bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients
Authors: Hukkelhoven Chantal W. P. M. , Steyerberg Ewout W. , Rampen Anneke J. J. , Farace Elana , Habbema J. Dik F. , Marshall Lawrence F. , Murray Gordon D. , Maas Andrew I. R. 
Published: May 2009

Object. Increasing age is associated with poorer outcome in patients with closed traumatic brain injury (TBI). It is uncertain whether critical age thresholds exist, however, and the strength of the association has yet to be investigated across large series. The authors studied the shape and strength of the relationship between age and outcome, that is, the 6-month mortality rate and unfavorable outcome based on the Glasgow Outcome Scale.
Methods. The shape of the association was examined in four prospective series with individual patient data (2664 cases). All patients had a closed TBI and were of adult age (96% < 65 years of age). The strength of the association was investigated in a metaanalysis of the aforementioned individual patient data (2664 cases) and aggregate data (2948 cases) from TBI studies published between 1980 and 2001 (total 5612 cases). Analyses were performed with univariable and multivariable logistic regression.
Proportions of mortality and unfavorable outcome increased with age: 21 and 39%, respectively, for patients younger than 35 years and 52 and 74%, respectively, for patients older than 55 years. The association between age and both mortality and unfavorable outcome was continuous and could be adequately described by a linear term and expressed even better statistically by a linear and a quadratic term. The use of age thresholds (best fitting threshold 39 years) in the analysis resulted in a considerable loss of information. The strength of the association, expressed as an odds ratio per 10 years of age, was 1.47 (95% confidence interval [CI] 1.34–1.63) for death and 1.49 (95% CI 1.43–1.56) for unfavorable outcome in univariable analyses, and 1.39 (95% CI 1.3–1.5) and 1.46 (95% CI 1.36–1.56), respectively, in multivariable analyses. Thus, the odds for a poor outcome increased by 40 to 50% per 10 years of age.
Conclusions. An older age is continuously associated with a worsening outcome after TBI; hence, it is disadvantageous to define the effect of age on outcome in a discrete manner when we aim to estimate prognosis or adjust for confounding variables.
Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness
Authors: Honegger Jürgen , Prettin Carsten , Feuerhake Friedrich , Petrick Manfred , Schulte-Mönting Jürgen , Reincke Martin 
Published: May 2009

Object. The cell cycle—dependent nuclear antigen Ki-67 is related to growth potential in a variety of tumors. Elevated expression of Ki-67 was previously shown in recurrent pituitary adenomas; however, it has remained unclear whether this expression is related to the growth velocity or invasive behavior of these tumors. The aim of this study was to determine the correlation of Ki-67 antigen expression, growth velocity, and invasiveness in nonfunctioning pituitary adenomas.
Methods. Between April 1998 and April 2002, 23 patients with nonfunctioning pituitary adenomas who had participated in an observation period in which multiple computerized tomography and magnetic resonance imaging studies had been performed were surgically treated in our department. Tumor volumes were assessed using a stereological method based on the Cavalieri principle. The growth rate was calculated for each patient. Expression of Ki-67 antigen was examined using the monoclonal antibody MIB-1.
The assessed growth velocity of the adenomas was best described by a linear growth model. The correlation between Ki-67 expression and growth rate was highly significant. Rapidly growing adenomas (>0.07% daily increase in size) were found to have a Ki-67 labeling index (LI) exceeding 1.5%, whereas all five adenomas with a very slow growth rate (< 0.02% daily increase in size) had a Ki-67 LI lower than 1.5%. No correlation was found between the growth rate and the invasive character of the adenomas.
Conclusions. Expression of Ki-67 antigen is significantly correlated to the growth velocity of pituitary adenomas. Invasive behavior is a feature independent of proliferative activity. The extent of Ki-67 expression is helpful for clinical decision making and routine assessment of Ki-67 is recommended during the histopathological workup of pituitary adenomas.
Management of vestibular schwannoma by fractionated stereotactic radiotherapy and associated cerebrospinal fluid malabsorption
Authors: Sawamura Yutaka , Shirato Hiroki , Sakamoto Touru , Aoyama Hidefumi , Suzuki Keishiro , Onimaru Rikiya , Isu Toyohiko , Fukuda Satoshi , Miyasaka Kazuo 
Published: May 2009

Object. The goal of this study was to investigate outcomes in patients with vestibular schwannoma (VS) who were treated with fractionated stereotactic radiotherapy (SRT).
Methods. One hundred one patients with VS were treated with fractionated SRT at a radiation level of 40 to 50 Gy administered in 20 to 25 fractions over a 5- to 6-week period. The median tumor size in these patients was 19 mm (range 3–40 mm), and 27 tumors were larger than 25 mm. Patients were consistently followed up using magnetic resonance imaging every 6 months for 5 years in principle. The median follow-up period was 45 months. The actuarial 5-year rate of tumor control (no growth > 2 mm and no requirement for salvage surgery) was 91.4% (95% confidence interval 85.2–97.6%). Three patients with progressive tumors underwent salvage tumor resection. The actuarial 5-year rate of useful hearing preservation (Gardner—Robertson Class I or II) was 71%. The observed complications of fractionated SRT included transient facial nerve palsy (4% of patients), trigeminal neuropathy (14% of patients), and balance disturbance (17% of patients). No new permanent facial weakness occurred after fractionated SRT. Eleven patients (11%) who had progressive communicating hydrocephalus (cerebrospinal fluid malabsorption) and no evidence of tumor growth after fractionated SRT required a shunt. The symptoms of this type of hydrocephalus were similar to those of normal-pressure hydrocephalus and occurred 4 to 20 months (median 12 months) after fractionated SRT. The mean size (± standard deviation) of tumors causing symptomatic hydrocephalus (25.5 ± 7.8 mm) was significantly larger than that of other tumors (18.2 ± 8.7 mm) (p = 0.011). Only four of the 72 patients with tumors smaller than 25 mm in maximum diameter received a shunt.
Conclusions. Fractionated SRT resulted in an excellent tumor control rate, even for relatively large tumors, and produced a high rate of hearing preservation that was comparable to the best results of single-fraction radiosurgery. The progression of communicating hydrocephalus should be monitored closely, particularly in patients harboring a large VS.
Fusobacterial brain abscess: a review of five cases and an analysis of possible pathogenesis
Authors: Han Xiang Y. , Weinberg Jeffrey S. , Prabhu Sujit S. , Hassenbusch Samuel J. , Fuller Gregory N. , Tarrand Jeffrey J. , Kontoyiannis Dimitrios P. 
Published: May 2009

Object. The cases of five patients with fusobacterial brain abscess are presented. The authors discuss their attempt to determine the pathogenesis.
Methods. The clinical and microbiological features of five cases of fusobacterial brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other anaerobes collected (1989–2002) at our institution were analyzed and compared for incidences and isolation sources. The findings were correlated with extensive literature on the subject.
The five patients were men between 45 and 74 years of age. All experienced an insidious onset of the disease and probable hematogenous seeding of the organism(s). One patient had a monomicrobic Fusobacterium necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses. Despite surgery and a regimen of antibiotic medications and dexamethasone, three patients experienced a paradoxical deterioration 3 days postoperatively that necessitated reevacuation of the lesion. The evacuants observed at that time contained numerous leukocytes but no microorganisms, suggesting intensified inflammation as the likely cause of deterioration. This explanation is supported by literature that fusobacteria strongly activate neutrophils. An analysis of the 2031 anaerobes from blood, wounds, and abscesses showed the considerable virulence of Fusobacterium spp., which were able to enter and/or sustain themselves in the blood circulation. This pattern was similar to that of Clostridium spp., but different from those of Peptostreptococcus spp., Bacteroides spp., and Prevotella spp., which were less invasive but more abundant.
Conclusions. Some fusobacterial brain abscesses may be associated with a paradoxical postoperative deterioration, which is probably due to intensified inflammation following treatment. The blood-borne dissemination and invasive behavior of fusobacteria likely initiate such a brain abscess, and further seeding of other synergic bacteria leads to a polymicrobic abscess.
Association between a black band on the inner membrane of a chronic subdural hematoma on T2*-weighted magnetic resonance images and enlargement of the hematoma
Authors: Imaizumi Toshio , Horita Yoshifumi , Honma Toshimi , Niwa Jun 
Published: May 2009

