Comparison of Antimicrobial Activity Between Bacitracin-Soaked Sutures and Triclosan Coated Suture.

BACKGROUND: With the easily available option for surgeons to soak their suture in antibiotic irrigation solution intraoperatively in mind, this study was designed to evaluate the ability of suture soaked in bacitracin irrigation solution to inhibit the growth of Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. MATERIALS AND METHODS: Using standard experimental procedure, sterile suture was soaked in Bacitracin, and dried for 10 min or 6 h, incubated for 24 h on inoculated plates, and examined for zone of inhibition around the suture. This was compared to control unsoaked suture and antimicrobial suture (AMS) currently on the market to determine if the minor intraoperative procedural change of placing suture in antibiotic irrigation solution instead of on the sterile table could confer comparable antimicrobial activity. RESULTS: The study found the Bacitracin-soaked suture (BSS) consistently inhibited the growth of the test organisms. For both organisms, the BSS exhibited a significantly larger zone of inhibition compared to the unsoaked control suture (P < 0.0001). However, both the AMS currently on the market, and a bacitracin aliquot, exhibited significantly larger zones of inhibition compared to both drying times of the BSS (P < 0.0001). CONCLUSIONS: Placing sutures in a bacitracin irrigation solution intraoperatively instead of directly on the sterile table can achieve some of the in vitro antimicrobial effect seen from AMS currently on the market. This may result in reduced rates of surgical site infections and associated costs without major procedural change and at reduced overhead.

Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial.

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world.

Colloid cyst: a case report.

Colloid cysts are a rare clinical finding with a unique clinical presentation: non-specific paroxysmal headaches. The current recommended treatment is microsurgery, which poses the greatest risk to the patient but allows complete removal of the cyst to prevent recurrence. A 41-year old man presented with a colloid cyst located in the foramen of Monro causing obstructive hydrocephalus. He had paroxysmal headaches and memory and personality changes. Transcortical transventricle microsurgery was performed to remove the entire cyst. A temporary shunt was placed to prevent post-operative hydrocephalus. Normal neurological function returned upon cyst removal.

Neurologic Assessment of the Neurocritical Care Patient.

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.

Proposal for the Rapid Reversal of Coagulopathy in Patients with Nonoperative Head Injuries on Anticoagulants and/or Antiplatelet Agents: A Case Study and Literature Review.

BACKGROUND: Emergency room physicians, trauma teams, and neurosurgeons are seeing increasing numbers of head-injured patients on anticoagulants, many of whom are nonoperative. Head injury and anticoagulation can lead to devastating consequences. These patients need immediate evaluation and often reversal of anticoagulation in order to decrease their high rates of morbidity and mortality. OBJECTIVE: To review data on the prevalence, risks, treatment, and complications of head-injured anticoagulated patients and provide a proposal for their anticoagulant management, and imaging requirements. METHODS: A PubMed database search was performed for articles on the prevalence, risks, treatment, and complications of patients who have sustained a head injury while on anticoagulant or antiplatelet agents. RESULTS: A total of 1877 articles were found, of which 64 were selected for use based on direct relevance, information quality, and contribution of the article to the current understanding of anticoagulated head injury patients. CONCLUSION: 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%.

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients.

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 was improved by 11% when using the CSC test in conjunction with the bulk test (risk reclassification nonevent net reclassification improvement [NRI] and overall NRI=0.111, P=.030). Median recurrence time was 20 months for patients with a positive (>40% cell kill) CSC test versus only 3 months for those with a negative CSC test, whereas median recurrence time was 13 months versus 4 months for patients with a positive (>55% cell kill) bulk test versus negative. Similar favorable results for the CSC test were observed for PFS and OS outcomes. Panel results across 14 potential other treatments indicated that 34/41 (83%) potentially more optimal alternative therapies may have been chosen using CSC results, whereas 27/41 (66%) alternative therapies may have been chosen using bulk tumor results. CONCLUSIONS: The ChemoID CSC drug response assay has the potential to increase the accuracy of bulk tumor assays to help guide individualized chemotherapy choices. GBM cancer recurrence may occur quickly if the CSC test has a low in vitro cell kill rate even if the bulk tumor test cell kill rate is high.

Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

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.