ObjectiveThe prefabrication of customized cranioplastic implants has been introduced to overcome the difficulties of intra-operative implant molding. The authors present a new technique, which consists of the prefabrication of implant molds using three-dimensional (3D) printers and polymethyl-methacrylate (PMMA) casting.MethodsA total of 16 patients with large skull defects (>100 cm2) underwent cranioplasty between November 2009 and April 2011. For unilateral cranial defects, 3D images of the skull were obtained from preoperative axial 1-mm spiral computed tomography (CT) scans. The image of the implant was generated by a digital subtraction mirror-imaging process using the normal side of the cranium as a model. For bilateral cranial defects, precraniectomy routine spiral CT scan data were merged with postcraniectomy 3D CT images following a smoothing process. Prefabrication of the mold was performed by the 3D printer. Intraoperatively, the PMMA implant was created with the prefabricated mold, and fit into the cranial defect.ResultsThe median operation time was 184.36±26.07 minutes. Postoperative CT scans showed excellent restoration of the symmetrical contours and curvature of the cranium in all cases. The median follow-up period was 23 months (range, 14-28 months). Postoperative infection was developed in one case (6.2%) who had an open wound defect previously.ConclusionCustomized cranioplasty PMMA implants using 3D printer may be a useful technique for the reconstruction of various cranial defects.

Over the 8 months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was free of serious adverse events, and several patients showed mild improvements in neurological function. Patient selection, dosage, and delivery method of ADMSCs should be investigated further.

Irreversible and permanent damage develop immediately adjacent to the region of reduced cerebral blood perfusion in stroke patients. Currently, the proven thrombolytic treatment for stroke, tissue plasminogen activator, is only effective when administered within 3 h after stroke. These disease characteristics should be taken under consideration in developing any therapeutic intervention designed to widen the narrow therapeutic range, especially cell-based therapy. Over the past several years, our group and others have characterized the therapeutic potential of human umbilical cord blood cells for stroke and other neurological disorders using in vitro and vivo models focusing on the cells' ability to differentiate into nonhematopoietic cells including neural lineage, as well as their ability to produce several neurotrophic factors and modulate immune and inflammatory reaction. Rather than the conventional cell replacement mechanism, we advance alternative pathways of graft-mediated brain repair involving neurotrophic effects resulting from release of various growth factors that afford cell survival, angiogenesis, and anti-inflammation. Eventually, these multiple protective and restorative effects from umbilical cord blood cell grafts may be interdependent and act in harmony in promoting therapeutic benefits for stroke.

Objective : In this study, the Mindfulness Based Stress Reduction (MBSR) program was applied to patients presenting with depression and anxiety after surgery from spontaneous subarachnoid hemorrhage (SAH) and the effects were assessed. Methods : The subjects were patients admitted for cerebral aneurysm rupture and treated by means of surgery from March to December, 2007. More than 6 months had passed after surgery, without any special lesions showing up on computed tomography (CT), and the Glasgow outcome scale (GOS) was 5 points. Among patients with anxiety and depression symptoms, 11 patients completed the program. The MBSR program was conducted once a week, 2.5 hours each, for 8 weeks. The evaluation criteria were : 1) the Beck Depression Inventory (BDI): it measures the type and level of depression, 2) the State-Trait Anxiety Inventory : the anxiety state of normal adults without mental disorder, and 3) Heart Rate Variability (HRV) : the influence of the autonomous nervous system on the sinoarterial node varies continuously in response to the change of the internal/external environment. Results : The BDI value was decreased from 18.5 ± 10.9 to 9.5 ± 7.1 (p = 0.013) : it was statistically significant, and the depression level of patients was lowered. The state anxiety was decreased from 51.3 ± 13.9 to 42.3 ± 15.2; the trait anxiety was reduced from 50.9 ± 12.3 to 41.3 ± 12.8, and a borderline significant difference was shown (p = 0.091, p = 0.056). In other words, after the treatment, although it was not statistically significant, a decreased tendency in anxiety was shown. In the HRV measurement, standard deviation normal to normal (SDNN), square root of the square root of the mean sum of squared differences between adjacent normal to normal intervals (RMSSD), and total power (TP) showed significant increase, Physical Stress Index (PSI) showed a significant reduction, and thus an improvement in the homeostatic control mechanism of the autonomic nervous system was ween. Conclusion : The MBSR program was applied to the patients showing anxiety and depression reaction after SAH treatment, and a reduction in depression symptoms and physiological reactions were observed. The application of the MBSR program may be considered as a new tool in improving the quality of life for patients after surgery.

PurposeAdoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas.Experimental designIn this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group). The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set.ResultsBetween December 2008 and October 2012, a total of 180 patients were randomly assigned to the CIK immunotherapy (n = 91) or control group (n = 89. In the intention-to-treat analysis set, median PFS was 8.1 months (95% confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one-sided log-rank, p = 0.0401). Overall survival did not differ significantly between two groups. Grade 3 or higher adverse events, health-related quality of life and performance status between two groups did not show a significant difference.ConclusionsThe addition of CIK cells immunotherapy to standard chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival.

No abstract

Inflammatory microenvironment signalling plays a crucial role in tumour progression (i.e. cancer cell proliferation, survival, angiogenesis and metastasis) in many types of human malignancies. However, the role of inflammation in brain tumour pathology remains poorly understood. Here, we report that interferon regulatory factor 7 is a crucial regulator of brain tumour progression and heterogeneity. Ectopic expression of interferon regulatory factor 7 in glioma cells promotes tumorigenicity, angiogenesis, microglia recruitment and cancer stemness in vivo and in vitro through induction of interleukin 6, C-X-C motif chemokine 1 and C-C motif chemokine 2. In particular, interferon regulatory factor 7-driven interleukin 6 plays a pivotal role in maintaining glioma stem cell properties via Janus kinase/signal transducer and activator of transcription-mediated activation of Jagged-Notch signalling in glioma cells and glioma stem cells derived from glioma patients.  Accordingly, the short hairpin RNA-mediated depletion of interferon regulatory factor 7 in glioma stem cells markedly suppressed interleukin 6-Janus kinase/signal transducer and activator of transcription-mediated Jagged-Notch-signalling pathway, leading to decreases in glioma stem cell marker expression, tumoursphere-forming ability, and tumorigenicity. Furthermore, in a mouse model of wound healing, depletion of interferon regulatory factor 7 suppressed tumour progression and decreased cellular heterogeneity. Finally, interferon regulatory factor 7 was overexpressed in patients with high-grade gliomas, suggesting its potential as an independent prognostic marker for glioma progression. Taken together, our findings indicate that interferon regulatory factor 7-mediated inflammatory signalling acts as a major driver of brain tumour progression and cellular heterogeneity via induction of glioma stem cell genesis and angiogenesis.

Laser-induced autofluorescence measurement of the brain was performed to assess its spectroscopic properties and to distinguish brain tumors from the normal tissues. The excitation-induced emission spectra were plotted on a 2-dimensional map, the excitation-emission matrix, to determine the excitation wavelengths most sensitive for the spectroscopic identification of brain tumors. The excitation-emission matrices of various types of human brain tumors and normal brain samples lead to the selection of three fluorescence peaks at 470, 520, and 630 nm, corresponding excitation light at 360, 440, and 490 nm, respectively for comparing the autofluorescence signatures of brain tissue. The fluorophores most likely related to each of these peaks are NAD(P)H, various flavins, and porphyrins, respectively. In vivo studies of rat gliomas showed that "NAD(P)H", "flavin", and "porphyrin" fluorescence were lower in gliomas than in normal brain. This finding suggests that there are certain relationship between brain tissue autofluorescence intensity and metabolic activity. In vitro human normal brain tissue fluorescence signals were lower in gray matter than in white matter and "NAD(P)H" fluorescence were lower in all measured human brain tumors than in normal brain. "Flavin" and "porphyrin" fluorescence in the neoplastic tissues was lower or higher than normal tissue depending on their nature. In conclusion, the fluorescence spectroscopic diagnostic system might be able to distinguish brain tumors from the normal brain tissue. The results of this study need to be verified and the investigation extended to human brain tumors in the operating room.