Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1) and a 5-month female (patient 2), affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC) greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents could lead to more effective and personalized anticancer treatments in the future.

A consecutive series of 330 severely head-injured patients was studied prospectively. All of the patients were treated with the same protocols by the same physicians and staff in the same intensive care unit. All of the patients had intracranial pressure (ICP) monitoring. Of the 330 patients, 100 were in the pediatric age group (0 to 19 years of age) and 230 were in the adult group (20 to 80 years of age). Statistical analyses were performed with regard to outcome, Glasgow Coma Scale (GCS) score, ICP course, and incidence of surgical lesions. The average emergency room GCS score as well as the 24-hour GCS score for each group was the same. The percentage of patients having ICP that was normal, increased but reducible, and increased but not reducible in each group was the same. The pediatric patients had a significantly higher percentage of good outcomes (43%) than the adult patients (28%) (p less than 0.01). They also had a significantly lower mortality rate (24%) than the adult patients (45%) (p less than 0.01). At 1 year following injury, 55% of pediatric patients had a good outcome compared to 21% of adults (p less than 0.001); this trend was evident at 3 months, with the same p value. Pediatric patients with normal ICP had a higher percentage of good outcomes (70%) than the adult patients with normal ICP (48%) (p less than 0.05). There was no significant difference in outcome in pediatric and adult patients with mass lesions or with increased ICP, regardless of whether or not the pressure was reducible. There was a much higher incidence of surgical mass lesions in adult patients (46%) than in pediatric patients (24%) (p less than 0.001).

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Introduction: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. Methods: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board–approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification components were examined. Results: Median follow-up was 8 months (range 3-49 months). For every 5% increase in in vitro CSC cell kill by TMZ, 12-month patient response (nonrecurrence of cancer) increased two-fold, OR = 2.2 (P = .016). Similar but somewhat less supported associations with the bulk tumor test were seen, OR = 2.75 (P = .07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR = 2.36 (P = .036), but a much attenuated remaining bulk tumor association, OR = 1.46 (P = .472). AUCs and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC = 0.989 [sensitivity = 100/specificity = 97], 0.972 [100/89], and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients w...

A case of T-1, T-2 disc herniation is reported. The patient presented with diminished hand strength, medial arm and shoulder pain, and medial arm, forearm, and hand paresthesias. After surgical decompression and removal of a disc fragment, the patient made a complete recovery. Routine cervical myelography was considered inadequate in view of this patient's symptoms. High thoracic myelography followed by computed tomographic scanning should be considered for patients with this presentation. Improved diagnosis with myelography and computed tomography is discussed.

Two cases of postoperative neurological deterioration following routine neurosurgical procedures are presented. In each instance, the patient was found to have hematological abnormalities present preoperatively consistent with vitamin B12 deficiency and to have undergone general anesthesia involving N2O. This caused inactivation of the remaining marginal stores of B12 with resultant neurological decompensation. The frequent use of N2O in general anesthesia and the significant incidence of B12 deficiency make it imperative that the surgeon be aware of this complication and its easy prevention. The preoperative recognition of B12 deficiency and N2O-induced neurological deterioration in patients with B12 deficiency is reviewed.

There are very few guidelines for the management of nonoperative head-injured patients. Rapid reversal guided by international normalized ratio values, Platelet Function Assays, computed tomography imaging of the head, and physical exam is suggested. The proposal presented in this paper enables patient management to begin quickly in a systematic approach, with the goal of achieving a significant decrease in the morbidity and mortality for the anticoagulated head-injured patient. Rapid reversal can potentially decrease mortality by as much as 38%.

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring in small cohorts of brain-injured patients suggests that this is not mirrored by alterations in cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well-tolerated in selected patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.