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This study aimed to compare the effectiveness of different graft materials using induced membrane technique for reconstruction of mandibular segmental bone defects. New Zealand rabbits were used as the experimental animal. As first-stage surgical procedure, segmental bone defects were created at the lower border of the mandibula in all groups. Polymethylmethacrylate (PMMA) cement was inserted into the defects. After 6 weeks, PMMA cement was removed in all groups. In the Control group, defect areas were left empty. Defects were filled with autogenous graft in the Autograft group, xenograft in the Xenograft group, and a mixture of autogenous graft and xenograft in the Autograft + Xenograft group. Histopathological, stereological, and immunohistochemical analyses were performed. A total of 40 New Zealand rabbits were used. Rabbits were randomly divided into four subgroups as Control, Autograft, Xenograft and Autograft + Xenograft groups (n = 10). When the groups were compared in terms of newly formed bone tissue volumes, significant difference was found between the Control group and Autograft group, Xenograft group and Autograft + Xenograft group (p < 0.001, p < 0.001, p = 0.003). The results of immunohistochemical examination were consistent with this finding. Stereological and immunohistochemical results can be used as a justification to adopt the induced membrane technique on an experimental basis in humans when it comes to the reconstruction of small segmental mandibular defects., Competing Interests: Declaration of competing interest The authors declared that they have no conflict of interest in regard to this work., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma., Materials and Methods: All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery., Results: Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0-3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively., Conclusion: The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs)., Methods: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics., Results: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival., Conclusions: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Ruptured middle cerebral artery (MCA) aneurysms are one of the causes of subarachnoid (SAH) or intracerebral hemorrhage (ICH) but the factors associated with the bleeding type are unknown. The aim of the study was to analyze the association of the morphological variations of the Sylvian fissure (SF) and vascular parameters on occurrence of different bleeding patterns in patients with ruptured MCA aneurysms., Patients and Methods: The data of consecutive 202 patients with ruptured MCA aneurysm of two centers were included for analysis. Patients were divided into three groups: Group 1 with SAH, Group 2 with accompanying ICH and Group 3 with intrasylvian hemorrhage (ISH). The SF was divided into five types according to the previously described classification. Analyzed vascular parameters were aneurysm size, localization, presence of a daughter aneurysm, shape, and angulation of the aneurysm sac., Results: A total of 202 patients (141 female, 61 male, mean age 52.4 yr) were included in this study. 67 patients (33.2%) had a SAH, 122 (60.4%) an ICH and 13 (6.4%) presented with ISH. Statistical analysis showed a significant association of narrow and twisted SF types 4 and 5 (p < 0.001) and temporal angulation of the aneurysm (p = 0.030) for occurrence of ICH. All other vascular parameters showed no significant association for any kind of hemorrhage., Conclusion: Our results allow the conclusion that the complex SF types 4 and 5, as well as the temporal angulation of the aneurysm sac are associated with the occurrence of ICH in ruptured MCA aneurysms., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Since publication of the ISAT study, the majority of neurovascular centers adhere to "coil first" policy for patients with subarachnoid hemorrhage (SAH). However, final allocation in favor of coiling or clipping is based on anatomic features of ruptured intracranial aneurysms with respect to clinical characteristics of SAH. In this study, we analyzed the parameters relevant for treatment allocation of ruptured anterior communicating artery aneurysms (AComAA)., Patients and Methods: From our institutional SAH database, all cases with ruptured AComAA, which underwent diagnostic subtraction angiography (DSA) with subsequent treatment allocation, were included. The radiographic features of AComAA were collected from pre-treatment DSA. In addition, demographic, clinical and radiographic parameters of SAH were recorded. The variables selected through univariate analyses were subsequently evaluated using multivariate regression analysis., Results: Of 300 SAH patients in the final analysis, the majority of the cases underwent endovascular coiling (n = 221, 73.7%). The following aneurysm features were associated with treatment modality in the univariate analysis: maximal sack size (p = 0.034), perpendicular height (p = 0.007), aspect ratio (p < 0.001) and sack/neck-ratio (p = 0.001). Accordingly, the following cutoffs for these variables were defined upon the receiver operating characteristics curves: 5 mm for sack size, 6 mm for perpendicular height, 1.6 for aspect ratio and sack/neck-ratio. In the multivariate analysis, aspect ratio of 1.6 was the only independent predictor of treatment allocation (p = 0.005; aOR = 2.57; 95% CI 1.33-4.96), which remained significant (p = 0.003; aOR = 2.77; 95% CI 1.41-5.45) after adjusting for patients' age, WFNS & Fisher grades, as well as intracerebral hematoma volume., Conclusion: Although not-routinely assessed during initial allocation treatment, our retrospective analysis proved that aspect ratio is a reliable predictor of treatment allocation of ruptured AComAA. Except for large space-occupying ICH commonly obligating the microsurgical treatment, other clinical and radiographic characteristics of SAH do not seem to be of clinical relevance for the selection of treatment modality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Several parameters like extent of resection and MGMT promotor methylation in glioblastoma (GBM) are known to influence survival. Other elements like multifocality and proliferation indices are not commonly used. The aim of the present study was to analyze routinely and not routinely assessed prognostic markers for survival of patients suffering from GBM in a single center., Methods: Adult cases with GBM operated at our institution were included in this survey. The association of age, Karnofsky performance status (KPS), MGMT promotor methylation, Ki67 proliferation index, IDH1/2 mutational status, and multifocality on overall survival (OS) was analyzed in univariate and multivariate cox regression models., Results: We analyzed 565 patients with a mean age of 62.2 (18-84) years. Median OS was 12.5 months. MGMT promoter methylation and IDH 1/2 mutation were associated with significant better OS (P < 0.01). In 48 cases (8.5%), the tumor was localized in both hemispheres, which was associated with a significant worse OS than tumor infiltration of 1 hemisphere (P = 0.039). Mean Ki67 proliferation index increased to 18% when both hemispheres were infiltrated. Multivariate analysis for OS revealed IDH 1/2 wildtype (adjusted odds ratio [aOR] 4.3), higher age (aOR 4.2), unmethylated MGMT promotor (aOR 3.5), preoperative KPS score <70 (aOR 1.9), and multifocality (aOR 2.1) as independent parameters for worse survival., Conclusions: This study confirms well-known parameters like MGMT promoter methylation, IDH 1/2 mutational status, KPS, and age as independent prognostic factors for survival and reveals multifocality as further independent prognostic marker for survival. The dismal prognosis of multifocal involvement is associated with an increasing Ki67 proliferation index., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Intraoperative aneurysm rupture (IOAR) is a common complication during intracranial aneurysm (IA) surgery. In light of the paradigm shift regarding IA selected for clipping in the post-International Subarachnoid Aneurysm Trial (ISAT) era, we aimed to evaluate the risk factors and effects of IOAR in an institutional series of clipped ruptured IA (RIA) and unruptured IA (UIA)., Material and Methods: All IAs treated with microsurgical clipping at our institution between 2003 and 2016 were eligible for this study. Demographic, clinical, and radiographic factors were correlated with occurrence of IOAR in univariate and multivariate analyses. The effect on outcome was analyzed for RIA and UIA separately., Results: Nine hundred and three clipped IAs were included in the final analysis (538 UIA and 365 RIA). IOAR occurred in 163 cases (18.1%), mostly during clipping of RIA (37.5% vs. 4.8%) In multivariate analysis, ruptured status (adjusted odds ratio [aOR], 10.46; P < 0.001), sack size (aOR, 1.05 per mm increase; P = 0.038) and IA location in the anterior communicating artery (aOR, 2.31; P < 0.001) independently predicted IOAR. For RIA cases, IOAR was also independently predicted by rebleeding before therapy (aOR, 3.11; P = 0.033) and clinical severity of subarachnoid hemorrhage (aOR, 1.18 per WFNS grade increase; P = 0.049). IOAR independently predicted poor outcome (aOR, 1.83; P = 0.042) after RIA surgery. In turn, IOAR affected only the risk for cerebral infarct (OR, 3.75; P = 0.003) and incomplete IA occlusion (OR, 3.45; P = 0.003) for UIA cases, but not the outcome (P = 0.263)., Conclusions: IOAR was independently predicted by the ruptured status, location, and size of IA and by initial severity of aneurysmal bleeding and pretreatment rebleeding. The influence of IOAR differed between RIA and UIA cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Decompressive craniectomy (DC) may become a life-saving measure for patients with subarachnoid hemorrhage (SAH). However, the benefit of early DC has not been shown yet. We aimed at identifying the clinical value of DC timing., Methods: We retrospectively analyzed 245 patients with SAH who underwent DC between January 2003 and December 2015. The cohort was stratified into primary (at admission, n = 171) and secondary DC (n = 74). In addition, primary DC was subdivided into early (≤24 hours after ictus, n = 120) and delayed (n = 51)., Results: There was no difference between primary and secondary DC (65.5% and 74.3%, P = 0.1828) with regard to unfavorable outcome at 6 months after SAH (defined as modified Rankin scale >3). However, individuals with early primary DC presented with significantly better functional outcome than the remaining cohort (P = 0.014, odds ratio [OR] = 2.02) and even compared with the subgroup with delayed primary DC (P = 0.023, OR = 2.42). Among individuals with World Federation of Neurosurgical Societies Grade <5 at admission, the benefits of early DC were more impressive: lower rates of unfavorable outcome (P = 0.003, OR = 0.28), in-hospital mortality (P = 0.031, OR = 0.37), and cerebral infarctions (P = 0.028, OR = 0.38) on the follow-up computed tomography scans., Conclusions: Not the timing of DC indication (primary/secondary), but rather the actual time left between the ictus and DC is crucial for the functional improvement of patients with SAH requiring DC. Especially, individuals without the signs of severe early brain injury strongly benefit from early DC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Although most neurovascular centers currently have a coil first policy, the percentage of coiled versus clipped aneurysms, as well as treatment outcomes, varies strongly between these centers. This study evaluates the impact of an increase in clipping caseload on treatment outcome in a large single-center series., Methods: All consecutive patients who underwent microsurgical clipping of unruptured intracranial aneurysms between January 2003 and April 2014 in our department were analyzed retrospectively. According to the change of the chairman in the neurosurgical department (1 September 2008) with a subsequent increase in the clipping volume, the entire cohort was divided into 2 groups with equal time intervals (historic and current cohorts)., Results: There were 94 clipped unruptured intracranial aneurysms in the historic cohort and 252 in the current cohort. Unfavorable outcome at 6 months postoperatively (defined as modified Rankin Score >2) was observed in 8 cases (8.5%) in the historic cohort and 7 cases (2.8%) in the current cohort (P < 0.0001). The surgical mortality decreased from 3.2% to 0%. Cerebral infarction on postoperative computed tomography scan was observed in 25 cases (26.6%) in the historic cohort and 19 cases (7.5%) in the current cohort (P < 0.0001). Within the current cohort, there was a progressive improvement of surgical outcome over the time., Conclusions: The improvement of the surgical outcome after increasing the clipping caseload underlines the importance of sufficient surgical volume for maintenance of competitive treatment results., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Objective: The aim of this study was to analyze our clinical and neurological results of surgically treated patients suffering from cervical spondylodiscitis with focusing particularly on the surgical methods used and to review the literature., Patients and Methods: We present a series of 21 patients operated with cervical spondylodiscitis between 1998 and 2011. Basic demographic data, comorbidities, the radiological segments involved, the surgical strategy with special consideration of the material used and the clinical outcome were evaluated retrospectively., Results: The mean age of 6 female and 12 male patients was 65 years (range 28-89 years). The mean follow-up was 3.7 years ranging between 4 weeks and 9 years. The leading symptom was neurological deficits rather than pain. The segments C 5/6 (n=8) and C 6/7 (n=7) were most frequently involved. Different surgical methods depending on the location, anatomical and pathological condition and extension of the lesion were performed., Conclusion: In conclusion, cervical spondylodiscitis could effectively be treated in the presented patient cohort by surgical decompression, debridement and PMMA or bone graft implants followed by long term antibiotic therapy. The presented surgical reconstruction technique with PMMA might be a feasible alternative to the use of bone graft or cages. The promising clinical results warrant future prospective studies to further investigate this technique., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aim: The objective of the present study was to evaluate the protective effects of halofuginone against renal ischemia/reperfusion (I/R) injury., Materials and Methods: Male Wistar albino rats were unilaterally nephrectomized and the left renal pedicles were occluded for 45 min to induce ischemia and then reperfused for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with either halofuginone (100 μg/kg/day) or saline 30 min prior to ischemia and the dose was repeated in the late reperfusion groups. In the sham groups, rats underwent unilateral nephrectomy and were treated at similar time points. The animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and kidney samples were obtained., Results: I/R injury increased renal malondialdehyde levels, myeloperoxidase activity and reactive oxygen radical levels, and decreased the renal glutathione content. Halofuginone treatment was found to reduce oxidative I/R injury and improve renal function in the rat kidney, as evidenced by reduced generation of reactive oxygen species, depressed lipid peroxidation and myeloperoxidase activity, and increased glutathione levels., Conclusions: The present findings demonstrate the anti-inflammatory and antioxidant effects of halofuginone in renal I/R injury, supporting its potential use where renal I/R injury is inevitable., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)