Object. The cause and indication for enlargement of chronic subdural hematomas (CSDHs) have remained unresolved. The authors observed a black band on the inner membrane of a CSDH on T2*-weighted magnetic resonance (MR) images obtained in patients with symptoms. After surgical treatment, the band disappeared. The T2*-weighted sequence of MR imaging is an excellent diagnostic tool for detecting ferromagnetic substances, but it is rarely performed in cases of a CSDH. The authors speculate that the black band may be associated with the development of CSDH.
Methods. To investigate how the black band observed on T2*-weighted MR images contributes to the development of a CSDH, 59 lesions in 50 patients with CSDH (41 men and nine women, mean age 70 ± 11 years [range 48–93 years]) were investigated prospectively. The incidence of black bands on the first T2*-weighted MR image obtained in patients with symptomatic CSDH was 97% (31 of 32 CSDHs), which was significantly higher than that associated with asymptomatic CSDH (11% [three of 27 CSDHs], p < 0.001). The black bands associated with symptomatic CSDH disappeared soon after surgical treatment in 31 CSDHs and became fainter in another. In two instances the CSDH recurred with reappearance of the band. Twenty-four of 27 asymptomatic CSDHs had no accompanying black band. Follow-up MR images demonstrated a later formation of bands in two of 24 asymptomatic CSDHs that enlarged to symptomatic size. Logistic regression analysis revealed that the heterogeneity and thickness of the CSDH on computerized tomography scans were independently and significantly associated with the black band.
Conclusions. The dynamics of the black band may depend on the enlargement or shrinkage of the CSDH.
Recurrent spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study
Authors: Schievink Wouter I. , Maya M. Marcel , Riedinger Mary 
Published: May 2009

Object. Intracranial hypotension due to a spontaneous spinal cerebrospinal fluid (CSF) leak is an increasingly recognized cause of postural headaches, but reliable follow-up data are lacking. The authors undertook a study to determine the risk of a recurrent spontaneous spinal CSF leak.
Methods. The patient population consisted of a consecutive group of 18 patients who had been evaluated for consideration of surgical repair of a spontaneous spinal CSF leak. The mean age of the 15 women and three men was 38 years (range 22–55 years). The mean duration of follow up was 36 months (range 6–132 months). The total follow-up time was 654 months. A recurrent spinal CSF leak was defined on the basis of computerized tomography myelography evidence of a CSF leak in a previously visualized but unaffected spinal location. Five patients (28%) developed a recurrent spinal CSF leak; the mean age of these four women and one man was 36 years. A recurrent CSF leak developed in five (38%) of 13 patients who had undergone surgical CSF leak repair, compared with none (0%) of five patients who had been treated non-surgically (p = 0.249). The recurrent leak occurred between 10 and 77 months after the initial CSF leak, but within 2 or 3 months of successful surgical repair of the leak in all patients.
Conclusions. Recurrent spontaneous spinal CSF leaks are not rare, and the recent successful repair of such a leak at another site may be an important risk factor.
Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a population-based study of 993 patients in whom tumors were diagnosed between 1970 and 1993
Authors: Johannesen Tom B. , Langmark Frøydis , Lote Knut 
Published: May 2009

Object. The goal of this study was to document and compare long-term survival during the periods 1970 through 1981 and 1982 through 1993 in all adult patients in Norway with histologically verified supratentorial low-grade gliomas (LGGs).
Methods. Nine hundred ninety-three patients 15 to 69 years of age were found to have a primary supratentorial diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, or pilocytic astrocytoma. Survival time was analyzed in all patients and, in a subset of 451 patients, the influence of new imaging methods on the time from symptom onset to imaging diagnosis was estimated.
Overall median survival was 6.4 years (95% confidence interval [CI] 5.7–7.1 years). Survival times for patients in whom a diagnosis was made between 1970 and 1981 (397 patients) and between 1982 and 1993 (596 patients) were 4.1 years (95% CI 3.3–4.9 years) and 9.2 years (95% CI 7.9–10.6 years), respectively (p < 0.0001). Survival also improved in the later period within each histological subgroup. In patients in whom a biopsy was performed the median length of survival was 6.4 years (95% CI 3.1–9.7 years); in patients treated with subtotal tumor resection it was 6.8 years (95% CI 5.8–7.7 years); and in those treated with gross-total tumor resection it was 7.6 years (95% CI 5.5–9.7 years), a nonsignificant difference (p = 0.59). A considerable age-dependent variation in overall survival was demonstrated. The availability of computerized tomography (CT) scanning and/or magnetic resonance (MR) imaging as a diagnostic tool reduced the median period of symptoms prior to diagnosis by 6 months.
Conclusions. Long-term overall survival significantly improved, but age-related differences in prognosis persisted. The increased sensitivity of the diagnostic method due to the availability of CT scanning and/or MR imaging may partly, but not entirely, account for the observed magnitude of improvement in overall survival. Thus local tumor treatment improved during the study period.
Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats
Authors: Degen Jeffrey W. , Walbridge Stuart , Vortmeyer Alexander O. , Oldfield Edward H. , Lonser Russell R. 
Published: May 2009

