RNA targets of multitargeted RNA-binding proteins (RBPs) can be studied by various methods including mobility shift assays, iterative in vitro selection techniques and computational approaches. These techniques, however, cannot be used to identify the cellular context within which mRNAs associate, nor can they be used to elucidate the dynamic composition of RNAs in ribonucleoprotein (RNP) complexes in response to physiological stimuli. But by combining biochemical and genomics procedures to isolate and identify RNAs associated with RNA-binding proteins, information regarding RNA-protein and RNA-RNA interactions can be examined more directly within a cellular context. Several protocols--including the yeast three-hybrid system and immunoprecipitations that use physical or chemical cross-linking--have been developed to address this issue. Cross-linking procedures in general, however, are limited by inefficiency and sequence biases. The approach outlined here, termed RNP immunoprecipitation-microarray (RIP-Chip), allows the identification of discrete subsets of RNAs associated with multi-targeted RNA-binding proteins and provides information regarding changes in the intracellular composition of mRNPs in response to physical, chemical or developmental inducements of living systems. Thus, RIP-Chip can be used to identify subsets of RNAs that have related functions and are potentially co-regulated, as well as proteins that are associated with them in RNP complexes. Using RIP-Chip, the identification and/or quantification of RNAs in RNP complexes can be accomplished within a few hours or days depending on the RNA detection method used.

abbreviatioNs EOR = extent of resection; GBM = glioblastoma; GTR = gross-total resection; HR = hazard ratio; KPS = Karnofsky Performance Scale; RT = radiotherapy; SRS = stereotactic radiosurgery; STR = subtotal resection; TMZ = temozolomide. obJective The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. methods A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. results A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio coNclusioN This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevaciz...

IMPORTANCE There are limited data on which factors affect the critical and complex decision to withdraw life-supporting treatment (LST) in patients with severe traumatic brain injury (sTBI).OBJECTIVE To determine demographic and clinical factors associated with the decision to withdraw LST in patients with sTBI. DESIGN, SETTING, AND PARTICIPANTSThis retrospective analysis of inpatient data from more than 825 trauma centers across the US in the American College of Surgeons Trauma Quality Improvement Program database from January 2013 to December 2015 included adult patients with sTBI and documentation of a decision regarding withdrawal of LST (WLST). Data analysis was conducted in September 2019. MAIN OUTCOMES AND MEASURES Factors associated with WLST in sTBI.RESULTS A total of 37931 patients (9817 women [25.9%]) were included in the multivariable analysis; 7864 (20.7%) had WLST. Black patients (4806 [13.2%]; odds ratio [OR], 0.66; 95% CI, 0.59-0.72; P < .001) and patients of other race (4798 [13.2%]; OR, 0.83; 95% CI, 0.76-0.91; P < .001) were less likely than white patients (26 864 [73.7%]) to have WLST. Patients from hospitals in the Midwest (OR, 1.12; 95% CI, 1.04-1.20; P = .002) or Northeast (OR, 1.23; 95% CI, 1.13-1.34; P < .001) were more likely to have WLST than patients from hospitals in the South. Patients with Medicare (OR, 1.55; 95% CI, 1.43-1.69; P < .001) and self-pay patients (OR, 1.36; 95% CI, 1.25-1.47; P < .001) were more likely to have WLST than patients with private insurance. Older patients and those with lower Glasgow Coma Scale scores, higher Injury Severity Scores, or craniotomy were generally more likely to have WLST. Withdrawal of LST was more likely for patients with functionally dependent health status (

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Background/Objective: Severe acute brain injury (SABI) is responsible for 12 million deaths annually, prolonged disability in survivors, and substantial resource utilization. Little guidance exists regarding indication or optimal timing of tracheostomy after SABI. Our aims were to determine national trends in tracheostomy utilization among mechanically ventilated patients with SABI in the USA, as well as to examine factors associated with tracheostomy utilization following SABI. Methods:We conducted a population-based retrospective cohort study using the National Inpatient Sample from 2002 to 2011. We identified adult patients with SABI, defined as a primary diagnosis of stroke, traumatic brain injury or post-cardiac arrest who received mechanical ventilation for greater than 96 h. We analyzed trends in tracheostomy utilization over time and used multilevel mixed-effects logistic regression to analyze factors associated with tracheostomy utilization.Results: There were 94,082 hospitalizations for SABI during the study period, with 30,455 (32%) resulting in tracheostomy utilization. The proportion of patients with SABI who received a tracheostomy increased during the study period, from 28.0% in 2002 to 32.1% in 2011 (p < 0.001). Variation in tracheostomy utilization was noted based on patient and facility characteristics, including higher odds of tracheostomy in large hospitals (OR 1.34, 95% CI 1.18-1.53, p < 0.001, compared to small hospitals), teaching hospitals (OR 1.15, 95% CI 1.06-1.25, p = 0.001, compared to nonteaching hospitals), and urban hospitals (OR 1.60, 95% CI 1.33-1.92, p < 0.001, compared to rural hospitals). Conclusions:Tracheostomy utilization has increased in the USA among patients with SABI, with wide variation by patient and facility-level factors.

