Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE).

OBJECTIVE: Develop and validate a prognostic model for clinical deterioration or death within days of pulmonary embolism (PE) diagnosis using point-of-care criteria. METHODS: We used prospective registry data from six emergency departments. The primary composite outcome was death or deterioration (respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension, and rescue reperfusion intervention) within 5 days. Candidate predictors included laboratory and imaging right ventricle (RV) assessments. The prognostic model was developed from 935 PE patients. Univariable analysis of 138 candidate variables was followed by penalized and standard logistic regression on 26 retained variables, and then tested with a validation database (N = 801). RESULTS: Logistic regression yielded a nine-variable model, then simplified to a nine-point tool (PE-SCORE): one point each for abnormal RV by echocardiography, abnormal RV by computed tomography, systolic blood pressure < 100 mmHg, dysrhythmia, suspected/confirmed systemic infection, syncope, medico-social admission reason, abnormal heart rate, and two points for creatinine greater than 2.0 mg/dL. In the development database, 22.4% had the primary outcome. Prognostic accuracy of logistic regression model versus PE-SCORE model: 0.83 (0.80, 0.86) vs. 0.78 (0.75, 0.82) using area under the curve (AUC) and 0.61 (0.57, 0.64) vs. 0.50 (0.39, 0.60) using precision-recall curve (AUCpr). In the validation database, 26.6% had the primary outcome. PE-SCORE had AUC 0.77 (0.73, 0.81) and AUCpr 0.63 (0.43, 0.81). As points increased, outcome proportions increased: a score of zero had 2% outcome, whereas scores of six and above had ≥ 69.6% outcomes. In the validation dataset, PE-SCORE zero had 8% outcome [no deaths], whereas all patients with PE-SCORE of six and above had the primary outcome. CONCLUSIONS: PE-SCORE model identifies PE patients at low- and high-risk for deterioration and may help guide decisions about early outpatient management versus need for hospital-based monitoring.

Nutrition education for cardiovascular disease prevention in individuals with spinal cord injuries: study protocol for a randomized controlled trial.

BACKGROUND: Individuals with chronic spinal cord injuries (SCIs) have an increased prevalence of cardiovascular disease (CVD) and associated risk factors compared with age-matched control subjects. Exercise has been shown to improve selected CVD risk factors in individuals with SCI, but using nutrition education as an intervention has not been evaluated in this population. This paper describes our research plan for evaluating the effect of nutrition education on individuals with SCI. In the present study, called Eat Smart, Live Better, we are using a randomized controlled design to test an intervention adapted from an existing evidence-based program that showed a positive effect on nutrition knowledge and behavior of older adults from the general population. There will be an inpatient group (n = 100) and a community group (n = 100). The aims of our study are to compare the intervention and control groups for (1) changes in nutritional behavior, nutritional knowledge, and dietary quality by participants in the program; (2) levels of adiposity and metabolic CVD risk factors at 12-month follow-up; and (3) differential effects among individuals with SCI in the acute rehabilitation setting and those living in the community. METHODS/DESIGN: This is a randomized controlled trial of nutrition education. The treatment groups receive six nutrition education sessions. The control groups receive the one "standard of care" nutrition lecture that is required by the Commission on Accreditation of Rehabilitation Facilities. Treatment groups include both an inpatient group, comprising patients who have been admitted to an acute rehabilitation facility because of their recent SCI, and an outpatient group, consisting of community-dwelling adults who are at least 1 year after their SCI. A total of 200 participants will be randomized 1:1 to the intervention or control group, stratified by location (acute rehabilitation facility or community dwelling). DISCUSSION: To our knowledge, this will be the first reported study of nutrition education in individuals with SCI. The low cost and feasibility of the intervention, if shown to improve nutritional behavior, suggests that it could be implemented in rehabilitation facilities across the country. This has the potential of lowering the burden of CVD and CVD risk factors in this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02368405 . Registered on February 10, 2015.

The association between fatty acid index and in vitro fertilization outcomes.

