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11.
Valter Poltojainen Janette Kemppainen Nina Keinnen Michaela Bode JuhaMatti Isokangas Hanne Kuitunen Juha Nikkinen Eila Sonkajrvi Vesa Korhonen Timo Tuovinen Matti Jrvel Niko Huotari Lauri Raitamaa Janne Kananen Tommi Korhonen Sami Tetri Outi Kuittinen Vesa Kiviniemi 《Human brain mapping》2022,43(13):4030
Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREGBOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREGBOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREGBOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 105mm3) extended spatially beyond FLAIR lesions (median 0.62 × 105mm3) with differences in volumes (p = .0055). 相似文献
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Thorsten Zenz Markus Kreuz Maxi Fuge Wolfram Klapper Heike Horn Annette M. Staiger Doris Winter Hanne Helfrich Jennifer Huellein Martin‐Leo Hansmann Harald Stein Alfred Feller Peter M?ller Norbert Schmitz Lorenz Trümper Markus Loeffler Reiner Siebert Andreas Rosenwald German Ott Michael Pfreundschuh Stephan Stilgenbauer for the German High‐Grade Non‐Hodgkin Lymphoma Study Group 《International journal of cancer. Journal international du cancer》2017,141(7):1381-1388
TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed. 相似文献
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Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection 总被引:1,自引:0,他引:1
Pedersen-Bjergaard U Pramming S Heller SR Wallace TM Rasmussen AK Jørgensen HV Matthews DR Hougaard P Thorsteinsson B 《Diabetes/metabolism research and reviews》2004,20(6):479-486
BACKGROUND: Differences between studies in rates of severe hypoglycaemia in type 1 diabetic cohorts are common and poorly understood. The purpose of this study was to assess the frequency of severe hypoglycaemia in unselected patients treated in different secondary care centres and to evaluate the influence of risk markers, clinical setting and selection. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive adult patients with clinical type 1 diabetes who completed a detailed questionnaire on hypoglycaemia and related issues. Key variable was the self-reported rate of severe hypoglycaemia during the preceding year. RESULTS: The overall rate of severe hypoglycaemia in the preceding year was 1.3 episodes/patient-year and episodes were reported by 36.7% of subjects. The distribution was highly skewed with 5% of subjects accounting for 54% of all episodes. There were no significant differences between countries or centres. Reduced hypoglycaemia awareness, peripheral neuropathy and smoking were the only significant risk markers of severe hypoglycaemia in a stepwise multivariate analysis. In a subgroup selected to be similar to the Diabetes Control and Complications Trial (DCCT) cohort, the rate of severe hypoglycaemia was 0.35 episodes/patient-year and only retinopathy was a significant risk marker together with state of awareness. CONCLUSION: Severe hypoglycaemia remains a significant clinical problem in type 1 diabetes. The rate of severe hypoglycaemia and the influence of risk markers are very sensitive to selection and differences in rates between centres or studies seem to disappear after correction for differences in clinical characteristics. Smoking is a novel overall risk marker of severe hypoglycaemia. 相似文献