Surgical stabilization versus nonoperative treatment for flail and non-flail rib fracture patterns in patients with traumatic brain injury.

Purpose: Literature on outcomes after SSRF, stratified for rib fracture pattern is scarce in patients with moderate to severe traumatic brain injury (TBI; Glasgow Coma Scale ≤ 12). We hypothesized that SSRF is associated with improved outcomes as compared to nonoperative management without hampering neurological recovery in these patients.

Methods: A post hoc subgroup analysis of the multicenter, retrospective CWIS-TBI study was performed in patients with TBI and stratified by having sustained a non-flail fracture pattern or flail chest between January 1, 2012 and July 31, 2019.

A Phase II Trial of Imatinib Mesylate as Maintenance Therapy for Patients With Newly Diagnosed C-kit-positive Acute Myeloid Leukemia.

Introduction: Adults with acute myeloid leukemia (AML) have a high rate of remission; however, more than 50% relapse. C-kit is expressed in approximately 60% of patients with de novo AML and represents a potential therapeutic target.

Materials And Methods: Patients with newly diagnosed AML received 12 months of imatinib mesylate as maintenance therapy after the completion of post-remission therapy.

Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI).

Background: Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI.

Methods: A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019.

European genetic ancestry associated with risk of childhood ependymoma.

Background: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations.

Invasive fungal wound infection in an otherwise healthy trauma patient (Mucor Trauma).

Background: fungi are found ubiquitously in the environment and rarely cause infections in humans. Mucormycosis is typically seen in immunocompromised patients, but has been increasingly documented in previously healthy trauma patients. Mortality due to these infections can be high due to delayed diagnosis from a subtle clinical presentation and spread of infection by angioinvasion.

Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-analysis.

Background: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis.

Methods: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010 to 2013.

Application of mutagen sensitivity assay in a glioma case-control study.

Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls.

Geriatric (G60) trauma patients with severe rib fractures: Is muscle sparing minimally invasive thoracotomy rib fixation safe and does it improve post-operative pulmonary function?

Background: Patient outcomes after muscle sparing minimally invasive thoracotomy rib fixation (MSMIT-ORF) in geriatric G60 trauma patients remain poorly studied. This study determined the effect of MSMIT-ORF on pulmonary function (PFT). Non-operatively managed (NOM) patients were also described.

Brain- and brain tumor-penetrating disulfiram nanoparticles: Sequence of cytotoxic events and efficacy in human glioma cell lines and intracranial xenografts.

There is great interest in repurposing disulfiram (DSF), a rapidly metabolizing nontoxic drug, for brain cancers and other cancers. To overcome the instability and low therapeutic efficacy, we engineered passively-targeted DSF-nanoparticles (DSFNPs) using biodegradable monomethoxy (polyethylene glycol) d,l-lactic-co-glycolic acid (mPEG-PLGA) matrix. The physicochemical properties, cellular uptake and the blood brain-barrier permeability of DSFNPs were investigated.

A multicenter evaluation of the optimal timing of surgical stabilization of rib fractures.

Background: The optimal timing of surgical stabilization of rib fractures (SSRF) remains debated. We hypothesized that (1) demographic, radiologic, and clinical variables are associated with time to surgery and (2) shorter time to SSRF improves acute outcomes.

Methods: Prospectively collected SSRF databases from four trauma centers were merged and analyzed (2006-2016).

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.

Identifying augmented renal clearance in trauma patients: Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system.

Background: Augmented renal clearance (ARC) is common in trauma patients and associated with subtherapeutic antimicrobial concentrations. This study reported the incidence of ARC, identified ARC risk factors, and described a model to predict ARC (i.e.

New insights into estrogenic regulation of -methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or -benzylguanine indicates fresh avenues for therapy.

Endocrine therapy using estrogen receptor-α (ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with -methylguanine DNA methyltransferase (MGMT), a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines (MCF-7, T47D) and ER- negative cell lines (MDAMB-468, MDAMB-231), and established inhibitors of ER-α and MGMT, namely, ICI-182,780 (Faslodex) and O-benzylguanine, respectively, were used to study MGMT- ER interactions.

The importance of empiric antibiotic dosing in critically ill trauma patients: Are we under-dosing based on augmented renal clearance and inaccurate renal clearance estimates?

Background: An accurate assessment of creatinine clearance (CrCl) is essential when dosing medications in critically ill trauma patients. Trauma patients are known to experience augmented renal clearance (i.e.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk.

Geriatric trauma G-60 falls with hip fractures: A pilot study of acute pain management using femoral nerve fascia iliac blocks.

Background: Hip fractures due to falls cause significant morbidity and mortality among geriatric patients. A significant unmet need is an optimal pain management strategy. Consequently, patients are treated with standard analgesic care (SAC) regimens, which deliver high narcotic doses.

The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium.

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection.

Trauma-associated pneumonia: time to redefine ventilator-associated pneumonia in trauma patients.

Background: The high prevalence of ventilator-associated pneumonia (VAP) in trauma patients has been reported in the literature, but the reasons for this observation remain unclear. We hypothesize that trauma factors play critical roles in VAP etiology.

Methods: In this retrospective study, 1,044 ventilated trauma patients were identified from December 2010 to December 2013.

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells.

Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and inhibits JNK downstream signaling. In tumor cells, which frequently are characterized by constitutively high GSTP1 expression, GSTP1 undergoes phosphorylation by epidermal growth factor receptor (EGFR) at tyrosine residues 3, 7, and 198.

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q.

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors.