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. The primary outcome was mechanical ventilation-free days and secondary outcomes were in-hospital outcomes. In multivariable analysis, outcomes were assessed, stratified for rib fracture pattern. RESULTS: In total, 449 patients were analyzed. In patients with a non-flail fracture pattern, 25 of 228 (11.0%) underwent SSRF and in patients with a flail chest, 86 of 221 (38.9%). In multivariable analysis, ventilator-free days were similar in both treatment groups. For patients with a non-flail fracture pattern, the odds of pneumonia were significantly lower after SSRF (odds ratio 0.29; 95% CI 0.11-0.77; p = 0.013). In patients with a flail chest, the ICU LOS was significantly shorter in the SSRF group (beta, - 2.96 days; 95% CI - 5.70 to - 0.23; p = 0.034). CONCLUSION: In patients with TBI and a non-flail fracture pattern, SSRF was associated with a reduced pneumonia risk. In patients with TBI and a flail chest, a shorter ICU LOS was observed in the SSRF group. In both groups, SSRF was safe and did not hamper neurological recovery.

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. The primary objective was to determine whether this approach improved progression-free survival (defined as no relapse and no death) compared with historical controls. RESULTS: The median progression-free survival of patients < 60 years of age was 52.1 months (historical control, 13 months) and for patients ≥ 60 years of age was 10.7 months (historical control, 8 months). The median level of AF1q expression was high (9.59), and 84% of patients had moderate or high levels of drug-resistance factors. CONCLUSIONS: Imatinib maintenance therapy may improve the outcome of newly diagnosed patients with AML who are < 60 years of age.

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. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9-12) and severe (GCS score, ≤8) TBI. RESULTS: The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38-0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11-0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04-0.88; p = 0.034). CONCLUSION: In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE: Therapeutic, level IV.

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. METHODS: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). RESULTS: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients. CONCLUSIONS: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

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

BACKGROUND: Mucor 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. Early recognition and prompt treatment is critical for survival. We describe a case of invasive mucormycosis in a previously healthy trauma patient treated at a Level 1 trauma center. CASE REPORT: A 22-year-old male presented to the hospital after being involved in a motor vehicle accident. He sustained multiple traumatic injuries and developed multi-system organ failure within 48 hours of admission. He developed invasive, soft tissue mucormycosis (Rhizopus sp) at the laparotomy site, requiring multiple surgical debridements and prompt antifungal therapy. The fungus was also cultured from respiratory secretions and likely associated with his abdominal infection. We suspect the patient was predisposed to an invasive fungal infection in the setting of multi-system organ failure and multiple blood transfusions. The patient ultimately did well and continued to improve on follow up in the outpatient setting. CONCLUSIONS: Mucormycosis is a rare infection that has been increasingly documented in trauma patients. Early recognition together with prompt debridement and antifungal therapy is key to successful management. Understanding risk factors for post-traumatic mucormycosis should raise our index of suspicion and prompt early diagnosis and initiation of treatment. Aggressive debridement is a critical component of appropriate management due to the angioinvasive spread of the mucor fungi. This means frequent debridement beyond the demarcation of gangrenous tissue. The management of our patient demonstrates the importance of early recognition of the clinical presentation, prompt initiation of antifungal therapy, and aggressive debridement of the wound.

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. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for ≥6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. RESULTS: A history of daily aspirin use for ≥6 months was associated with a 38% lower glioma risk, compared with not having a history of daily use [adjusted meta-OR = 0.62; 95% confidence interval (CI), 0.54-0.70]. There was a significant duration-response trend (P = 1.67 × 10-17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR = 0.84; 95% CI, 0.70-1.02), but no association for NSAID use. CONCLUSIONS: Our study suggests that aspirin may be associated with a reduced risk of glioma. IMPACT: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

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. In this study, MSA was used to assess its applicability to a glioma case-control study and to test the hypothesis that subjects with glioma may have lower DNA repair capacity after exposure to selected potential human neurocarcinogens (i.e. acrylamide), compared to controls. Approximately 50 case and 50 control subjects were identified from a clinic-based study that investigated environmental risk factors for glioma, who completed an exposure survey, and had frozen immortalized lymphocytes available. A total of 50 metaphase spreads were read and reported for each participant. The association of case-control status with MSA for acrylamide, i.e. breaks per spread, was examined by multivariable logistic regression models. The mean number of breaks per slide was similar between hospital-based controls and cases. In addition, case-control status or exposure categories were not associated with the number of breaks per spread. Although the MSA has been shown as a useful molecular epidemiology tool for identifying individuals at higher risk for cancer, our data do not support the hypothesis that glioma patients have reduced DNA repair capacity in response to exposure to acrylamide. Further research is needed before the MSA is utilized in large-scale epidemiological investigations of alkylating agents.

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. METHODS: Medical records of G60 patients with severe rib fractures with PFTs measured before and after MSMIT-ORF were examined. Patient outcomes (MSMIT-ORF vs NOM) were adjusted in a multivariate logistic regression model. RESULTS: 64 patients underwent MSMIT-ORF, 135 were NOM patients. MSMIT-ORF treated patients showed improvements in PFTs on postoperative day 5, p = 0.001. After adjustment analysis, MSMIT-ORF was associated with increased hospital length of stay (OR 44.9; 95% CI, 9.8-205, p < 0.001), but a more favorable discharge disposition. There was no difference in the rates of pneumonia (p = 0.996) or death (p = 0.140). CONCLUSIONS: MSMIT-ORF is safe and improves pulmonary function in G60 trauma patients diagnosed with severe rib fractures. Future randomized control studies are needed for confirmation.

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. The DSFNPs were highly stable with a size of ∼70 nm with a >90% entrapment. Injection of the nanoparticles labeled with HITC, a near-infrared dye into normal mice and tumor-bearing nude mice followed by in vivo imaging showed a selective accumulation of the formulation within the brain and subcutaneous tumors for >24 h, indicating an increased plasma half-life and entry of DSF into desired sites. The DSFNPs induced a potent and preferential killing of many brain tumor cell lines in cytotoxicity assays. Confocal microscopy showed a quick internalization of the nanoparticles in tumor cells followed by initial accumulation in lysosomes and subsequently in mitochondria. DSFNPs induced high levels of ROS and led to a marked loss of mitochondrial membrane potential. Activation of the MAP-kinase pathway leading to a nuclear translocation of apoptosis-inducing factor and altered expression of apoptotic and anti-apoptotic proteins were also observed. DSFNPs induced a powerful and significant regression of intracranial medulloblastoma xenografts compared to the marginal efficacy of unencapsulated DSF. Together, we show that passively targeted DSFNPs can affect multiple targets, trigger potent anticancer effects, and can offer a sustained drug supply for brain cancer treatment through an enhanced permeability retention (EPR).

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). The independent variable was days from hospital admission to SSRF (early [<1 day], mid [1-2 days], and late [3-10 days]). Outcomes included length of operation, number of ribs repaired, prolonged (>24 hours) mechanical ventilation, pneumonia, tracheostomy, length of stay, and mortality. Multivariable logistic regression was used to control for significant differences in covariates between groups. RESULTS: Five hundred fifty-one patients were analyzed. The median time to SSRF was 1 day (range, 0-10); 207 (37.6%) patients were in the early group, 168 (30.5%) in the midgroup, and 186 (31.9%) in the late group. There was a significant shift toward earlier SSRF over the study period. Time to SSRF was significantly associated with study center (p < 0.01), year of surgery (p < 0.01), age (p = 0.02), mechanism of injury (p = 0.04), and body mass index (p = 0.02). Injury severity was not associated with time to surgery. Despite repairing the same median number of ribs (4; range, 1-13), median length of surgery was 68 minutes longer for the late as compared to the early group (p < 0.01). After controlling for the aforementioned significant covariates, each additional hospital day before SSRF was independently associated with a 31% increased likelihood of pneumonia (p < 0.01), a 27% increased likelihood of prolonged mechanical ventilation (p < 0.01), and a 26% increased likelihood of tracheostomy (p < 0.01). CONCLUSION: Surgical stabilization of rib fractures within 1 day of admission is associated with certain demographic and physiologic variables. After controlling for confounding factors, early SSRF was accomplished using less operative time, and was associated with favorable outcomes. When indicated and feasible, SSRF should occur as early as possible. LEVEL OF EVIDENCE: Therapy, level III.

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., ARCTIC) that is specific to trauma patients. METHODS: Consecutive trauma patients who were admitted to the intensive care unit between March 2015 and January 2016 and had a measured creatinine clearance (CrCl) were considered for inclusion. Patients were excluded if their serum creatinine (SCr) was greater than 1.3 mg/dL. ARC was defined as a measured CrCl of 130 mL/min or greater. Demographic and trauma-specific variables were then compared, and multivariate analysis was performed. Using these results, a weighted scoring system was constructed and evaluated using receiver operating characteristic curve analysis. ARCTIC score cutoffs were chosen based on sensitivity, specificity, positive predictive value, and negative predictive value. The derived scoring system was then compared to a previously published scoring system for accuracy. RESULTS: There were 133 patients with a mean age of 48 ± 19 years and SCr of 0.8 ± 0.2 mg/dL. The mean measured CrCl was 168 ± 65 mL/min, and the incidence of ARC was 67%. Multivariate analysis revealed the following risk factors for ARC (age, <56: odds ratios [OR], 58.3; 95% confidence interval [CI], 5.2-658.9; age, 56 to 75: OR, 13.5; 95% CI, 1.2-151.7), SCr less than 0.7 mg/dL (OR, 12.5; 95% CI, 3-52.6), and male sex (OR, 6.9; 95% CI, 1.9-24.9). Using these results, the ARCTIC scoring system was: 4 points if younger than 56 years, 3 points if aged 56 years to 75 years, 3 points if SCr less than 0.7 mg/dL, and 2 points if male sex. Receiver operating characteristic curve analysis revealed an area (95% CI) of 0.813 (0.735-0.892) (p < 0.001). An ARCTIC score of 6 or higher had a sensitivity, specificity, positive predictive value, and negative predictive value of 0.843, 0.682, 0.843, and 0.682, respectively. CONCLUSION: The incidence of ARC in trauma patients is high. The ARCTIC score represents a practical, pragmatic system that can be easily applied at the bedside. An ARCTIC score of 6 or higher represents an appropriate cutoff to screen for ARC where antimicrobial adjustments should be considered. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

New insights into estrogenic regulation of O6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or O6-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 O6-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 O6-benzylguanine, respectively, were used to study MGMT- ER interactions. The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements (EREs) and two antioxidant-responsive elements (AREs). MGMT expression was upregulated by estrogen, downregulated by tamoxifen in Western blot and promoter-linked reporter assays. Similarly, both transient and stable transfections of Nrf-2 (nuclear factor-erythroid 2-related factor-2) increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this drug-resistance determinant. Of the different ER-α antagonists tested, the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose, time and ER-α dependent manner, similar to O6-benzylguanine. Interestingly, fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O6-benzylguanine also induced a specific loss of ER-α and MGMT proteins in MCF-7 and T47D breast cancer cells with similar kinetics. Immunoprecipitation revealed a specific association of ER-α and MGMT proteins in breast cancer cells. Furthermore, silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-α proteins. The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated. Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents, namely, temozolomide and BCNU by 3 to 4-fold in ER-α positive cells, but not in ER-negative cells. We conclude that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation. The findings offer a clear rationale for combining alkylating agents with endocrine therapy.

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., CrCl ≥130 mL/min), and the use of CrCl estimations may be inaccurate leading to under-/over-dosing of medications. As such, our Level I trauma center began using measured CrCl from timed urine collections to better assess CrCl. This study sought to determine the prevalence of augmented renal clearance and the accuracy of calculated CrCl in critically ill trauma patients. METHODS: This observational study evaluated consecutive ICU trauma patients with a timed 12-hour urine collection for CrCl. Data abstracted were patient demographics, trauma-related factors, and CrCl. Augmented renal clearance was defined as measured CrCl ≥130 mL/min. Bias and accuracy were determined by comparing measured and estimated CrCl using the Cockcroft-Gault and other formulas. Bias was defined as measured minus calculated CrCl, and accuracy was calculated CrCl that was within 30% of measured. RESULTS: There were 65 patients with a mean age of 48 years, serum creatinine (SCr) of 0.8 ± 0.3 mg/dL, and injury severity score of 22 ± 14. The incidence of augmented renal clearance was 69% and was more common when age was <67 years and SCr <0.8 mg/dL. Calculated CrCl was significantly lower than measured (131 ± 45 mL/min vs. 169 ± 70 mL/min, p < 0.001) and only moderately correlated (r = 0.610, p < 0.001). Bias was 38 ± 56 mL/min, which was independent of age quartile (p = 0.731). Calculated CrCl was inaccurate in 33% of patients and trauma-related factors were not predictive. CONCLUSION: The prevalence of augmented renal clearance in critically ill trauma patients is high. Formulas used to estimate CrCl in this population are inaccurate and could lead to under-dosing of medications. Measured CrCl should be used in this setting to identify augmented renal clearance and allow for more accurate estimates of renal function. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.

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. METHODS: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. RESULTS: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. CONCLUSION: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. IMPACT: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention.

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. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

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. However, narcotics are associated with delirium as well as gastrointestinal and respiratory failure risks. The purpose of this pilot study was to determine the safety and effectiveness of ultrasound-guided continuous compartmental fascia iliaca block (CFIB) in patients 60 years or older with hip fractures in comparison with SAC alone. METHODS: We performed a retrospective study of 108 patients 60 years or older, with acute pain secondary to hip fracture (2012-2013). Patient variables were age, sex, comorbidities, and Injury Severity Score (ISS). Primary outcome was pain scores; secondary outcomes included hospital length of stay, discharge disposition, morbidity, and mortality. Statistical analysis was performed using (IBM SPSS version 22). For group comparison (SAC vs. SAC + CFIB) median test, repeated-measures analysis and Student's t test of transformed pain scores were used. RESULTS: Sixty-four patients received SAC only, and 44 patients received SAC + CFIB. Each CFIB placement was successful on first attempt without complications. Median time from emergency department arrival to block placement was 12.5 hours (interquartile range, 4-22 hours). Patients who received SAC + CFIB had significantly lower pain score ratings than patients treated with SAC alone. There were no differences in inpatient morbidity and mortality rates. Patients treated with SAC + CFIB were discharged home more often (p < 0.05). CONCLUSION: Ultrasound-guided CFIB is safe, practical, and readily integrated into the G-60 service for improved pain management of hip fractures. We are now conducting a prospective randomized control trial to confirm our observations. LEVEL OF EVIDENCE: Therapeutic study, level IV.

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. Patient-level trauma factors were used to predict pneumonia as study endpoint. RESULTS: Ninety-five of the 1,044 ventilated trauma patients developed pneumonia. Rib fractures, pulmonary contusion, and failed prehospital intubation were significant predictors of pneumonia in a multivariate model. CONCLUSIONS: It is time to redefine VAP in trauma patients based on the effect of rib fractures, pulmonary contusions, and failed prehospital intubations. The Centers for Disease Control and Prevention definition of VAP needs to be modified to reflect the effect of trauma factors in the etiology of trauma-associated pneumonia.