Novel omeprazole delayed release orally disintegrating tablets for enhanced patient compliance: a case of model informed formulation development.

The advanced simulation tools, such as physiologically based biopharmaceutics models (PBBM) or physiologically based pharmacokinetic models (PBPK), play critical role in model informed formulation development. This approach has been successfully implemented in the present case for development of novel omeprazole delayed-release orally disintegrating tablets (ODT) formulation, aimed to enhance patient compliance.PBBM was developed using physicochemical, biopharmaceutical, and dissolution data.

Reoperation in adult patients with recurrent glioblastoma: A matched cohort analysis.

Background: Despite maximal safe cytoreductive surgery and postoperative adjuvant therapies, glioblastoma (GBM) inevitably recurs and leads to deterioration of neurological status and eventual death. There is no consensus regarding the benefit of repeat resection for enhancing survival or quality of life in patients with recurrent GBM. We aimed to examine if reoperation for GBM recurrence incurs a survival benefit as well as examine its complication profile.

Using child-friendly movie stimuli to study the development of face, place, and object regions from age 3 to 12 years.

Scanning young children while they watch short, engaging, commercially-produced movies has emerged as a promising approach for increasing data retention and quality. Movie stimuli also evoke a richer variety of cognitive processes than traditional experiments, allowing the study of multiple aspects of brain development simultaneously. However, because these stimuli are uncontrolled, it is unclear how effectively distinct profiles of brain activity can be distinguished from the resulting data.

A Novel University of North Carolina Laparoscopic Ventral Hernia Repair Simulator.

Simulation plays an important role in surgical training. We developed a simulator for laparoscopic ventral hernia repair (LVHR) surgery based on porcine tissue, characterized by low cost and high reality. Our LVHR model is based on porcine tissue mounted in a human mannequin.

A CD133-AKT-Wnt signaling axis drives glioblastoma brain tumor-initiating cells.

Mechanistic insight into signaling pathways downstream of surface receptors has been revolutionized with integrated cancer genomics. This has fostered current treatment modalities, namely immunotherapy, to capitalize on targeting key oncogenic signaling nodes downstream of a limited number of surface markers. Unfortunately, rudimentary mechanistic understanding of most other cell surface proteins has reduced the clinical utility of these markers.

Bmi1 regulates human glioblastoma stem cells through activation of differential gene networks in CD133+ brain tumor initiating cells.

Purpose: Glioblastoma (GBM) is the most aggressive adult brain cancer, with a 15 month median survivorship attributed to the existence of treatment-refractory brain tumor initiating cells (BTICs). In order to better understand the mechanisms regulating the tumorigenic properties of this population, we studied the role of the polycomb group member BMI1 in our patient-derived GBM BTICs and its relationship with CD133, a well-established marker of BTICs.

Methods: Using gain and loss-of-function studies for Bmi1 in neural stem cells (NSCs) and patient-derived GBM BTICs respectively, we assessed in vitro self-renewal and in vivo tumor formation in these two cell populations.

Discrepancies Between Patient and Surgeon Expectations of Surgery for Sciatica: A Challenge for Informed Decision Making?

Study Design: Qualitative study.

Objective: The objective of this study was to compare the perceptions of patients and surgeons regarding the risks and benefits of lumbar decompressive surgery for sciatica following a consultation meeting.

Summary Of Background Data: Evidence regarding pain improvement in patients following lumbar decompressive surgery for sciatica is inconsistent.

Therapeutic Targeting of the Premetastatic Stage in Human Lung-to-Brain Metastasis.

Brain metastases (BM) result from the spread of primary tumors to the brain and are a leading cause of cancer mortality in adults. Secondary tissue colonization remains the main bottleneck in metastatic development, yet this "premetastatic" stage of the metastatic cascade, when primary tumor cells cross the blood-brain barrier and seed the brain before initiating a secondary tumor, remains poorly characterized. Current studies rely on specimens from fully developed macrometastases to identify therapeutic options in cancer treatment, overlooking the potentially more treatable "premetastatic" phase when colonizing cancer cells could be targeted before they initiate the secondary brain tumor.

Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma.

Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM).

Massive lumbar spine hematoma post-spinal tap.

Background: Lumbar puncture is a well-known procedure. The indications for lumbar puncture vary among different medical and surgical disciplines, though obtaining a sample for cerebrospinal fluid analysis is the most common one. A normal coagulation profile is crucial prior to pursing the procedure.

RNAi screen identifies essential regulators of human brain metastasis-initiating cells.

Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs).

Standardized, Interdepartmental, Simulation-Based Central Line Insertion Course Closes an Educational Gap and Improves Intern Comfort with the Procedure.

Central line placement is a common procedure, routinely performed by junior residents in medical and surgical departments. Before this project, no standardized instructional course on the insertion of central lines existed at our institution, and few interns had received formal ultrasound training. Interns from five departments participated in a simulation-based central line insertion course.

Simulation Model for Laparoscopic Foregut Surgery: The University of North Carolina Foregut Model.

