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Background— The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. Methods and Results— A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). Conclusions— The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigated.

Ziel: Multizentrischer Vergleich von manuellen ein-/bi-dimensionalen Messungen und semi-automatischen ein-/bi-dimensionalen und volumetrischen Messungen zur Beurteilung des Therapieansprechens beim Malignen Lymphopm in CT-Verlaufskontrollen. Material und Methoden: MSCT-Datensätze von Patienten mit Malignem Lymphom wurden vor (baseline) und nach zwei Zyklen Chemotherapie (follow-up) in fünf Universitätsradiologien ausgewertet. Der Langachsen- (LAD), der Kurzachsendurchmesser (SAD) und die bi-dimensionale WHO-Fläche von 307 Target-Lymphknoten wurden manuell und semi-automatisch unter Verwendung einer dedizierten Software bestimmt. Die Lymphknotenvolumetrie wurde lediglich semi-automatisch bestimmt. Das Therapieansprechen wurde anhand Lymphom-adaptierter RECIST-Kriterien beurteilt. Ergebnisse: Auf der Basis des einzelnen Lymphknotens wiesen semi-automatisch bestimmte mehrdimensionale Parameter einen höheren Anteil in der korrekten Beurteilung des Therapieansprechens als die die manuell oder semi-automatisch bestimmten eindimensionalen Parameter auf. Fehlklassifikationen wurden um bis 9,6 % reduziert. Zusätzlich war im Vergleich zu den manuellen Messungen der Einfluss auf die Beurteilung des Therapieansprechens in den einzelnen Studienzentren bei Anwendung semi-automatischer Messungen geringer. Schlussfolgerung: Die semi-automatische Volumetrie und die bi-dimensionale WHO-Messung reduzieren die Anzahl von Fehlklassifikationen in der Beurteilung des Therapieansprechens bei Patienten mit Malignem Lymphom signifikant um 9,6 % in einem Multicenterumfeld im Vergleich zu linearen Parametern. Semi-automatische Software-Tools können dazu beitragen, Fehlklassifikationen manueller Messungen zu reduzieren und sollten daher insbesondere in klinischen Studien zukünftig aber auch in die klinische Routine implementiert werden. Kernaussagen: BL Semi-automatisches Volumen und bi-dimensionaler WHO-Messungen reduzieren die Anzahl von Fehlklassifikationen beim Therapieansprechen signifikant (p

BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845. FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [