bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia
Authors: Hijiya Nobuko , Thomson Blythe , Isakoff Michael S. , Silverman Lewis B. , Steinherz Peter G. , Borowitz Michael J. , Kadota Richard , Cooper Todd , Shen Violet , Dahl Gary , Thottassery Jaideep V. , Jeha Sima , Maloney Kelly , Paul Jo-Anne , Barry Elly , Carroll William L. , Gaynon Paul S. 
Published: October 2011

Abstract
The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.
Conditional Probability of Survival in Patients With Newly Diagnosed Glioblastoma
Authors: Polley Mei-Yin C. , Lamborn Kathleen R. , Chang Susan M. , Butowski Nicholas , Clarke Jennifer L. , Prados Michael 
Published: October 2011

Purpose The disease outcome for patients with cancer is typically described in terms of estimated survival from diagnosis. Conditional probability offers more relevant information regarding survival for patients once they have survived for some time. We report conditional survival probabilities on the basis of 498 patients with glioblastoma multiforme receiving radiation and chemotherapy. For 1-year survivors, we evaluated variables that may inform subsequent survival. Motivated by the trend in data, we also evaluated the assumption of constant hazard. Patients and Methods Patients enrolled onto seven phase II protocols between 1975 and 2007 were included. Conditional survival probabilities and 95% CIs were calculated. The Cox proportional hazards model was used to evaluate prognostic values of age, Karnofsky performance score (KPS), and prior progression 1-year post diagnosis. To assess the constant hazard assumption, we used a likelihood-ratio test to compare the Weibull and exponential distributions. Results The probabilities of surviving an additional year given survival to 1, 2, 3, and 4 years were 35%, 49%, 69%, and 93%, respectively. For patients who survived for 1 year, lower KPS and progression were significantly predictive of shorter survival (both P < .001), but age was not (hazard ratio, 1.22 for a 10-year increase; P = .25). The Weibull distribution fits the data significantly better than exponential (P = .02), suggesting nonconstant hazard. Conclusion Conditional probabilities provide encouraging information regarding life expectancy to survivors of glioblastoma multiforme. Our data also showed that the constant hazard assumption may be violated in modern brain tumor trials. For single-arm trials, we advise using individual patient data from historical data sets for efficacy comparisons.
Alternative End Points to Evaluate a Therapeutic Strategy in Advanced Colorectal Cancer: Evaluation of Progression-Free Survival, Duration of Disease Control, and Time to Failure of Strategy—An Aide et Recherche en Cancérologie Digestive Group Study
Authors: Chibaudel Benoist , Bonnetain Franck , Shi Qian , Buyse Marc , Tournigand Christophe , Sargent Daniel J. , Allegra Carmen J. , Goldberg Richard M. , de Gramont Aimery 
Published: October 2011

Purpose Progression-free survival (PFS) is not an optimal end point to evaluate therapeutic strategies in advanced colorectal cancer (ACRC). Therefore, composite end points have been proposed to evaluate a chemotherapy strategy when sequential treatments are available: duration of disease control (DDC) and time to failure of strategy (TFS). The goal of this study was to evaluate these alternative end points and their potential surrogacy for overall survival (OS). Methods We pooled individual patient data from three randomized trials evaluating chemotherapy strategy, which accrued 1,042 patients with previously untreated ACRC. In these trials, first-line treatment was either oxaliplatin- or irinotecan-based chemotherapy. Compared with TFS, DDC included neither time interval between progression and next sequence of treatment nor time to progression if the best result of the next sequence of treatment was progression. Results There was good correlation between DDC and OS (correlation of median: r, 0.62; correlation of hazard ratio [HR]: adjusted copula R2, 0.72) and between TFS and OS (correlation of median: r, 0.59; correlation of HR: adjusted copula R2, 0.67). There was no correlation between PFS and OS (correlation of median: r, 0.45; correlation of HR: adjusted copula R2, 0.47). Conclusion DDC and TFS roughly achieved the same results. Both are acceptable new end points to evaluate a therapeutic strategy in ACRC. Although TFS achieved a pragmatic evaluation of a multiline strategy, DDC captured the effect of a specific sequence in a therapeutic strategy.
Controlling the Lungs Via the Brain: A Novel Neurosurgical Method to Improve Lung Function in Humans
Authors: Hyam Jonathan A. , Brittain John-Stuart , Paterson David J. , Davies Robert J. O. , Aziz Tipu Z. , Green Alexander L. 
Published: October 2011