Background: A significant gap presently exists between box-lap and virtual-reality simulators and live surgery. Live animal and cadaver use has significant downsides. We have developed a high fidelity, real tissue simulator that allows training in laparoscopic foregut operations.

Patients' Attitudes Toward Nonphysician Screening of Low Back and Low Back Related Leg Pain Complaints Referred for Surgical Assessment.

Study Design: A questionnaire survey.

Objective: The aim of this study was to explore patient attitudes toward screening to assess suitability for low back surgery by nonphysician health care providers.

Summary Of Background Data: Canadian spine surgeons have shown support for nonphysician screening to assess and triage patients with low back pain and low back related leg pain.

Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties.

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution.

The identification of human pituitary adenoma-initiating cells.

Classified as benign central nervous system (CNS) tumors, pituitary adenomas account for 10% of diagnosed intracranial neoplasms. Although surgery is often curative, patients with invasive macroadenomas continue to experience significant morbidity and are prone to tumor recurrence. Given the identification of human brain tumor-initiating cells (TICs) that initiate and maintain tumor growth while promoting disease progression and relapse in multiple CNS tumors, we investigated whether TICs also drive the growth of human pituitary adenomas.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis.

Importance: Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition.

Objective: To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke.

A novel stem cell culture model of recurrent glioblastoma.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with average disease relapse at 9 months and median survival rarely extending beyond 15 months. Brain tumor stem cells (BTSCs) have been implicated in not only initiating GBM but also conferring resistance to therapy. However, it is not clear whether the BTSC population that initiates tumor growth is also responsible for GBM recurrence.

STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation.

Brain metastases (BM) represent the most common tumor to affect the adult central nervous system. Despite the increasing incidence of BM, likely due to consistently improving treatment of primary cancers, BM remain severely understudied. In this study, we utilized patient-derived stem cell lines from lung-to-brain metastases to examine the regulatory role of STAT3 in brain metastasis initiating cells (BMICs).

Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor-Initiating Cells.

Purpose: Clonal evolution of cancer may be regulated by determinants of stemness, specifically self-renewal, and current therapies have not considered how genetic perturbations or properties of stemness affect such functional processes. Glioblastoma-initiating cells (GICs), identified by expression of the cell surface marker CD133, are shown to be chemoradioresistant. In the current study, we sought to elucidate the functional role of CD133 in self-renewal and identify compounds that can specifically target this CD133(+) treatment-refractory population.

Cervical spine clearance in obtunded patients after blunt traumatic injury: a systematic review.

Background: Cervical spine clearance protocols are controversial for unconscious patients after blunt traumatic injury and negative findings on computed tomography (CT).

Purpose: To review evidence about the utility of different cervical spine clearance protocols in excluding significant cervical spine injury after negative CT results in obtunded adults with blunt traumatic injury.

Data Sources: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were searched from January 2000 through November 2014.

Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis.

Background: Optimal extent of surgical resection (EOR) of high-grade gliomas (HGGs) remains uncertain in the elderly given the unclear benefits and potentially higher rates of mortality and morbidity associated with more extensive degrees of resection.

Methods: We undertook a meta-analysis according to a predefined protocol and systematically searched literature databases for reports about HGG EOR. Elderly patients (≥60 y) undergoing biopsy, subtotal resection (STR), and gross total resection (GTR) were compared for the outcome measures of overall survival (OS), postoperative karnofsky performance status (KPS), progression-free survival (PFS), mortality, and morbidity.

Developing sustainable global health technologies: insight from an initiative to address neonatal hypothermia.

Relative to drugs, diagnostics, and vaccines, efforts to develop other global health technologies, such as medical devices, are limited and often focus on the short-term goal of prototype development instead of the long-term goal of a sustainable business model. To develop a medical device to address neonatal hypothermia for use in resource-limited settings, we turned to principles of design theory: (1) define the problem with consideration of appropriate integration into relevant health policies, (2) identify the users of the technology and the scenarios in which the technology would be used, and (3) use a highly iterative product design and development process that incorporates the perspective of the user of the technology at the outset and addresses scalability. In contrast to our initial idea, to create a single device, the process guided us to create two separate devices, both strikingly different from current solutions.

Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data: Clinic article.

Object: Information pertaining to the natural history of intramedullary spinal cord cavernous malformations (ISCCMs) and patient outcomes after surgery is scarce. To evaluate factors associated with favorable outcomes for patients with surgically and conservatively managed ISCCMs, the authors performed a systematic review and metaanalysis of the literature. In addition, they included their single-center series of ISCCMs.

Transformation of Merkel cell carcinoma to ganglioneuroblastoma in intracranial metastasis.

Merkel cell carcinoma is an aggressive neuroendocrine tumor occasionally demonstrating aberrant differentiation to other epithelial and nonepithelial cell lines. We describe a case of Merkel cell carcinoma displaying unique patterns of differentiation in the primary focus and brain metastasis. The skin primary was almost uniformly small cell carcinoma positive for epithelial and neuroendocrine markers, with a few glial fibrillary acidic protein- and cytokeratin 20-positive cells.