Pituitary adenomas and Rathke's cleft cysts (RCCs) share a common embryological origin. Occasionally, these two lesions can present within the same patient. We present a case of a 39-year-old male who was found to have a large sellar lesion after complaints of persistent headaches and horizontal nystagmus. Surgical resection revealed components of a RCC co-existing with a pituitary adenoma. A brief review of the literature was performed revealing 38 cases of co-existing Rathke's cleft cysts and pituitary adenomas. Among the cases, the most common symptoms included headache and visual changes. Rathke's cleft cysts and pituitary adenomas are rarely found to co-exist, despite having common embryological origins. We review the existing literature, discuss the common embryology to these two lesions and describe a unique case from our institution of a co-existing Rathke's cleft cyst and pituitary adenoma.

Patients with traumatic brain injury (TBI) are at risk for extra-cranial complications, such as the acute respiratory distress syndrome (ARDS). We conducted an analysis of risk factors, mortality, and healthcare utilization associated with ARDS following isolated severe TBI. The National Trauma Data Bank (NTDB) dataset files from 2007-2014 were used to identify adult patients who suffered isolated [other body region-specific Abbreviated Injury Scale (AIS) < 3] severe TBI [admission total Glasgow Coma Scale (GCS) from 3 to 8 and head region-specific AIS >3]. In-hospital mortality was compared between patients who developed ARDS and those who did not. Utilization of healthcare resources (ICU length of stay, hospital length of stay, duration of mechanical ventilation, and frequency of tracheostomy and gastrostomy tube placement) was also examined. This retrospective cohort study included 38,213 patients with an overall ARDS occurrence of 7.5%. Younger age, admission tachycardia, pre-existing vascular and respiratory diseases, and pneumonia were associated with the development of ARDS. Compared to patients without ARDS, patients that developed ARDS experienced increased in-hospital mortality (OR 1.13, 95% CI 1.01-1.26), length of stay (p = <0.001), duration of mechanical ventilation (p = < 0.001), and placement of tracheostomy (OR 2.70, 95% CI 2.34-3.13) and gastrostomy (OR 2.42, 95% CI 2.06-2.84). After isolated severe TBI, ARDS is associated with increased mortality and healthcare utilization. Future studies should focus on both prevention and management strategies specific to TBI-associated ARDS.

OBJECTIVES: Traumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ dysfunction syndrome in traumatic brain injury is poorly understood. We examined the incidence and impact of early multiple organ dysfunction syndrome on clinical, functional, and disability outcomes over the year following traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: Patients enrolled in the Transforming Clinical Research and Knowledge in Traumatic Brain Injury study, an 18-center prospective cohort study of traumatic brain injury patients evaluated in participating level 1 trauma centers. SUBJECTS: Adult (age > 17 yr) patients with moderate-severe traumatic brain injury (Glasgow Coma Scale < 13). We excluded patients with major extracranial injury (Abbreviated Injury Scale score ≥ 3). INTERVENTIONS: Development of early multiple organ dysfunction syndrome, defined as a maximum modified Sequential Organ Failure Assessment score greater than 7 during the initial 72 hours following admission. MEASUREMENTS AND MAIN RESULTS: The main outcomes were: hospital mortality, length of stay, 6-month functional and disability domains (Glasgow Outcome Scale-Extended and Disability Rating Scale), and 1-year mortality. Secondary outcomes included: ICU length of stay, 3-month Glasgow Outcome Scale-Extended, 3-month Disability Rating Scale, 1-year Glasgow Outcome Scale-Extended, and 1-year Disability Rating Scale. We examined 373 subjects with moderate-severe traumatic brain injury. The mean (sd) Glasgow Coma Scale in the emergency department was 5.8 (3.2), with 280 subjects (75%) classified as severe traumatic brain injury (Glasgow Coma Scale 3–8). Among subjects with moderate-severe traumatic brain injury, 252 (68%) developed early multiple organ dysfunction syndrome. Subjects that developed early multiple organ dysfunction syndrome had a 75% decreased odds of a favorable outcome (Glasgow Outcome Scale-Extended 5–8) at 6 months (adjusted odds ratio, 0.25; 95% CI, 0.12–0.51) and increased disability (higher Disability Rating Scale score) at 6 months (adjusted mean difference, 2.04; 95% CI, 0.92–3.17). Subjects that developed early multiple organ dysfunction syndrome experienced an increased hospital length of stay (adjusted mean difference, 11.4 d; 95% CI, 7.1–15.8), with a nonsignificantly decreased survival to hospital discharge (odds ratio, 0.47; 95% CI, 0.18–1.2). CONCLUSIONS: Early multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.