PURPOSE: Fatty acids have been shown to play an important role in oocyte competence and early implantation of the embryo. Our hypothesis-generating study sought to determine if individual fatty acids expressed as a percentage of total erythrocyte fatty acids are associated with embryo quality and other in vitro fertilization (IVF) outcomes. METHODS: This was a prospective cohort study at an academic fertility center. Sixty women undergoing their first IVF cycle were recruited. Serum measurements of 22 fatty acids were obtained. We calculated each fatty acid as a percentage of total fatty acids, defined as the index for that individual fatty acid. RESULTS: Omega-3 index had no correlation with IVF outcomes. A negative correlation was found between the trans fatty acid index, elaidic acid (EA), and IVF outcomes, including fertilization rate (r = - 0.261, p = 0.04), blastocyst conversion rate (r = - 0.41, p = 0.001), and number of usable blastocysts and embryos (r = - 0.411, p = 0.001). There was no correlation between EA index and number of oocytes retrieved, embryo grade, or clinical pregnancy. No consistent correlations were observed with the additional fatty acids analyzed. CONCLUSIONS: No correlation was observed between omega-3 index and IVF outcomes. Elevated erythrocyte EA index, the major trans fatty acid commonly consumed in hydrogenated oils, margarine, and fried foods, was negatively correlated with number of usable blastocysts and embryos, blastocyst conversion, and fertilization rate. Our findings suggest preliminary evidence that trans fat may be negatively associated with IVF outcomes.

Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2 Diabetes on Metformin Monotherapy.

PURPOSE: Our aim was to determine the extent of clinical inertia and the associated patient and provider factors in patients with type 2 diabetes on metformin monotherapy (MM) at a large integrated health care system in the United States. METHODS: The study cohort included patients with type 2 diabetes aged 18 to 85 years, on MM between January 2009 and September 2013, who experienced MM failure (had an uncontrolled glycosylated hemoglobin [HbA1c] reading (≥8.0% [64 mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence of treatment intensification with an add-on therapy within 180 days after the MM failure (index date). The impact of patient and provider factors on clinical inertia was determined using generalized estimating equations. FINDINGS: The study cohort consisted of 996 patients; 58% were men and 59% were white, with a mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower HbA1c at index date, absence of liver diseases, absence of renal diseases, and greater provider age were associated with clinical inertia. The clinical inertia rate in a secondary analysis considering HbA1c <7.0% (53 mmol/mol) as glycemic control was 67.9%. Greater patient age, lower HbA1c at index date, greater provider age, and being a primary care physician were associated with clinical inertia. IMPLICATIONS: Considerable clinical inertia rates were observed in our real-world patient population, suggesting the need of interventions to reduce clinical inertia in clinical practice. Information about patient and provider factors affecting clinical inertia provided by this study could help healthcare policymakers plan and implement such interventions.

Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study.

STUDY DESIGN: Cadaveric model. OBJECTIVES: To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. METHODS: A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. RESULTS: The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. CONCLUSION: The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. LEVEL OF EVIDENCE: N/A.

Interobserver and Intraobserver Agreement on Qualitative Assessments of Right Ventricular Dysfunction With Echocardiography in Patients With Pulmonary Embolism.

OBJECTIVES: To evaluate observer agreement using qualitative goal-directed echocardiographic criteria for right ventricular (RV) dysfunction prognostication in submassive pulmonary embolism (PE). METHODS: Two emergency physicians and 2 cardiologists independently reviewed 31 packets of goal-directed echocardiographic video clips consisting of at least 3 windows obtained by emergency physicians from normotensive patients with PE. Nine packets were repeated to assess for intraobserver agreement. Right ventricular dysfunction criteria on goal-directed echocardiography were as follows: RV enlargement was present, with a right-to-left ventricular basal diameter ratio of 1.0 or higher and blunting of the apex of the RV in 2 or more different windows; RV systolic dysfunction was present if the tricuspid annulus moved toward the apex 10 mm or less and there was RV free wall hypokinesis; and septal deviation was present with any flattening or deviation of the ventricular septum toward the left ventricle. RESULTS: Among the 4 participants, there was 83.9% agreement on the presence or absence of RV enlargement (κ = 0.84), 74.2% agreement on the presence or absence of RV systolic dysfunction (κ = 0.69), and 71.0% agreement on the presence or absence of septal deviation (κ = 0.59). Intraobserver agreement was 100% for each RV dysfunction variable for each observer (κ = 1.0). CONCLUSIONS: Agreement was substantial for both severe RV enlargement and RV systolic dysfunction and moderate for septal deviation. Right ventricular dysfunction assessment with qualitative goal-directed echocardiographic criteria is reproducible for PE risk stratification.

