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1.
Fabian Falkenstein Marco Gessi Daniela Kandels Ho-Keung Ng René Schmidt Monika Warmuth-Metz Brigitte Bison Juergen Krauss Rolf-Dieter Kortmann Beate Timmermann Ulrich-Wilhelm Thomale Michael H. Albert Arnulf Pekrun Eberhard Maaß Astrid K. Gnekow Torsten Pietsch 《International journal of cancer. Journal international du cancer》2020,147(8):2159-2175
Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment. 相似文献
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Licia Iaccarino Tiziana Ottone Valentina Alfonso Laura Cicconi Mariadomenica Divona Serena Lavorgna Serena Travaglini Aleandra Ferrantini Giulia Falconi Constance Baer Monica Usai Fabio Forghieri Adriano Venditti Maria Ilaria Del Principe William Arcese Maria Teresa Voso Torsten Haferlach Francesco Lo-Coco 《American journal of hematology》2019,94(10):1091-1097
Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile. 相似文献
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Ueberschaer M. Patzig M. Mueller K. Schwarting J. Trabold R. Tonn J.-C. 《Journal of neurology》2020,267(11):3421-3424
Journal of Neurology - A 50-year-old patient was admitted with symptoms of intracranial hypotension. MRI revealed a cervical myelomalacia caused by engorged epidural veins leading to a stenosis of... 相似文献
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Albert C. Ludolph MD Johannes Dorst MD Jens Dreyhaupt PhD Jochen H. Weishaupt MD Jan Kassubek MD Ulrike Weiland MD Thomas Meyer MD Susanne Petri MD Andreas Hermann MD PhD Alexander Emmer MD Julian Grosskreutz MD Torsten Grehl MD Daniel Zeller MD Matthias Boentert MD Bertold Schrank MD Johannes Prudlo MD Andrea S. Winkler MD Stanislav Gorbulev PhD Francesco Roselli MD PhD Joachim Schuster PhD Luc Dupuis PhD for the LIPCAL-ALS Study Group 《Annals of neurology》2020,87(2):206-216
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Anne Beck Patricia Pelz Robert C. Lorenz Katrin Charlet Olga Geisel Andreas Heinz Torsten Wüstenberg Christian A. Müller 《European neuropsychopharmacology》2018,28(11):1206-1216
Increased functional brain response towards alcohol-associated stimuli is a neural hallmark of alcohol dependence and a promising target for pharmacotherapy. For the first time, we assessed the effects of individually titrated high-dose baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) patients in a randomized controlled trial (RCT).We investigated 23 recently detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity functional magnetic resonance imaging task. Patients were further scanned at baseline without medication and during treatment with high-dose baclofen/placebo (30–270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, alcohol cue-modulated and stimulus-independent functional connectivity with left ventral tegmental area (VTA) as seed region.At baseline, AD patients (N?=?23) showed increased cue-elicited brain activation in the ventral striatum (VS) compared to HC (N?=?23), which was decreased at the second scanning session compared to baseline. Patients receiving baclofen (N?=?10) showed a significant stronger decrease in cue-elicited brain activation in left orbitofrontal cortex (OFC), bilateral amygdala and left VTA than patients receiving placebo (N?=?13). Treatment with baclofen further led to a decrease in alcohol cue-modulated functional connectivity between left VTA and left anterior cingulate cortex (ACC) as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, significantly more patients of the baclofen group remained abstinent during the high-dose period.Baclofen specifically decreased cue-elicited brain responses in areas known to be involved in the processing of salient (appetitive and aversive) stimuli. Treatment with high-dose baclofen seems to provide a pharmacological relief of this neural “warning signal” evoked by alcohol-related cues, thereby possibly supporting patients in remaining abstinent.Trial Registration Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655. 相似文献
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Mlanie Pags Kristian W. Pajtler Stphanie Puget David Castel Nathalie Boddaert Arnault Tauzide‐Espariat Stphanie Picot Marie‐Anne Debily Marcel Kool David Capper Christian Sainte‐Rose Fabrice Chrtien Stefan M. Pfister Torsten Pietsch Jacques Grill Pascale Varlet Felipe Andreiuolo 《Brain pathology (Zurich, Switzerland)》2019,29(3):325-335