Object. Convection-enhanced delivery (CED) can be used safely to perfuse regions of the central nervous system (CNS) with therapeutic agents in a manner that bypasses the blood—brain barrier (BBB). These features make CED a potentially ideal method for the distribution of potent chemotherapeutic agents with certain pharmacokinetic properties to tumors of the CNS. To determine the safety and efficacy of the CED of two chemotherapeutic agents (with properties ideal for this method of delivery) into the CNS, the authors perfused naive rats and those harboring 9L gliomas with carboplatin or gemcitabine.
Methods. Dose-escalation toxicity studies were performed by perfusing the striatum (10 µl, 24 rats) and brainstem (10 µl, 16 rats) of naive rats with carboplatin (0.1, 1, and 10 mg/ml) or gemcitabine (0.4, 4, and 40 mg/ml) via CED. Efficacy trials involved the intracranial implantation of 9L tumor cells in 20 Fischer 344 rats. The tumor and surrounding regions were perfused with 40 µl of saline (control group, four rats), 1 mg/ml of carboplatin (four rats), or 4 mg/ml of gemcitabine (four rats) 7 days after implantation. Eight rats harboring the 9L glioma were treated with the systemic administration of 60 mg/kg of carboplatin (four rats) or 150 mg/kg of gemcitabine (four rats) 7 days postimplantation. Clinical, gross, and histological analyses were used to determine toxicity and efficacy.
Toxicity occurred in rats that had received only the highest dose of the CED of carboplatin or gemcitabine. Among rats with 9L gliomas, all control and systemically treated animals died within 26 days of tumor implantation. Long-term survival (120 days) and eradication of the tumor occurred in both CED-treated groups (75% of rats in the carboplatin group and 50% of rats in the gemcitabine group). Furthermore, animals harboring the 9L glioma and treated with intratumoral CED of carboplatin or gemcitabine survived significantly longer than controls treated with intratumoral saline (p < 0.01) or systemic chemotherapy (p < 0.01).
Conclusions. The perfusion of sensitive regions of the rat brain can be accomplished without toxicity by using therapeutic concentrations of carboplatin or gemcitabine. In addition, CED of carboplatin or gemcitabine to tumors in this glioma model is safe and has potent antitumor effects. These findings indicate that similar treatment paradigms may be useful in the treatment of glial neoplasms in humans.
Effects of delayed, prolonged hypothermia on the pial vascular response after traumatic brain injury in rats
Authors: Ueda Yuji , Wei Enoch P. , Kontos Hermes A. , Suehiro Eiichi , Povlishock John T. 
Published: May 2009

