Systematic review of prognostic models in traumatic brain injury

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability world-wide. The ability to accurately predict patient outcome after TBI has an important role in clinical practice and research. Prognostic models are statistical models that combine two or more items of patient data to predict clinical outcome. They may improve predictions in TBI patients. Multiple prognostic models for TBI have accumulated for decades but none of them is widely used in clinical practice. The objective of this systematic review is to critically assess existing prognostic models for TBI METHODS: Studies that combine at least two variables to predict any outcome in patients with TBI were searched in PUBMED and EMBASE. Two reviewers independently examined titles, abstracts and assessed whether each met the pre-defined inclusion criteria. RESULTS: A total of 53 reports including 102 models were identified. Almost half (47%) were derived from adult patients. Three quarters of the models included less than 500 patients. Most of the models (93%) were from high income countries populations. Logistic regression was the most common analytical strategy to derived models (47%). In relation to the quality of the derivation models (n:66), only 15% reported less than 10% pf loss to follow-up, 68% did not justify the rationale to include the predictors, 11% conducted an external validation and only 19% of the logistic models presented the results in a clinically user-friendly way CONCLUSION: Prognostic models are frequently published but they are developed from small samples of patients, their methodological quality is poor and they are rarely validated on external populations. Furthermore, they are not clinically practical as they are not presented to physicians in a user-friendly way. Finally because only a few are developed using populations from low and middle income countries, where most of trauma occurs, the generalizability to these setting is limited

Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

<p>Abstract</p> <p>Background</p> <p>Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied.</p> <p>Methods</p> <p>In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses.</p> <p>Results</p> <p>Under normoxic conditions, a half maximal inhibitory concentration (IC₅₀) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions.</p> <p>Conclusion</p> <p>Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.</p

The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

Human Mena Associates with Rac1 Small GTPase in Glioblastoma Cell Lines

Mammarian enabled (Mena), a member of the Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) family of proteins, has been implicated in cell motility through regulation of the actin cytoskeleton assembly, including lamellipodial protrusion. Rac1, a member of the Rho family GTPases, also plays a pivotal role in the formation of lamellipodia. Here we report that human Mena (hMena) colocalizes with Rac1 in lamellipodia, and using an unmixing assisted acceptor depletion fluorescence resonance energy transfer (u-adFRET) analysis that hMena associates with Rac1 in vivo in the glioblastoma cell line U251MG. Depletion of hMena by siRNA causes cells to be highly spread with the formation of lamellipodia. This cellular phenotype is canceled by introduction of a dominant negative form of Rac1. A Rac activity assay and FRET analysis showed that hMena knock-down cells increased the activation of Rac1 at the lamellipodia. These results suggest that hMena possesses properties which help to regulate the formation of lamellipodia through the modulation of the activity of Rac1

Tarifvertragliche Regulation - Erosion oder Gestaltungschancen?

'Ueber Jahrzehnte bestand weitgehender Konsens, dass eine wesentliche Basis des wirtschaftlichen Erfolgs der Bundesrepublik Deutschland auch in den positiven industriellen Beziehungen begruendet war. Die Tarifautonomie und der Flaechentarifvertrag sind dabei ein wesentliches Fundament. Dieser Konsens ist spaetestens in den neunziger Jahren bruechig geworden. Mehr und mehr wurde die branchenweite Regelung von Arbeitszeit und Einkommen in Frage gestellt und mehr Flexibilitaet fuer die Betriebe gefordert. Dies ist der Ausgangspunkt eines Forschungsprojekts, das von Prof.Dr. Lothar Peter und Reinhard Dietrich im Kooperationsbereich Universitaet Arbeitnehmerkammer (KUA) durchgefuehrt wird. Wie weit regeln Tarifvertraege noch die Standards in Betrieben? Welche Rolle spielen betriebliche Oeffnungsklauseln (Haertefallregelungen)? In welchem Ausmass entziehen sich Betriebe tarifvertraglichen Regelungen? Dies sind wesentliche Fragestellungen, die empirisch in Unternehmen der Unterweserregion untersucht werden. Die ersten Ergebnisse des noch bis 2002 laufenden Projekts wurden auf einer Tagung zur Diskussion gestellt, an der Akteure und Experten sowohl der Arbeitgeberseite wie auch der Gewerkschaften teilnahmen. Der Transfer solcher Forschungsergebnisse ist eine wichtige Aufgabe des Kooperationsbereichs Universitaet Arbeitnehmerkammer. Durch fruehzeitige Praesentation und Diskussion von Forschungsergebnissen sollen zugleich Anregungen von Betroffenen und Akteuren, aber auch Ergebnisse anderer wissenschaftlicher Untersuchungen Beruecksichtigung finden. Die im folgenden praesentierten, zum Teil kontroversen Tagungsbeitraege vermitteln einen Ueberblick ueber die wesentlichen Argumenten, die fuer oder wider die Regelung betrieblicher Arbeitsbeziehungen durch Flaechentarifvertraege vorgebracht wurden. Auch wurde die Notwendigkeit seiner Reform und Weiterentwicklungsmoeglichkeiten thematisiert.' (Textauszug). Inhaltsverzeichnis: Reinhard Dietrich, Lothar Peter: Tarifvertragspraxis in der Metall- und Elektroindustrie der Unterweser-Region als sozialer Prozess (6-21); Reinhard Bispinck: Betriebliche Interessenvertretung und Tarifpolitik in der Metallindustrie aus Sicht der Betriebsraete - Ergebnisse der WSI-Betriebsraetebefragung 1999/2000 (22-42); Helge Martin Krollmann: Die Regulierung der Arbeits- und Entlohnungsbedingungen ohne Tarifvertrag - eine realistische Perspektive? (43-48); Frank Teichmueller: Ergaenzungstarifvertraege stuetzen Flaechentarifvertraege (49-63); Martin Johannsmann, Claudia Reihert: Vertrauen ist die Basis von allem - Gestaltungsmoeglichkeiten zwischen Anerkennungstarifvertrag und Co-Management (64-70); Holger Pflaumbaum: Vom Sanierungstarifvertrag, ueber Ergaenzungstarifvertraege zum Flaechentarifvertrag. Ein Beitrag zum Erhalt des Schiffsneubaus in Bremerhaven (71-77); Hartmut Schulz: Gedanken zum Zustand und zur Entwicklung des Tarifsystems (78-87)SIGLEAvailable from UuStB Koeln(38)-20020107726 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman