Risk of death in patients with post-traumatic cerebrospinal fluid leakage—Analysis of 1773 cases

AbstractBackgroundPost-traumatic cerebrospinal fluid (CSF) leakage is one of the most troublesome conditions associated with head trauma. CSF fistulae, meningitis/central nervous infection, or even death may accompany it. Few studies have discussed post-traumatic CSF leakage as a risk factor in mortality following head trauma. We conducted this cohort study to examine the issue.MethodsWe reviewed the records in the Taiwan Traumatic Brain Injury (TBI) Registry System between 1993 and 2008. The study group included patients with acute TBI and post-traumatic CSF leakage, and the control group included cases with TBI but without CSF leakage, selected randomly at a 5:1 ratio with respect to the study group. The demographic data, Glasgow Coma Scale, brain computerized tomography, association of skull fractures and intracranial lesions, and 1-year mortality rates between these two cohorts were reviewed meticulously and analyzed statistically.ResultsOf 174,236 cases, 1773 with post-traumatic CSF leakage were included in the study group, and 8865 cases in the control group. Of the total 10,638 sampled cases, 406 (3.8%) died during the 1-year follow-up period, 159 (9.0%) cases in the CSF leakages group, and 247 (2.8%) in the control group. The patients with CSF leakage had a significantly higher mortality rate within 1 year (adjusted hazard ratio = 1.44, p < 0.001) than those without. We divided the CSF leakage group into three subgroups: otorrhea (n = 568), rhinorrhea (n = 302), and tension pneumocephalus (n = 903). The mortality rates were 8.5% (48/568) in the otorrhea subgroup, 10.9% (33/302) in the rhinorrhea subgroup, and 8.6% (78/903) in the tension pneumocephalus subgroup. The cases with CSF rhinorrhea had a significantly higher mortality rate than the other two subgroups (p < 0.05). All three subgroups had significantly higher mortality rates than the control group during the 1-year follow-up period (adjusted hazard ratios = 2.29, 1.35, and 1.32 in the rhinorrhea, tension pneumocephalus, and otorrhea subgroups, respectively).ConclusionPost-traumatic CSF leakages had higher mortality rates than those without CSF leakages in TBI cases, and the cases with CSF rhinorrhea had worse outcomes compared with CSF leakages with pneumocephalus or otorrhea

Ancient schwannoma of thoracic spine in a schizophrenic patient with somatic delusion

Ancient schwannoma is a rare variant of schwannoma characterized by histopathologic degenerative changes, which are thought to be the result of long-term tumor growth and aging. However, ancient schwannoma in the spinal canal is particularly rare. We report a case of thoracic spine intradural extramedullary ancient schwannoma in a schizophrenic patient, who kept saying that “something in his back was giving him electric shock” for a long time. Unfortunately, this complaint was misinterpreted as somatic delusion symptoms. A spinal cord tumor was taken into consideration only after paraparesis developed. We have highlighted this case to remind every clinician to remain alert about the possibility of organic disease while treating patients with psychotic disorder history. Thorough neurological examination is required to avoid misdiagnosis. Spinal canal schwannoma can be totally removed successfully with good functional outcome and prognosis

Comparison of Percutaneous Endoscopic Lumbar Discectomy and Open Lumbar Surgery for Adjacent Segment Degeneration and Recurrent Disc Herniation

Objective. The goal of the present study was to examine the clinical results of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar surgery for patients with adjacent segment degeneration (ASD) and recurrence of disc herniation. Methods. From December 2011 to November 2013, we collected forty-three patients who underwent repeated lumbar surgery. These patients, either received PELD (18 patients) or repeated open lumbar surgery (25 patients), due to ASD or recurrence of disc herniation at L3-4, L4-5, or L5-S1 level, were assigned to different groups according to the surgical approaches. Clinical data were assessed and compared. Results. Mean blood loss was significantly less in the PELD group as compared to the open lumbar surgery group P<0.0001. Hospital stay and mean operating time were shorter significantly in the PELD group as compared to the open lumbar surgery group P<0.0001. Immediate postoperative pain improvement in VAS was 3.5 in the PELD group and −0.56 in the open lumbar surgery group P<0.0001. Conclusion. For ASD and recurrent lumbar disc herniation, PELD had more advantages over open lumbar surgery in terms of reduced blood loss, shorter hospital stay, operating time, fewer complications, and less postoperative discomfort

Elimination of Cancer Stem-Like Cells and Potentiation of Temozolomide Sensitivity by Honokiol in Glioblastoma Multiforme Cells

<div><p>Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as <i>SMO</i>, <i>Notch3</i> and <i>IHH (Indian Hedgehog)</i>. Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC₅₀ were 5.3±0.72 and 11±1.1 μM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5±0.22% down to 0.3±0.02% and 0.2±0.01% at doses of 2.5 μM and 5 μM, respectively. The SP cells appeared to have higher expression of <i>O</i>⁶-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor <i>O</i>⁶-benzylguanine (<i>O</i>⁶-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was accompanied with the higher induction of apoptosis, greater down-regulation of <i>Notch3</i> as well as its downstream <i>Hes1</i> expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment.</p></div

Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells

<div><p>Background</p><p>Medulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity.</p><p>Methods</p><p>We detected the expression of inhibitors of apoptosis proteins (IAPs) in MB and CD133+ MB cell lines and MB tissues using immunoblotting and immunohistochemical staining. The antitumor effects of inhibitors against IAPs on MB or CD133+ MB cells were evaluated by MTT assay, Annexin V/PI analysis, and caspase-3/7 activity. Autophagy was assessed by the conversion of light chain (LC) 3-I to LC3-II and Cyto-ID autophagy detection kit.</p><p>Results</p><p>MB cells showed higher expression of IAPs compared to normal astrocytes and normal brain tissues. Conventional chemotherapeutic agents combined with small-molecule IAP inhibitors (LCL161 or LBW242) showed a synergistic effect in MB cells. Combined treatments triggered apoptosis in MB cells through activation of caspase-3/7 and autophagic flux simultaneously. In addition, we found that CD133+ MB cells with features of cancer stem cells displayed higher levels of X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 1/2 (cIAP1/2), and were hypersensitive to treatment with IAP inhibitors.</p><p>Conclusions</p><p>These results shed light on the biological effects of combination therapy on MB cells and illustrate that IAP inhibitors are more effective for CD133+ stem-like MB cells.</p></div

IAP inhibitors sensitize CD133+ stem-like MB cells to chemotherapeutic agents.

<p>(A) CD133+ cells isolated from DAOY and D283MED cell lines were cultured in 96-well plates and treated with different concentrations of vincristine or cisplatin combined with or without IAP inhibitors (LCL161 10 μM) for 72 hr. The cell viability was measured by MTT assay. (B)(C) Cells were treated with chemotherapeutic drug (vincristine or cisplatin) or in combination with IAP inhibitors for 72 hours. Apoptosis was detected by Annexin V/PI and FACS. The bar graphs indicate the proportion of induced apoptosis. Similar results were obtained by three independent experiments. (*p < 0.05, **p < 0.001, and ***p < 0.005).</p

Combination of IAP inhibitors and chemotherapeutic agents promotes autophagy-dependent apoptosis.

<p>(A) DAOY and D283MED cells were treated with chemotherapeutic agent (vincristine or cisplatin) only or in combination with DMSO, LCL161 (10μM) or LBW242 (10μM) for 72 hr. Autophagic flux was determined by cyto-ID and analyzed by FACS. (B) Autophagic flux was based on percentage of right shift and has been shown in bar graphs (*p < 0.05, **p < 0.001, and ***p < 0.005). (C) LC3-I/II conversion was determined by immunoblotting after these treatments for 72 hr. (D) (E) The autophagy inhibitor (chloroquine, 10 μM) reduced combination therapy-induced apoptosis, as determined by Annexin V/PI and FACS. The bar graphs show the proportions of Annexin V positive cells (*p < 0.05, **p < 0.001, and ***p < 0.005).</p

Addition of IAP inhibitors enhances chemotherapy-induced apoptosis in MB cells.

<p>DAOY and D283MED cells were treated with vincristine (1.25 nM for DAOY, 2.5 nM for D283MED) or cisplatin (0.3125 μM for DAOY, 0.625 μM for D283MED), or combination of the chemotherapeutic drug with an IAP inhibitor (LCL161 or LBW242, 10 μM) for 72 hr. (A)(B) Apoptosis was assessed by Annexin V/PI and FACS. The apoptotic proportions (Annexin V positive cells) are shown in bar graphs. (C) MB cells were treated with these chemotherapeutic agents combined with or without IAP inhibitors for 72 hr, and cell lysates were then subjected to immunoblotting analysis. (D) DAOY cells were treated with vincristine or cisplatin only, or in combination with LCL161 for 72 hr. The bar graph represents Caspase-3/7 activity, which was analyzed by FACS. The error bars represent mean ± SEM (*p < 0.05, **p < 0.001, and ***p < 0.005).</p