Human annulus signaling cues for nerve outgrowth: In vitro studies.

The relationship between neurotrophins produced by human annulus cells, such as neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) which function in neurite survival and outgrowth, and nerve ingrowth into the disc remains poorly understood. In this work, we tested F11 neurite growth during exposure to control media, media with added nerve growth factor (NGF), conditioned media (CM) harvested from previous human annulus culture, or co-culture with annulus cells. Co-culture of F11 cells with annulus cells significantly increased media levels of amphiregulin, BDNF, glial-derived neurotrophic factor, and vascular endothelial growth factor compared to levels from in culture of F11 cells alone (p ≤ 0.04). Cell-based assays of neurite growth revealed that BDNF levels present in CM bore a significant (p = 0.01) positive relationship to neurite length and accounted for 38.5% of the change in neurite length. NT4 levels produced during co-culture with annulus cells bore a significant (p = 0.04) positive relationship to neurite length and accounted for 40.9% of the change in length. Statement of clinical significance: In vitro findings point to a potential role of annulus cells related to nerve ingrowth in vivo, and may have relevance in the outer annulus (where cell numbers are high) or in regions where nerves penetrate into annular tears or fissures. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1456-1465, 2016.

Diagnostic Accuracy of Right Ventricular Dysfunction Markers in Normotensive Emergency Department Patients With Acute Pulmonary Embolism.

STUDY OBJECTIVE: We determine the diagnostic accuracy of goal-directed echocardiography, cardiac biomarkers, and computed tomography (CT) in early identification of severe right ventricular dysfunction in normotensive emergency department patients with pulmonary embolism compared with comprehensive echocardiography. METHODS: This was a prospective observational study of consecutive normotensive patients with confirmed pulmonary embolism. Investigators, blinded to clot burden and biomarkers, performed qualitative goal-directed echocardiography for right ventricular dysfunction: right ventricular enlargement (diameter greater than or equal to that of the left ventricle), severe right ventricular systolic dysfunction, and septal bowing. Brain natriuretic peptide and troponin cutoffs of greater than or equal to 90 pg/mL and greater than or equal to 0.07 ng/mL and CT right ventricular:left ventricular diameter ratio greater than or equal to 1.0 were also compared with comprehensive echocardiography. RESULTS: One hundred sixteen normotensive pulmonary embolism patients (111 confirmed by CT, 5 by ventilation-perfusion scan) were enrolled. Twenty-six of 116 patients (22%) had right ventricular dysfunction on comprehensive echocardiography. Goal-directed echocardiography had a sensitivity of 100% (95% confidence interval [CI] 87% to 100%), specificity of 99% (95% CI 94% to 100%), positive likelihood ratio (+LR) of 90.0 (95% CI 16.3 to 499.8), and negative likelihood ratio (-LR) of 0 (95% CI 0 to 0.13). Brain natriuretic peptide had a sensitivity of 88% (95% CI 70% to 98%), specificity of 68% (95% CI 57% to 78%), +LR of 2.8 (95% CI 2.0 to 3.9), and -LR of 0.17 (95% CI 0.06 to 0.43). Troponin had a sensitivity of 62% (95% CI 41% to 80%), specificity of 93% (95% CI 86% to 98%), +LR of 9.2 (95% CI 4.1 to 20.9), and -LR of 0.41 (95% CI 0.24 to 0.62). CT had a sensitivity of 91% (95% CI 72% to 99%), specificity of 79% (95% CI 69% to 87%), +LR of 4.3 (95% CI 2.8 to 6.7), and -LR of 0.11 (95% CI 0.03 to 0.34). CONCLUSION: Goal-directed echocardiography was highly accurate for early severe right ventricular dysfunction identification and pulmonary embolism risk-stratification. Brain natriuretic peptide was sensitive but less specific, whereas troponin had lower sensitivity but higher specificity. CT had good sensitivity and moderate specificity.

