Biomimetic nanotherapeutics for targeted drug delivery to glioblastoma multiforme.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis and high mortality, with no curative treatment to date as limited trafficking across the blood-brain barrier (BBB) combined with tumor heterogeneity often leads to therapeutic failure. Although modern medicine poses a wide range of drugs that are otherwise efficacious in treating other tumors, they often do not achieve therapeutic concentrations in the brain, hence driving the need for more effective drug delivery strategies. Nanotechnology, an interdisciplinary field, has been gaining immense popularity in recent years for remarkable advancements such as nanoparticle (NP) drug carriers, which possess extraordinary versatility in modifying surface coatings to home in on target cells, including those beyond the BBB. In this review, we will be highlighting recent developments in biomimetic NPs in GBM therapy and how these allowed us to overcome the physiological and anatomical challenges that have long plagued GBM treatment.

Is there any survival benefit from post-operative radiation in brain metastases? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The benefits of adding upfront post-operative radiation, either whole-brain (WBRT) or cavity, after resection of brain metastases have been debated, particularly due to the long-term sequalae post radiation. We sought to compare the efficacy and safety between post-operative radiation versus resection alone. METHODS: We searched various biomedical databases from 1983 to 2018, for eligible randomized controlled trials (RCT). Outcomes studied were local recurrence (LR), overall survival (OS) and serious (Grade 3 + ) adverse events. We used the random effects model to pool outcomes. Methodological quality of each study was assessed using the Cochrane Risk of Bias tool. We employed the GRADE approach to assess the certainty of evidence. RESULTS: We included 5 RCTs comprising of 673 patients. The pooled odds ratio (OR) for LR is 0.26 (95% confidence interval (CI) 0.19-0.37, P < 0.001, GRADE certainty high), strongly supporting the use of post-operative radiation. Meta-regression analysis done comparing cavity and WBRT, did not show any difference in LR. The pooled hazard ratio (HR) for overall survival (OS) is 1.1 (95% CI 0.90-1.34, P = 0.37, GRADE certainty high). The treatment-related toxicities could not be pooled; the 2 studies which reported this did not find differences between the approaches. The risk of bias across the included studies was low. CONCLUSION: Our analysis confirms that upfront post-operative radiation significantly reduces the risk of LR. However, the lack of improvement in OS suggests that local control alone may not impact survival. Balancing local control, and neuro-cognitive effects of WBRT, cavity radiation seems to be a safe and effective option.

Impact of time to resumption of antithrombotic therapy on outcomes after surgical evacuation of chronic subdural hematoma: A multicenter cohort study.

BACKGROUND: The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. METHODS: Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. RESULTS: A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 - 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 - 47, range 4 - 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. CONCLUSIONS: Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.

Predictors of 30-day postoperative systemic complications in geriatric patients undergoing elective brain tumor surgery.

Little evidence exists to guide the preoperative selection of elderly brain tumor patients who are fit for surgery. We aimed to evaluate the safety of brain tumor resection in geriatric patients and identify predictors of postoperative 30-day systemic complications. We conducted a retrospective cohort study of 212 consecutive patients at or above the age of 60 years who underwent elective brain tumor resection between 2007 and 2017. The primary outcome measures analyzed were perioperative systemic complications within 30 days after the operation. A total of 212 geriatric brain tumor patients were included. Fifty-two (24.5%) had a 30-day systemic complication. Among them, 29 (13.7%) had systemic infections, 13 (6.1%) had perioperative seizures, 10 (4.7%) had syndrome of inappropriate antidiuretic hormone secretion (SIADH), five (2.4%) had deep venous thrombosis (DVT), four (1.9%) had perioperative stroke, three (1.4%) had acute myocardial infarction (AMI) and three (1.4%) had central nervous system (CNS) infections. One patient (0.5%) died. Perioperative stroke was predicted by previous stroke (p = 0.040), chronic liver disease (p < 0.001) and vestibular schwannoma (p = 0.002 with reference to meningiomas). Perioperative AMI was predicted by co-existing ischemic heart disease (p = 0.031). Systemic infection was predicted by female gender (p = 0.007) and preoperative Karnofsky Performance Scale (KPS) score < 70 (p = 0.019). DVT was predicted by GBM (p = 0.014). In conclusion, brain tumor surgery can be safe in carefully-selected geriatric patients. The risk factors identified in this study would be helpful to select suitable candidates for surgery.

A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy.

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.

Freehand Insertion of External Ventricular Drainage Catheter: Evaluation of Accuracy in a Single Center.

INTRODUCTION: External ventricular drain (EVD) placement is the gold standard for managing acute hydrocephalus. Freehand EVD, using surface anatomical landmarks, is performed for ventricular cannulation due to its simplicity and efficiency. This study evaluates accuracy and reason(s) for misplacements as few studies have analyzed the accuracy of freehand EVD insertion. PATIENTS AND METHODS: Preoperative and postoperative computed tomography scans of patients who underwent EVD insertion in 2014 were retrospectively reviewed. Diagnosis, Evans ratio, midline shift, position of burr hole, length of the catheter, and procedural complications were tabulated. The procedures were classified as satisfactory (catheter tip in the frontal horn ipsilateral lateral ventricle) and unsatisfactory. Unsatisfactory cases were further analyzed in relation to position of burr hole from midline and length of the catheter. RESULTS: Seventy-seven EVD placements in seventy patients were evaluated. The mean age of the patients was 57.5 years. About 83.1% were satisfactory placements and 11.7% were unsatisfactory in the contralateral ventricle, corpus callosum, and interhemispheric fissure. Nearly 5.2% were in extraventricular locations. Almost 2.6% EVD placements were complicated by hemorrhage and 1 catheter was reinserted. Suboptimal placements were significantly associated with longer intracranial catheter length. The mean length was 66.54 ± 10.1 mm in unsatisfactory placements compared to 58.32 ± 4.85 mm in satisfactory placements. Between the two groups, no significant difference was observed in Evans ratio, midline shift, surgeon's experience, distance of burr hole from midline, and coronal suture. CONCLUSION: Freehand EVD insertion is safe and accurate. In small number of cases, unsatisfactory placement is related to longer catheter length.

Coexisting Moyamoya Syndrome and Type 1 Diabetes Mellitus: A Case Report and Review of the Literature.

Moyamoya disease (MMD) is an incompletely understood malady that affects many age groups, primarily in a bimodal age distribution. We present a patient with the association of type 1 diabetes mellitus (type 1 DM) and MMD followed by a review of the existing literature. We found five papers that describe this association, in the form of one case report, one case series, and three retrospective reviews. Despite a poor understanding of the underlying pathophysiology, a clear association between autoimmune conditions and MMD appears to exist. Clinicians who manage such patients ought to be vigilant and have a high index of suspicion when young patients with type 1 DM present with new onset of neurological symptoms.