Abstract

BACKGROUND:
Deep brain stimulation (DBS) of subcortical brain areas such as the periaqueductal grey and subthalamic nucleus has been shown to alter cardiovascular autonomic performance. The supramedullary circuitry controlling respiratory airways is not well defined and has not been tested in humans.

OBJECTIVE:
To use direct electric stimulation via DBS macroelectrodes to test whether airway resistance could be manipulated by these areas in awake humans.

METHODS:
Thirty-seven patients with in-dwelling deep brain electrodes for movement disorders or chronic pain underwent spirometry according to the European Respiratory Society guidelines. Testing was performed randomly 3 times on stimulation and 3 times off stimulation; patients were blinded to the test. Thoracic diameter changes were measured by a circumferential pressure-sensitive thoracic band. Ten periaqueductal grey and 10 subthalamic nucleus patients were tested. To control for confounding pain and movement disorder relief, the sensory thalamus in 7 patients and globus pallidus interna in 10 patients, respectively, were also tested.

RESULTS:
Peak expiratory flow rate (PEFR) increased significantly with periaqueductal grey and subthalamic nucleus stimulation by up to 14% (P = .02 and .005, respectively, paired-samples Student t tests). Stimulation of control nuclei produced no significant PEFR change. Similarly, changes in thoracic diameter reflecting skeletal activity rather than airway caliber did not correlate with the improvement in PEFR. Forced expiratory volume in 1 second was unchanged by stimulation.

CONCLUSION:
DBS can improve PEFR in chronic pain and movement disorder patients. This finding provides insights into the neural modulation of respiratory performance and may explain some of the subjective benefits of DBS.
A Novel Scoring System for Assessing Chiari Malformation Type I Treatment Outcomes
Authors: Aliaga Leonardo , Hekman Katherine E. , Yassari Reza , Straus David , Luther Gaurav , Chen Judy , Sampat Ajay , Frim David 
Published: October 2011

Abstract

Background:
Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.

Objective:
We developed a novel scoring system and applied it retrospectively to 146 patients treated at our institution in order to create and verify a simple and quantifiable assessment of Chiari outcomes.

Methods:
The Chicago Chiari Outcome Scale (CCOS) uses 4 postoperative outcome categories (pain, nonpain symptoms, functionality, and complications) graded 1 to 4 for a total possible score of 16. As a comparison with current Chiari outcome methodology, each patient was also placed into a gestalt outcome group of “improved,” “unchanged,” or “worse” (I/U/W). Patients were stratified by CCOS scores and by I/U/W group.

Results:
Stratifying patients by total CCOS scores showed that patients who achieved CCOS scores between 13 and 16 were predominantly in the I/U/W improved group (n = 101, 69%); scores between 9 and 12 were predominantly I/U/W unchanged (n = 39, 27%), and scores between 4 and 8 were I/U/W worse (n = 6, 4%). Symptom subscore results provided insight into the specifics of the overall outcome in addition to the more quantitative nature of the 16-point scale.

Conclusion:
We describe a CCOS that assigns higher scores to patients judged improved by gestalt I/U/W ratings and lower scores to those who were unchanged or worse while defining outcome in 4 specific subcategories. As such, this CCOS should allow for a more unified and quantifiable outcome assessment after Chiari surgery.
Deep Brain Stimulation in Area LC Controllably Triggers Auditory Phantom Percepts
Authors: Larson Paul S. , Cheung Steven W. 
Published: October 2011

