Background Ventriculitis, a dreaded complication of brain abscess, meningitis, and various neurosurgical procedures, has attracted limited attention in the medical literature. Methods Retrospective single-centre study. We screened medical files of all patients who had a brain imaging report including the word “ventriculitis” during years 2005-2019. Only patients with clinical, microbiological and imaging features of ventriculitis were included. Data were collected through a standardized questionnaire. Results Ninety-eight patients fulfilled inclusion criteria: 42 women and 56 men, median age 60 years [interquartile range 48-68]. Primary mechanism for ventriculitis was classified as follows: brain abscess (n=29, 29.6%), meningitis (n=27, 27.6%), intraventricular catheter-related (n=17, 17.3%), post-neurosurgery (n=13, 13.3%), and hematogenous (n=12, 12.2%). Main neuroimaging features were intraventricular pus (n=81, 82.7%), ependymal enhancement (n=70, 71.4%) and intraventricular loculations (n=15, 15.3%). Main pathogens were streptococci (n=44, 44.9%), Gram-negative bacilli (n=27, 27.6%), and staphylococci (n=15, 15.3%). In-hospital and one-year mortality rates were, respectively, 30.6% (n=30), and 38.8% (n=38). Neurological sequelae were reported in 34/55 (61.8%) survivors, including cognitive impairment (n=11), gait disturbances (n=9), paresis (n=7), behavior disorder (n=6), epilepsy (n=5). On multivariate analysis, age > 65 years, Glasgow Coma Scale score < 13 at initial presentation, status epilepticus, hydrocephalus and positive cerebrospinal fluid culture were associated with one-year mortality. We built a scoring system to stratify patients with ventriculitis into low-risk (12.5%), intermediate-risk (36.5%), and high-risk (71.4%) of death. Conclusion Ventriculitis is a severe complication of brain abscess, meningitis, or neurosurgery, with in-hospital mortality rate of 30%, and neurological sequelae in 60% of survivors.
In the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gainof-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS).
Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas.Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC).Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min−1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP).Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.
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