Early neurologic examination is not reliable for prognostication in post-cardiac arrest patients who undergo therapeutic hypothermia.

BACKGROUND: Recent advances in post-cardiac arrest (CA) care including therapeutic hypothermia (TH) have improved survival and favorable neurologic outcomes for survivors of CA. Survivors often present with deep coma and lack of brainstem reflexes, which are generally associated with adverse outcomes in many disease processes. Little is known regarding the role of initial emergency department (ED) neurological examination and its potential for prognostication. OBJECTIVES: The purpose of this study is to determine if components of a standardized neurologic examination are reliable prognosticators in patients recently resuscitated from CA. We hypothesize that lack of neurologic function does not reliably predict an adverse outcome and, therefore, should not be used to determine eligibility for TH. METHODS: A standardized neurologic examination was performed in the ED on a prospective, convenience cohort of post-CA patients presenting to a CA resuscitation center who would undergo a comprehensive postarrest care pathway that included TH. Data such as prior sedation or active neuromuscular blockade were documented to evaluate for the presence of possible confounders. Examination findings were then compared with hospital survival and neurologic outcome at discharge as defined by the cerebral performance category (CPC) score as documented in the institutional TH registry. RESULTS: Forty-nine subjects were enrolled, most of whom presented comatose with a Glasgow Coma Scale of 3 (n=41, 83.7%). Nineteen subjects (38.8%) had absence of all examination findings, of which 4 of 19 (21.1%) survived to hospital discharge. Of those with at least 1 positive examination finding, 13 of 30 subjects (43.3%) survived to hospital discharge. Subgroup analysis showed that 9 of the 19 patients with absence of brainstem reflexes did not have evidence of active neuromuscular blockade at the time of the examination; 2 of 9 (22.1%) survived to hospital discharge. Eight of these subjects in this group had not received any prior sedation; 1 of 8 (12.5%) survived to hospital discharge. Only 1 of the 17 subjects who survived was discharged with poor neurologic function with a CPC score=3, whereas all others who survived had good neurologic function, CPC score=1. CONCLUSION: In this cohort of patients treated in a comprehensive postarrest care pathway that included TH, absence of neurologic function on initial ED presentation was not reliable for prognostication. Given these findings, clinicians should refrain from using the initial ED neurological examination to guide the aggressiveness of care or in counseling of family members regarding anticipated outcome.

Increased Anesthesia Usage in a Large-Volume Endoscopy Unit: Patient Acuity Is Not the Main Predictor.

OBJECTIVES: The use of monitored anesthesia care (MAC) for colonoscopy sedation continues to increase. This study examined trends during a 9-year period in the use of MAC and explored which patient variables may have influenced these trends. METHODS: This was a retrospective review of all colonoscopies performed in our hospital-based endoscopy unit from 2003 through 2012. We determined whether MAC was used and if not, which quantitative doses of sedative agents were used. Several patient-related variables were evaluated for correlation. Data were analyzed (t test, χ(2), logistic regression) using SAS statistical software. RESULTS: Between January 2003 and October 2012, we identified 37,803 performed colonoscopies. The use of MAC increased significantly, from 0.38% in 2003 to 10.0% in 2012 (P < 0.0001). For cases in which conscious sedation was used, the mean doses of sedatives did not change significantly over time. Although there was an association between certain patient variables (female sex; higher American Society of Anesthesiologists class; diagnostic procedures; and pulmonary, psychiatric, renal or cerebrovascular diseases) and the use of MAC, the greatest predictor of MAC use was the year of the procedure. After adjusting for the patient variables that were examined, the odds of using MAC increased by approximately 1.5 times per year from 2003 through 2012. The adjusted odds of using MAC in 2012 were 35.8 times higher than in 2003. CONCLUSIONS: The use of MAC for colonoscopies performed in our endoscopy unit increased significantly from 2003 to 2012. Although increased MAC use was associated with some patient variables, it was most significantly associated with the year of the procedure. This suggests that there were other nonpatient-related factors influencing its use.

