Citations

Background and Purpose— The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists). Methods— The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects’ CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects’ CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement. Results— Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively). Conclusions— In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00623350.

Object Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. Methods Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. Results The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9–416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). Conclusions This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

External groups requiring measures now include public and private payers, regulators, accreditors and others that certify performance levels for consumers, patients and payers. Although benefits have accrued from the growth in quality measurement, the recent explosion in the number of measures threatens to shift resources from improving quality to cover a plethora of quality-performance metrics that may have a limited impact on the things that patients and payers want and need (ie, better outcomes, better care, and lower per capita costs). Here we propose a policy that quality measurement should be: balanced to meet the need of end users to judge quality and cost performance and the need of providers to continuously improve the quality, outcomes and costs of their services; and parsimonious to measure quality, outcomes and costs with appropriate metrics that are selected based on end-user needs.

Purpose. To investigate EEG and SPECT in the surgical outcome of patients with normal MRI (nonlesional) and extratemporal lobe epilepsy. Methods. We retrospectively identified 41 consecutive patients with nonlesional extratemporal epilepsy who underwent epilepsy surgery between 1997 and 2007. The history, noninvasive diagnostic studies (scalp EEG, MRI, and SPECT) and intracranial EEG (iEEG) monitoring was reviewed. Scalp and iEEG ictal onset patterns were defined. The association of preoperative studies and postoperative seizure freedom was analyzed using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard. Results. Thirty-six of 41 patients had adequate information with a minimum of 1-year followup. Favorable surgical outcome was identified in 49% of patients at 1 year, and 35% at 4-year. On scalp EEG, an ictal onset pattern consisting of focal beta-frequency discharge (>13–125 Hz) was associated with favorable surgical outcome (P=0.02). Similarly, a focal fast-frequency oscillation (>13–125 Hz) on iEEG at ictal onset was associated with favorable outcome (P=0.03). Discussion. A focal fast-frequency discharge at ictal onset identifies nonlesional MRI, extratemporal epilepsy patients likely to have a favorable outcome after resective epilepsy surgery.

Abstract Inflammation is a driving factor in the pathogenesis of many cancers including multiple myeloma. Myeloma is a plasma cell tumor whose early stages are characterized by cytokine dependent growth, predominantly driven by IL-6. We have demonstrated that IL-1β is a key inducer of IL-6 expressed by bone marrow stromal cells in a paracrine fashion. The P2X7 receptor (P2X7R) is an ATP-gated ion channel expressed by cells of the hematopoetic lineage that has been shown to play a critical role in IL-1β processing and secretion. We investigated the role this receptor may play in the IL-1/IL-6 cytokine pathway in multiple myeloma. A panel of multiple myeloma cell lines was evaluated by RT-PCR for the expression of P2X7R mRNA. Levels of expression in ANBL-6, MM1S, U266, RPMI-8226 and KAS-6/1 were comparable to U937, a previously characterized P2X7R positive cell line. A newly derived plasmacytoma cell line, PCYT3, showed very low levels of message expression. The ability of ATP to trigger the processing and release of IL-1β by activation of the P2X7 channel was studied using KAS-Pro, a myeloma cell line stably transfected with a pro- IL-1β gene. IL-1β, measured by ELISA, was released in a dose dependent fashion in response to increasing amounts of ATP ranging from 1mM to 5mM. Three P2X7R specific antagonists were tested for their effect on ATP stimulated IL- 1β release from KAS-Pro; all 3 compounds demonstrated inhibition in a dose dependent manner with varying degrees of potency correlating with P2X7R inhibition. In addition fresh patient samples (15 multiple myelomas/ 4 smoldering myelomas/8 MGUS) were evaluated for inhibition of IL-1β release by the P2X7R antagonists through direct measurement of IL-1β by ELISA as well as by an indirect measurement of IL-1β induced IL-6 production by normal bone marrow stromal cells. Greater than 90% inhibition of IL-1β release was demonstrated in all MM & SMM patients positive for IL-1β expression. IL-1β was not detected in any of the MGUS patients and therefore no affect of the inhibitors was observed. These results confirm the activity of functional P2X7 receptors on myeloma cell lines and in fresh patient samples and suggest a role for the use of P2X7 receptor antagonists in the therapy of myeloma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2582. doi:10.1158/1538-7445.AM2011-2582

Background — The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results — Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II, ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and diastolic (τ) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (* P <0.05 versus controls: 139±4* versus 123±4 mm Hg), week 5 (174±7* versus 124±4 mm Hg), and week 12 (181±12* versus 124±4 mm Hg). LV mass index was increased in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees was preserved in HTN-5wk and HTN-12wk. τ was increased in HTN-5wk (50±3* ms) and HTN-12wk (62±10* ms) dogs compared with sham (41±2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different from controls. Conclusions — Systemic HTN induces LV hypertrophy, myocardial fibrosis, and isolated diastolic dysfunction in the absence of local or systemic activation of Ang II or ET. These findings suggest that load is the prevailing stimulus for the structural and functional changes associated with early hypertensive heart disease.