Object. In the experimental setting, hypothermia has been demonstrated to attenuate the damaging consequences of stroke and traumatic brain injury (TBI). Laboratory studies of TBI have focused primarily on the use of early hypothermic intervention, with little consideration of the potential efficacy of more delayed but prolonged hypothermia, which would constitute a more clinically relevant approach. In this investigation, the authors evaluated whether delayed, prolonged hypothermia after TBI protected the cerebral microcirculation.
Methods. Male Sprague—Dawley rats were equipped with cranial windows for direct visualization of the pial arterial circulation and then subjected to impact-acceleration brain injury. The rats were randomly divided into four experimental groups: Group 1 consisted of normothermic animals; in Group 2 the rats received a 1-hour period of hypothermia (32°C) 30 minutes posttrauma, followed by slow rewarming (32–37°C/90 minutes); and in Groups 3 and 4 the rats received a more delayed induction (at 1 hour postinjury) of either 1 hour (Group 3) or 2 hours (Group 4) of hypothermia, followed by the slow rewarming. The pial arteriolar responses to acetylcholine (ACh) or hypercapnia were measured until up to 6 hours postinjury. With this approach the authors found that the normothermic group demonstrated severely impaired vasoreactivity in terms of ACh-dependent dilation and CO2 reactivity in comparison to baseline values (p < 0.001). In contrast, hypothermia of short duration that was initiated early (30 minutes postinjury) conferred significant cerebrovascular protection (p < 0.001), yet this protection was reduced when the onset of this 1-hour hypothermic period was postponed to 1 hour postinjury. Nevertheless, reduced protection could be significantly improved (p < 0.001) with prolongation of the hypothermic period to 2 hours.
Conclusions. The results of this study show that early as well as delayed but prolonged hypothermia attenuate the impaired vascular responsiveness seen after TBI, indicating the potential clinical usefulness of this treatment.
Interleukin-1β and adverse effects on cerebral blood flow during long-term global hypoperfusion
Authors: Maher Cormac O. , Anderson Robert E. , Martin Heidi S. , McClelland Robyn L. , Meyer Fredric B. 
Published: May 2009

Object. The effects of interleukin (IL)-1β on the cerebral vasculature are complex and incompletely understood. Many pathophysiological states in which inflammatory cascades have been implicated also have varying degrees of cerebral hypoperfusion. The purpose of this investigation was to examine the long-term effects of this proinflammatory cytokine and its antagonist on cerebral blood flow (CBF) following global cerebral hypoperfusion.
Methods. Sprague—Dawley rats were randomly assigned to 12 groups and given continuous intracerebroventricular (ICV) infusions of IL-1β, the IL-1 receptor antagonist (IL-1ra), or saline vehicle (control). Global cerebral hypoperfusion was produced by occlusion of both carotid arteries and one vertebral artery. Cerebral blood flow was measured at baseline and again after initiation of the infusions by performing a 133Xe clearance study.
Prolonged ICV administration of IL-1β resulted in a significant decrease in CBF compared with that in controls. Prolonged administration of the antagonist IL-1ra resulted in significant increases in CBF compared with that in both IL-1β—treated animals and controls.
Conclusions. This experiment demonstrates that long-term treatment with the proinflammatory cytokine IL-1β adversely affects CBF.
No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled clinical trial
Authors: Siironen Jari , Juvela Seppo , Varis Joona , Porras Matti , Poussa Kristiina , Ilveskero Sorella , Hernesniemi Juha , Lassila Riitta 
Published: May 2009

Object. From the moment an intracranial aneurysm ruptures, cerebral blood flow is impaired, and this impairment mainly determines the outcome in patients who survive after the initial bleeding. The exact mechanism of impairment is unknown, but activation of coagulation and fibrinolysis correlate with clinical condition and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether enoxaparin, a low-molecular-weight heparin, which is a well-known anticoagulating agent, has any effect on the outcome of aneurysmal SAH postoperatively.
Methods. In this randomized, double-blind, single-center clinical trial, 170 patients (85 per group) with aneurysmal SAH were randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily) or a placebo, starting within 24 hours after occlusion of the aneurysm and continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales. Patients were eligible for the study if surgery was performed within 48 hours post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on the first postoperative computerized tomography scan.
At 3 months, there were no significant differences in outcome by treatment group. Of the 170 patients, 11 (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable outcome were poor initial condition, delayed cerebral ischemia, and surgical complications. There were four patients with additional intracranial bleeding in the group receiving enoxaparin. The bleeding was not necessarily associated with the treatment itself, nor did it require treatment, and there were no such patients in the placebo group.
Conclusions. Enoxaparin seemed to have no effect on the outcome of aneurysmal SAH in patients who had already received routine nimodipine and who had received triple-H therapy when needed. Routine use of low-molecular-weight heparin should be avoided during the early postoperative period in patients with SAH, because this agent seems to increase intracranial bleeding complications slightly, with no beneficial effect on neurological outcome.