Validation of a Screening Tool to Identify Undernutrition in Ambulatory Patients With Liver Cirrhosis.

BACKGROUND: The prevalence of chronic liver disease is increasing in the United States. Malnutrition is common as liver disease progresses. However, an accepted method to screen these patients for malnutrition is lacking. The 6-question undernutrition screening tool was developed for professionals without nutrition training to identify a decline in the nutrition status of patients with liver cirrhosis. A 3-phase validation study was completed to assess face, content, and clinical validity of the screening tool in ambulatory patients with liver cirrhosis. METHODS: In phase I, face validity was determined by surveying 13 liver disease professionals. In phase II, content validity was assessed by surveying 12 registered dietitians who specialize in liver disease. In phase III, a cross-sectional investigation was completed to compare the agreement between the undernutrition screening tool and nutrition assessment by a registered dietitian (RD). RESULTS: Twenty-two patients with a diagnosis of liver cirrhosis participated in phase III of the investigation. The RD assessment identified undernutrition in 82% of patients (95% CI, 60%-95%). The κ statistic indicated a fair agreement between the screening tool and RD assessment. Sensitivity and specificity of the tool were 72% and 75%, respectively, and positive predictive value was 93%. CONCLUSIONS: Feedback from phase I, II, and III indicate that the undernutrition screening tool is simple, is easy to use, and measures the constructs that have the strongest link with undernutrition in liver disease. Additional minor adjustments to the screening tool and a multicenter investigation are indicated to confirm clinical effectiveness and cross-validity of the tool.

BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial.

Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.

Reliability of the timed 10-metre walk test during inpatient rehabilitation in ambulatory adults with traumatic brain injury.

OBJECTIVE: To determine the test-re-test reliability of the timed 10-metre walk test (10MWT) among adults with traumatic brain injury (TBI) enrolled in inpatient rehabilitation. DESIGN: Prospective reliability study using a correlational design. SETTING: Inpatient rehabilitation unit of a rehabilitation hospital. PARTICIPANTS: Twenty-three consecutive adults with acute TBI, mean age = 35.87, SD = 14.2 years (range = 18-64 years). This study tested 22 males and one female, who were 15.6 (SD = 9.1) days in inpatient rehabilitation at time of gait testing. METHOD: Repeated, timed 10-metre gait test within a 1-hour testing period with six trials at self-selected pace (SSP) and six trials at fastest pace (FP), recorded to the nearest 1/10 second with a hand-held stopwatch. RESULT: Gait speed measurements for SSP and FP were shown to have excellent test-re-test reliability (Intra Class Correlation coefficient = 0.964 and 0.961, respectively). CONCLUSIONS: These results add to the literature that the timed 10MWT is a reliable measure of gait velocity in adults with acute TBI for both FP and SSP.

Vestibular deficits leading to disequilibrium and falls in ambulatory amyotrophic lateral sclerosis.

OBJECTIVE: To assess vestibular deficits in response to disequilibrium in ambulatory individuals with amyotrophic lateral sclerosis (ambALS). DESIGN: All participants completed standard protocols for the Sensory Organization Test (SOT) by computerized dynamic posturography. SETTING: Multidisciplinary amyotrophic lateral sclerosis clinic at an academic medical center. PARTICIPANTS: Study participants (N=34) consisted of ambALS (n=19) and healthy controls (HC) (n=15). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Equilibrium scores (ESs) obtained from averaged sway amplitude in condition 5 (ES5) and condition 6 (ES6) of the SOT. RESULTS: In conditions of altered somatosensory information with vision absent or vision sway-referenced, the mean ± SD scores for ambALS (ES5=51.4±22.5; ES6=50.8±22.1) were lower than those for HC (ES5=65.4±11.7, P≤.03; ES6=58.9±12.5, P>.05). Seven ambALS (37%) experienced a total of 19 falls during the sway-referenced support test conditions. There were no falls in the HC. CONCLUSIONS: Nearly 37% of ambALS with normal clinical balance testing have decreased ability to use the vestibular input and required increased reliance on visual input for postural orientation to sustain equilibrium. The mechanism of this alteration in sensory preference is not completely clear. Extrapyramidal involvement early in ALS may be indicated.

