Subgaleal Effusion and Brain Midline Shift After Cranioplasty: A Retrospective Study Between Polyetheretherketone Cranioplasty and Titanium Cranioplasty After Decompressive Craniectomy

Cranioplasty with polyetheretherketone (PEEK) has recently shown better cerebral protection performance, improved brain function, and aesthetic contour compared with titanium mesh. However, whether patients undergoing PEEK cranioplasty tend to develop subgaleal effusions remains elusive. This retrospective study included patients who underwent cranioplasty with PEEK implants or titanium mesh after decompressive craniectomy between July 2017 and July 2020. Patient information, including general information, location, size of the defect, subgaleal depth, and brain midline shift was collected and statistically analyzed. There were 130 cases of cranioplasty, including 35 with PEEK implants and 95 with a titanium mesh. Patients who underwent cranioplasty with a PEEK implant had a higher subgaleal effusion rate than those who underwent cranioplasty with titanium mesh (85.71% vs. 53.68%, P < 0.001), while a midline shift >5 mm was more frequently observed in the PEEK group than in the titanium group (20% vs. 6.3%, P = 0.021). The PEEK material was the only factor associated with subgaleal effusion after cranioplasty (OR 5.589, P = 0.002). Logistic regression analysis further showed that age was a protective factor against midline shift in the PEEK cranioplasty group (OR 0.837, P = 0.029). Patients who underwent cranioplasty with PEEK implants were more likely to develop severe subgaleal effusion and significant brain midline shifts than those with titanium mesh implants

Clinical Characteristics of Hydrocephalus Following the Treatment of Pyogenic Ventriculitis Caused by Multi/Extensive Drug-Resistant Gram-Negative Bacilli, Acinetobacter Baumannii, and Klebsiella Pneumoniae

ObjectiveHydrocephalus is common after ventriculitis. This study explores hydrocephalus's clinical characteristics following pyogenic ventriculitis due to multidrug-resistant and extensively drug-resistant Acinetobacter baumannii and Klebsiella pneumoniae.Patients and MethodsWe retrospectively reviewed patients with post-neurosurgical pyogenic ventriculitis due to multidrug-resistant and extensively drug-resistant A. baumannii and K. pneumoniae in our department between January 2014 and June 2020. Once diagnosed, patients received intraventricular lavage followed by daily intraventricular administration of Colistin (polymyxin-E). The patient's clinical/radiographic findings were analyzed and evaluated 6 months after discharge.ResultsIn total, 48 cases were included in this study, and 25% were female. The median age was 45 (SD ± 15) years old. Median intraventricular Colistin administration to acquire sterile cerebrospinal fluid (CSF) was 20 days. Forty-one patients developed hydrocephalus; among them, 18 (43%) had multiloculated hydrocephalus (MLH), 23 (56%) had uni/non-loculated hydrocephalus (ULH/NLH), and 7 (17%) did not develop hydrocephalus. The patients with MLH had (15 days) delayed initiation of intraventricular irrigation (p < 0.022). They had (32 days) longer intraventricular Colistin (p < 0.003) and showed worse outcomes in terms of Glasgow outcome score (GOS) at 6 months follow-up than those without hydrocephalus. The mean score of the MLH group was 1.67 (SD1.23), and ULH/NLH was 2.61 (SD1.4) at p < 0.008.ConclusionMultiloculated hydrocephalus is common in patients receiving delayed intraventricular administration of Colistin and required a longer duration on intraventricular Colistin to treat the pyogenic ventriculitis caused by multidrug/extensive drug-resistant A. baumannii and K. pneumoniae. It is associated with worse clinical outcomes

Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to temozolomide in human glioblastoma

Abstract Background Chemoresistance of glioblastoma (GBM) is a feature of this devastating disease. This study is to determine the relationship between Hedgehog (HH)/Gli1 signaling pathway and chemoresistance to temozolomide (TMZ) in human GBM. Methods We analyzed Gli1 nuclear staining and O6-methylguanine DNA methyltransferase (MGMT) expression in 48 cases of primary GBM tissues by immunohistochemistry. Quantitative PCR, western blot, methylation-specific PCR, cell proliferation and apoptosis assay were used to investigate changes of MGMT expression and chemosensitivity to TMZ after manipulating HH/Gli1 signaling activity in A172 and U251 GBM cell lines. Chromatin immunoprecipitation assay was utilized to identify potential Gli1 potential binding sites in MGMT gene promoter region. We established GBM xenografts using U251 cells to assess whether inhibiting HH/Gli1 signaling activity restored chemosensitivity to TMZ. Results O6-Methylguanine DNA methyltransferase-positive GBM tissues had a significantly higher rate of Gli1 nuclear staining than MGMT-negative ones (67.7% vs. 32.3%, p = 0.0159). Activation of HH/Gli1 signaling by pcDNA3.1-Gli1 cell transfection in A172 cells led to increased MGMT expression and enhanced resistance to TMZ treatment. Inhibition of the HH/Gli1 signaling by cyclopamine in U251 cells resulted in decreased MGMT expression and increased sensitivity to TMZ treatment. Both ways altered MGMT levels without changing the MGMT promoter methylation. The potential binding site of Gli1 in the MGMT gene promoter region was located at – 411 to − 403 bp upstream the transcriptional start site. The in vivo study revealed a synergistic effect on tumor growth inhibition with the combined administration of cyclopamine and TMZ. Conclusions This study shows that HH/Gli1 signaling pathway regulates MGMT expression and chemoresistance to TMZ in human GBM independent from MGMT promoter methylation status, which offers a potential target to restore chemosensitivity to TMZ in a fraction of GBM with high MGMT expression