AbstractBACKGROUND:Tinnitus is predominantly viewed as the consequence of dysfunctional hyperactivity, plastic change, or synchronized oscillations in the central auditory system. An alternative to the current auditory-centric view of auditory phantom perception is the basal ganglia-centric view. Recent electrical stimulation experiments in area LC, a locus of the caudate nucleus positioned at its anterior body, has shown loudness modulation of existing tinnitus percepts.OBJECTIVE:To demonstrate that auditory phantoms are gated by the dorsal striatum.METHODS:Electrical stimulation in area LC via a deep brain stimulation lead was performed in 6 interactive adult subjects (3 with and 3 without chronic tinnitus) undergoing surgery to treat movement disorders. Tinnitus loudness was rated on a 0 to 10 scale, sound quality was described, and localization was referenced to 1 or both ears.RESULTS:Short-term area LC stimulation triggered new phantom tones, clicks, and frequency modulated sounds in 5 subjects and altered sound quality of an existing tinnitus percept in 1 subject. The results of this study indicate that perceptual awareness of auditory phantoms is contingent on satisfying a permission condition controlled by the dorsal striatum. Potential auditory phantoms are not automatically gated to reach perceptual awareness. A phantom percept gate control model is proposed.CONCLUSION:Neuromodulation of area LC can trigger temporary gate dysfunction and reversibly release new phantoms for conscious awareness. Restoration of restrictive dorsal striatal gate function to treat problematic phantom percepts may be realized by adopting long-term area LC neuromodulation and choosing optimal stimulation parameters.
The Incidence of Adjacent Segment Disease Requiring Surgery After Anterior Cervical Diskectomy and Fusion: Estimation Using an 11-Year Comprehensive Nationwide Database in Taiwan
Authors: Wu Jau-Ching , Liu Laura , Huang Wen-Cheng , Chen Yu-Chun , Ko Chin-Chu , Wu Ching-Lan , Chen Tzeng-Ji , Cheng Henrich , Su Tung-Ping 
Published: October 2011

Abstract

Background:
The incidence of symptomatic adjacent segment disease (ASD) after anterior cervical diskectomy and fusion (ACDF) was reported as 2.9%/y in a previous cohort of 374 patients. Few other data corroborate the incidence and natural history of ASD.

Objective:
To calculate the incidence of ASD after ACDF that required secondary fusion surgery.

Methods:
The retrospective study used an 11-year nationwide database to analyze the incidences. All patients who underwent ACDF for cervical disk diseases were identified through diagnostic and procedure codes. Kaplan-Meier and Cox regression analyses were performed.

Results:
From 1997 to 2007, covering 241 800 725.8 person-years, 19 385 patients received ACDF and 568 had ≥ 2 ACDF operations. The incidence of secondary ACDF operations was 7.6 per 1000 person-years. At the end of the 10-year cohort, 94.4% of patients who had received 1 ACDF remained free from secondary ACDF. The average time interval between the first and second ACDF was 23.3 months. After adjustment for comorbidities and socioeconomic status, secondary ACDF operations were more likely performed on male patients (hazard ratio = 1.27; P = .008) 15 to 39 years of age (hazard ratio = 1.45; P = .009) and 40 to 59 years of age (hazard ratio = 1.41, P = .002, respectively).

Conclusion:
Repeat ACDF surgery for ASD cumulated steadily in an annual incidence of approximately 0.8%, much lower than the reported incidence of symptomatic ASD. However, at the end of this 10-year cohort, a considerable portion of patients (5.6%) received a second operation. Younger and male patients are more likely to receive such second operations.
Styloidogenic Jugular Venous Compression Syndrome: Diagnosis and Treatment: Case Report
Authors: Dashti Shervin R. , Nakaji Peter , Hu Yin C. , Frei Don F. , Abla Adib A. , Yao Tom , Fiorella David , Ogungbo B. 
Published: October 2011

Abstract

Background and Importance:
Intracranial venous hypertension is known to be associated with venous outflow obstruction. We discuss the diagnosis and treatment of mechanical venous outflow obstruction causing pseudotumor cerebri.

Clinical Presentation:
We report 2 patients presenting with central venous outflow obstruction secondary to osseous compression of the internal jugular veins at the craniocervical junction. The point of jugular compression was between the lateral tubercle of C1 and a prominent, posteriorly located styloid process. In both cases, catheter venography showed high-grade jugular stenosis at the level of C1 with an associated pressure gradient. The dominant jugular vein was decompressed after the styloid process was resected. Postoperative imaging confirmed resolution of the jugular stenosis and normalization of preoperative pressure gradients. In both cases, the symptoms of intracranial hypertension resolved.

Conclusion:
Intracranial venous hypertension may result from extrinsic osseous compression of the jugular veins at the skull base. Although rare, this phenomenon is important to recognize because primary stenting not only is ineffective but also may actually exacerbate the outflow obstruction. The osseous impingement of the dominant jugular vein can be relieved via a decompressive styloidectomy, and the clinical results can be excellent.
Gamma Knife Thalamotomy for Parkinson Disease and Essential Tremor: A Prospective Multicenter Study
Authors: Ohye Chihiro , Higuchi Yoshinori , Shibazaki Toru , Hashimoto Takao , Koyama Toru , Hirai Tatsuo , Matsuda Shinji , Serizawa Toru , Hori Tomokatsu , Hayashi Motohiro , Ochiai Taku , Samura Hirofumi , Yamashiro Katsumi 
Published: October 2011

Abstract

BACKGROUND:
No prospective study of gamma knife thalamotomy for intractable tremor has previously been reported.

Objective:
To clarify the safety and optimally effective conditions for performing unilateral gamma knife (GK) thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a systematic postirradiation 24-month follow-up study was conducted at 6 institutions. We present the results of this multicenter collaborative trial.

Methods:
In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13) were registered at 6 Japanese institutions. Following our selective thalamotomy procedure, the lateral part of the ventralis intermedius nucleus, 45% of the thalamic length from the anterior tip, was selected as the GK isocenter. A single 130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological examination, magnetic resonance imaging and/or computerized tomography, the unified Parkinson's disease rating scale (UPDRS), electromyography, medication change, and video observations.

Results:
Final clinical effects were favorable. Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts II and III). Thalamic lesion size fluctuated but converged to either an almost spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high-signal zone (10.9%). No permanent clinical complications were observed.

Conclusion:
GK thalamotomy is an alternative treatment for intractable tremors of PD as well as for ET. Less invasive intervention may be beneficial to patients.
Surgical vs Nonoperative Treatment of Hadley Type IIA Odontoid Fractures
Authors: Aldrian Silke , Erhart Jochen , Schuster Rupert , Wernhart Simon , Domaszewski Florian , Ostermann Roman , Widhalm Harald , Platzer Patrick 
Published: October 2011

Abstract

Background:
Type II odontoid fractures with additional chip fragments are rare in clinical practice, accounting for &lt; 10% of all odontoid fractures. Hadley et al were the first to describe these fractures as an individual subtype (IIA).

Objective:
To analyze the outcome of patients after surgical or nonoperative treatment of Hadley type IIA odontoid fractures.

Methods:
We analyzed the records of 46 patients at an average of 64 years of age at the time of injury. Twenty-five patients underwent surgical stabilization by anterior screw fixation and were entered into study group A; 21 patients were treated non-operatively by halo vest immobilization and included in study group B.

Results:
Thirty-seven patients (84%) returned to their preinjury activity level and were satisfied with their treatment. Using the Cervical Spine Outcomes Questionnaire to quantify the clinical outcome, we had an overall outcome score of 21.8. We did not find a significant difference in the overall clinical outcome between study groups. Bony fusion was achieved in 35 patients (80%). We had a nonunion rate of 13% after anterior screw fixation and a significantly higher rate of 30% after halo vest immobilization. Failure of reduction or fixation occurred in 12 patients (27%), with a significantly higher failure rate after halo vest immobilization.

Conclusion:
Hadley type IIA odontoid fractures are inherently unstable and impede proper realignment. These fractures have a significantly increased risk for secondary loss of reduction and bony nonunion, particularly after nonoperative management. Early surgery should be considered to avoid further complications.
Back Pain: A Real Target for Spinal Cord Stimulation?
Authors: Rigoard Philippe , Delmotte Alexandre , D'Houtaud Samuel , Misbert Lorraine , Diallo Bakari , Roy-Moreau Aline , Durand Sylvain , Royoux Solène , Giot Jean-Philippe , Bataille Benoit 
Published: October 2011

AbstractBackground:Failed back surgery syndrome represents one of the most frequent etiologies of chronic back pain and is a major public health issue. Neurostimulation has currently not been validated in the treatment of back pain because of technological limitations in implantable spinal cord stimulation (SCS) systems. New-generation leads using several columns of stimulation can generate longitudinal and/or transverse stimulation fields into the spinal cord.Objective:To investigate, through extensive stimulation testing, the capacity of multicolumn tripolar leads to achieve back territory paresthesia coverage in refractory failed back surgery syndrome patients.Methods:Eleven patients implanted with a 16-contact spinal cord stimulation lead (Specify 5-6-5, Medtronic Inc) were assessed with a systematic exploration of 43 selected stimulation configurations to generate bilateral back paresthesia in addition to leg territory coverage.Results:The tripolar lead successfully generated paresthesia in both bilateral back and leg territories in 9 patients (81.8%). Success rates of multicolumn stimulation patterns were significantly higher than for longitudinal configurations for lombodorsal paresthesia coverage. Six months after implantation, significant pain relief was obtained compared with preoperative evaluation for global pain (Visual Analog Scale, 2.25 vs 8.2 preoperatively; P &lt; .05), leg pain (Visual Analog Scale, 0.5 vs 7.6 preoperatively; P &lt; .05), and back pain (Visual Analog Scale, 1.5 vs 7.8 preoperatively; P &lt; .05).Conclusion:These results suggest that multicolumn leads can reliably generate back pain coverage and favor pain relief outcomes. This may lead physicians to reconsider new indications for spinal cord stimulation. Expanding neurostimulation perspectives to intractable back pain syndromes could become realistic in the near future.
Evaluation of apparent diffusion coefficient mappings in amnestic mild cognitive impairment using an image analysis software brain search
Authors: Zhang Bing , Zhang Jian-ge , Zhao Hui , Zhang Xin , Li Ming , Qian Lai , Wang Kun , Tian Chuan-shuai , Guo Wan-hua , Cao Qiu-yun , Zhou Zheng-yang , Yu Haiping , Li Chen , Xu Jun , Cao Wangsen , Zhu Bin , Xu Yun 
Published: October 2011

Background The apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can quantify alterations in water diffusivity resulting from microscopic structural changes from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Purpose To investigate the ADC value for aMCI and AD using Brain Search (BS) software based on anatomical volumes of interest (AVOI). Material and Methods In total, 174 aged people were screened, and 25 patients with AD, 26 patients with aMCI, and 18 normal controls (NCs) were recruited. DWI was performed at 1.5 T with a fluid-attenuated inversion recovery (FLAIR), and the independent ADC mapping was generated after imaging acquisition. Ninety regional parcellations were adopted in a Brain Search (BS) based on the automated anatomic labeling atlas. The gray scale intensities (water diffusivity) from the collected ADC mappings were analyzed with BS. The mean value of each anatomical brain region was compared among aMCI, AD, and NC. The statistically significant ( P < 0.05) group differences are displayed in color. Results During the pathological process of AD, the changes of water diffusivity appeared first in the left hippocampus, then gradually progressed to the bilateral sides and eventually displayed right lateralization. The ADC values from aMCI were obviously elevated compared to the values from the NC group in the left limbic cortex. Between the AD and NC groups, the significantly different brain areas included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and the Temporal and Frontal lobes. There was a negative correlation between the ADC values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ. Additionally, the ADC values were positively correlated with the scores from CDR, ADL, and ADAS-Cog. Conclusion The water diffusivity for aMCI and AD displays asymmetric anatomical lateralization. The water diffusivity alterations can be analyzed and visualized with our newly designed analytic imaging software, BS, which can be used as a good reference for examining and diagnosing aMCI and AD patients.