Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients. Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I 2 = 0%; PPS: HR = 0.70, 95% CI 0.57–0.88, p < 0.01, I 2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47–3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82–1.10, p = 0.51, I 2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies. Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.

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PurposeThe aim of this study was to assess the neuroprotective effect of progesterone administration on severe traumatic brain injury (TBI) for different follow-up periods and administration route by completing a meta-analysis of randomized clinical trials (RCTs).MethodsA systematic literature search of PubMed, Embase, and Cochrane databases and the Web of Science (from establishment of each to September 1, 2018) was performed to identify original RCTs that evaluated the associations between progesterone treatment and the prognosis of patients with severe TBI.ResultsEight RCTs enrolling 2,251 patients with severe TBI were included. Within 3 months post-injury, patients with progesterone administration had a lower mortality (risk ratio [RR] =0.59; 95% CI [0.42–0.81], P=0.001) and better neurologic outcomes (RR =1.51; 95% CI [1.12–2.02], P=0.007) than those who received placebo. However, these differences did not persist at 6 months post-injury for mortality (RR =0.96; 95% CI [0.65–1.41], P=0.83) or neurologic outcomes (RR =1.09; 95% CI [0.93–1.27], P=0.31). The analysis stratified by administration route showed that beneficial effects were only observed in patients who received progesterone intramuscularly (RR =1.61, 95% CI [1.19–2.18], P=0.002); no benefit was observed with intravenous administration (RR =0.99, 95% CI [0.91–1.07], P=0.75).ConclusionProgesterone administration improved the clinical outcomes of severe TBI patients within 3 months but may not have significant long-term benefits 6 months post-injury.

PurposeCrohn's disease (CD) has been known to cause both abdominal pain alongside functional and structural alterations in the central nervous system (CNS) in affected patients. This study seeks to determine the alternations of metabolites in the bilateral anterior cingulate cortex (ACC) of CD patients with abdominal pain by using proton magnetic resonance spectroscopy (1H-MRS) to further explore the neural mechanism.MethodsSixteen CD patients with abdominal pain and 13 CD patients without abdominal pain, were recruited alongside 20 healthy controls (HCs) for this study. Clinical evaluations, including the 0–10 Visual Analogue Scale (VAS) of pain, Hospital Anxiety and Depression Scale (HADS) and Crohn's Disease Activity Index (CDAI), were evaluated prior to MR scanning. This study selected the bilateral ACC as the region of interest (ROI). The metabolites of the bilateral ACC were quantitatively analyzed by LCModel and Gannet. A independent sample t-test and one-way analysis of variance (ANOVA) were performed for statistical analysis. Spearman correlation analyses were performed to examine the relationship between the metabolite levels and clinical evaluations.ResultsThe results indicated that CD patients with abdominal pain exhibited significantly higher levels of Glutamate (Glu)/(creatine + phosphocreatine, total creatine, tCr) over CD patients without abdominal pain, and HCs (p = 0.003, 0.009, respectively) in the bilateral ACC. The level of (Glutamate + Glutamine, Glx)/tCr of pain CD group was higher than non-pain CD group (p = 0.022). Moreover, within the pain CD group, Glu/tCr and Glx/tCr levels correlated strongly with the VAS scores of pain (ρ = 0.86, 0.59 respectively, p < 0.05). Meanwhile, the results indicates that CD patients with abdominal pain have significantly lower levels of γ-aminobutyric acid plus (GABA+)/tCr (p = 0.002) than HCs. To some extent, CDAI demonstrated a trend of negative correlation with GABA+/tCr levels (p = 0.088, ρ = −0.60).ConclusionThe neural mechanism of CD patients with abdominal pain in pain processing is tightly associated with neurochemical metabolites. An imbalance in Glu and GABA may play a key role in abdominal pain processing for patients with CD. This mechanism of pain may associate with the intestinal microbiota on the brain-gut axis.

BACKGROUND:The debate about the efficacy of corticosteroids in the treatment of severe community-acquired pneumonia (CAP) is still a longstanding dilemma. We performed a meta-analysis including 4 randomized controlled trials (RCTs) to evaluate the effect of corticosteroids on the treatment of severe CAP in adults. METHODS: We performed a systematic review of published and unpublished clinical trials. Databases, including PubMed, Embase, CINAHL, and Cochrane (from their establishment to July 2013), were searched for relevant articles. Only RCTs of corticosteroids as adjunctive therapy in adult patients with severe CAP were selected. RESULTS: Four trials enrolling 264 patients with severe CAP were included. Use of corticosteroids significantly reduced hospital mortality compared with conventional therapy and placebo (Peto odds ratio ‫؍‬ 0.39, 95% CI 0.17-0.90). The quality of the evidence underlying the pooled estimate of effect on hospital mortality was low, downgraded for inconsistency and imprecision. CONCLUSIONS: On the basis of the current limited evidence, we suggest that, although corticosteroid therapy may reduce mortality and improve the prognosis of adult patients with severe CAP, the results should be interpreted with caution due to the instability of pooled estimates. Reliable treatment recommendations will be raised only when large sufficiently powered multi-center RCTs are conducted.