic and probabilistic corticopallidal and corticosubthalamic pathways were successfully reconstructed for all subjects across all target sites (bilaterally). Both techniques displayed large connections between the sensorimotor cortex with the posterolateral aspect of the ipsilateral GPi and the posterosuperolateral aspect of the ipsilateral STN. The average variability was 2.67 mm, with the probabilistic method identifying the CoG consistently more posterior and more lateral than the deterministic method.CONCLUSIONSSuccessful delineation of the sensorimotor regions in both the GPi and STN is achievable within a clinically reasonable timeframe. The techniques described in this paper may enhance presurgical planning with increased accuracy and improvement of patient outcomes in patients undergoing DBS. The variability found between tracking techniques warrants the use of the probabilistic tractography method over the deterministic method for presurgical planning. Probabilistic tractography was found to have an advantage over deterministic tractography in its sensitivity, in accurately describing previously described tracts, and in its ability to detect a larger number of fibers.
Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: complications, aneurysm sac occlusion, reabsorption, recurrence, and jailed branch modification at follow-up
Authors: Michelozzi Caterina , Darcourt Jean , Guenego Adrien , Januel Anne-Christine , Tall Philippe , Gawlitza Matthias , Bonneville Fabrice , Cognard Christophe 
Published: February 2019

OBJECTIVEThe purpose of this study is to present the authors’ medium-term results, with special emphasis on complications, occlusion rate of the aneurysm sac (digital subtraction angiography [DSA] and MRI), and the fate of cortical branches and perforating arteries covered (“jailed”) by the flow diverter (FD) stent.METHODSBetween January 2010 and September 2017, 29 patients (14 female) with 30 aneurysms were treated with an FD stent. Twenty-one aneurysms were at the middle cerebral artery bifurcation, 8 were in the anterior communicating artery region, and 1 was a pericallosal artery bifurcation. Thirty-five cortical branches were covered. A single FD stent was used in all patients. Symptomatic and asymptomatic periprocedural and delayed complications were reported. DSA and MRI controls were analyzed to evaluate modification of the aneurysm sac and jailed branches.RESULTSPermanent morbidity was 3.4% (1/29), due to a jailed branch occlusion, with a modified Rankin Scale (mRS) score of 2 at the last follow-up. Mortality and permanent complication with poor prognosis (mRS score > 2) rates were 0%. The mean follow-up time for DSA and MRI (mean ± SD) was 21 ± 14.5 months (range 3–66 months) and 19 ± 16 months (range 3–41 months), respectively. The mean time to aneurysm sac occlusion (available for 24 patients), including stable remodeling, was 11.8 ± 6 months (median 13, range 3–27 months). The overall occlusion rate was 82.1% (23/28), and it was 91.7% (22/24) in the group of patients with at least 2 DSA control sequences. One recanalization occurred at 41 months posttreatment. At the time of publication, at the latest follow-up, 7 (20%) of 35 covered branches were occluded, 18 (51.4%) showed a decreased caliber, and the remaining 10 (28.5%) were unchanged. MRI T2-weighted sequences showed complete sac reabsorption in 7/29 aneurysms (24.1%), and the remaining lesions were either smaller (55.2%) or unchanged (17.2%). MRI revealed asymptomatic and symptomatic ischemic events in perforator territories in 7/28 (25%) and 4/28 (14.3%) patients, respectively, which were reversible within 24 hours.CONCLUSIONSFlow diversion of bifurcation aneurysms is feasible, with low rates of permanent morbidity and mortality and high occlusion rates; however, recurrence may occur. Caliber reduction and asymptomatic occlusion of covered cortical branches as well as silent perforator stroke are common. Ischemic complications may occur with no identified predictable factors. MRI controls should be required in all patients to evaluate silent ischemic lesions and aneurysm sac reabsorption over time.
Biomechanics of a novel reversibly expandable dynamic craniotomy bone flap fixation plate
Authors: Khanna Rohit , Ferrara Lisa , Khanna Sohit 
Published: February 2019

OBJECTIVEBiomechanical evaluation of a novel expandable cranial fixation plate was assessed in cadavers. The dynamic craniotomy procedure uses low-profile reversibly expandable plates that allow cranial decompression by providing for intracranial volume expansion without removal of the bone flap. The plates allow reversible outward movement of the bone flap upon an increase in intracranial pressure (ICP) and also retract the bone flap and prevent it from sinking inside the cranium once the ICP normalizes.METHODSA comparative evaluation of the extent of ICP control with an increase in intracranial volume between various bone flap fixation techniques was undertaken along with testing of the expandable plate compliance. Static compression tests of the plates were performed to assess bone flap fixation and prevention of sinking. Quasi-static shear tension testing of the plates was undertaken to test the tolerance of the plates for expansion. Fatigue shear tension evaluation of the plates was undertaken to assess tolerance for repetitive expansion and contraction.RESULTSThe dynamic craniotomy provided superior control of ICP with an increase in intracranial volume compared to the hinged craniotomy and standard craniotomy techniques (p < 0.001). Static compression results revealed that the plates withstood bone flap sinkage with a mean peak load of 643.3 ± 26.1 N and a mean inward bone flap displacement of 1.92 ± 0.09 mm. Static shear tension results indicated that the plates could withstand a peak expansion of 71.6 mm. Dynamic shear tension testing of the plates with repetitive 15-mm outward expansion and retraction for a total of up to 500 cycles revealed no cracking and no failure points.CONCLUSIONSThe reversibly expandable plates provide for a low-profile bone flap fixation with rigid restriction of bone flap sinking and also enable cranial decompression with a high tolerance for repetitive expansion and contraction.
Comparative effectiveness analysis of Pipeline device versus coiling in unruptured aneurysms smaller than 10 mm
Authors: Malhotra Ajay , Wu Xiao , Miller Timothy , Matouk Charles C. , Sanelli Pina , Gandhi Dheeraj 
Published: February 2019

OBJECTIVEBoth endovascular coiling and the Pipeline embolization device (PED) have been shown to be safe and clinically effective for treatment of small (< 10 mm) aneurysms. The authors conducted a comparative effectiveness analysis to compare the utility of these treatment methods in terms of health benefits.METHODSA decision-analytical study was performed with Markov modeling methods to simulate patients with small unruptured aneurysms undergoing endovascular coiling, stent-assisted coiling (SAC), or PED placement for treatment. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses were performed to assess model and input parameter uncertainty.RESULTSThe base case calculation for a 50-year-old man reveals PED to have a higher health benefit (17.48 quality-adjusted life years [QALYs]) than coiling (17.44 QALYs) or SAC (17.36 QALYs). PED is the better option in 6020 of the 10,000 iterations in probabilistic sensitivity analysis. When the retreatment rate of PED is lower than 9.53%, and the coiling retreatment is higher than 15.6%, PED is the better strategy. In the 2-way sensitivity analysis varying the retreatment rates from both treatment modalities, when the retreatment rate of PED is approximately 14% lower than the retreatment rate of coiling, PED is the more favorable treatment strategy. Otherwise, coiling is more effective. SAC may be better than PED when the unfavorable outcome risk of SAC is lower than 70% of its reported current value.CONCLUSIONSWith the increasing use of PEDs for treatment of small unruptured aneurysms, the current study indicates that these devices may have higher health benefits due to lower rates of retreatment compared to both simple coiling and stent-assisted techniques. Longer follow-up studies are needed to document the rates of recurrence and retreatment after coiling and PED to assess the cost-effectiveness of these strategies.
Dual responsive neurostimulation implants for epilepsy
Authors: Barbaro Michael F. , Chesney Kelsi , Kramer Daniel R. , Kellis Spencer , Peng Terrance , Blumenfeld Zack , Gogia Angad S. , Lee Morgan B. , Greenwood Janet , Nune George , Kalayjian Laura A. , Heck Christianne N. , Liu Charles Y. , Lee Brian 
Published: February 2019

Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.
Management and outcomes of isolated interhemispheric subdural hematomas associated with falx syndrome
Authors: Tonetti Daniel A. , Ares William J. , Okonkwo David O. , Gardner Paul A. 
Published: February 2019

OBJECTIVELarge interhemispheric subdural hematomas (iSDHs) causing falx syndrome are rare; therefore, a paucity of data exists regarding the outcomes of contemporary management of iSDH. There is a general consensus among neurosurgeons that large iSDHs with neurological deficits represent a particular treatment challenge with generally poor outcomes. Thus, radiological and clinical outcomes of surgical and nonsurgical management for iSDH bear further study, which is the aim of this report.METHODSA prospectively collected, single-institution trauma database was searched for patients with isolated traumatic iSDH causing falx syndrome in the period from January 2008 to January 2018. Information on demographic and radiological characteristics, serial neurological examinations, clinical and radiological outcomes, and posttreatment complications was collected and tallied. The authors subsequently dichotomized patients by management strategy to evaluate clinical outcome and 30-day survival.RESULTSTwenty-five patients (0.4% of those with intracranial injuries, 0.05% of those with trauma) with iSDH and falx syndrome represented the study cohort. The average age was 73.4 years, and most patients (23 [92%] of 25) were taking anticoagulants or antiplatelet medications. Six patients were managed nonoperatively, and 19 patients underwent craniotomy for iSDH evacuation; of the latter patients, 17 (89.5%) had improvement in or resolution of motor deficits postoperatively. There were no instances of venous infarction, reaccumulation, or infection after evacuation. In total, 9 (36%) of the 25 patients died within 30 days, including 6 (32%) of the 19 who had undergone craniotomy and 3 (50%) of the 6 who had been managed nonoperatively. Patients who died within 30 days were significantly more likely to experience in-hospital neurological deterioration prior to surgery (83% vs 15%, p = 0.0095) and to be comatose prior to surgery (100% vs 23%, p = 0.0031). The median modified Rankin Scale score of surgical patients who survived hospitalization (13 patients) was 1 at a mean follow-up of 22.1 months.CONCLUSIONSiSDHs associated with falx syndrome can be evacuated safely and effectively, and prompt surgical evacuation prior to neurological deterioration can improve outcomes. In this study, craniotomy for iSDH evacuation proved to be a low-risk strategy that was associated with generally good outcomes, though appropriately selected patients may fare well without evacuation.
Assessment of lipoprotein-associated phospholipase A2 level and its changes in the early stages as predictors of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage
Authors: Ding Chen-Yu , Cai Han-Pei , Ge Hong-Liang , Yu Liang-Hong , Lin Yuan-Xiang , Kang De-Zhi 
Published: February 2019

OBJECTIVEThe relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.METHODSThe authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.RESULTSForty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).CONCLUSIONSThe serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.