Dietary intake and adherence to the 2010 Dietary Guidelines for Americans among individuals with chronic spinal cord injury: a pilot study.

OBJECTIVE: To investigate dietary intake and adherence to the 2010 Dietary Guidelines for Americans in individuals with chronic spinal cord injury (SCI) and able-bodied individuals. DESIGN: A pilot study of dietary intake among a sample of individuals with SCI >1 year ago from a single site compared with able-bodied individuals. PARTICIPANTS/METHODS: One hundred black or white adults aged 38-55 years old with SCI >1 year and 100 age-, sex-, and race-matched adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake was assessed by the CARDIA dietary history. Linear regression analysis was used to compare dietary intake between the subjects with SCI and those enrolled in the CARDIA study. Further, adherence to the 2010 Dietary Guidelines for dairy, fruits, and vegetables, and whole-grain foods was assessed. RESULTS: Compared with CARDIA participants, participants with SCI consumed fewer daily servings of dairy (2.10 vs. 5.0, P < 0.001), fruit (2.01 vs. 3.64, P = 0.002), and whole grain foods (1.20 vs. 2.44 P = 0.007). For each food group, fewer participants with SCI met the recommended servings compared with the CARDIA participants. Specifically, the participants with SCI and in CARDIA who met the guidelines were, respectively: dairy, 22% vs. 54% (P < 0.001), fruits and vegetables 39% vs. 70% (P = 0.001), and whole-grain foods 8% vs. 69.6% (P = 0.001). CONCLUSIONS: Compared with able-bodied individuals, SCI participants consumed fewer daily servings of fruit, dairy, and whole grain foods than proposed by the 2010 Dietary Guideline recommendations. Nutrition education for this population may be warranted.

A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence.

PURPOSE: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. METHODS AND MATERIALS: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. RESULTS: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. CONCLUSIONS: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial.

Spontaneous age-related cervical disc degeneration in the sand rat.

BACKGROUND: Disc space narrowing, osteophytes, and disc degeneration are common and increase with aging. Few animal models are appropriate for the study of spontaneous age-related cervical disc degeneration. QUESTIONS/PURPOSES: We used the sand rat, a member of the gerbil family with well-recognized age-related lumbar disc degeneration, to determine whether spontaneous cervical disc degeneration differed from lumbar degeneration when evaluated by (1) radiologic and (2) histologic measures. Animals 2 to 25 months of age were used in these analyses. METHODS: Cervical and lumbar discs of 99 sand rats were analyzed with radiology, and cervical discs of 67 sand rats were studied with histology. Lateral digital radiographs of cervical and lumbar spines were scored for presence or absence of wedging, disc space narrowing, osteophytes, end plate calcification, and irregular disc margins at C2-C3 through C6-C7 and T12-L1 through L7-S1. Percentages for presence were calculated and statistically analyzed for younger (range, 2-11.9 months old) versus older (range, 12.0-25 months old) animals. RESULTS: Cervical discs in younger animals exhibited a greater proportion of irregular margins compared with lumbar sites (94% versus 83%; p = 0.02; 95% CI for difference, 2.7, 19.0%). In older animals, cervical discs showed a greater proportion of osteophytes than did lumbar discs (7% versus 0%; p < 0.0001). The incidence of disc space narrowing was greater in cervical versus lumbar sites (99% versus 90%; p = 0.0008). Cervical spine sites which contained osteophytes morphologically showed irregular disc margins and revealed an extrusion of herniated disc material in the osteophytes. CONCLUSIONS: Radiologic and morphologic studies confirmed age-related disc degeneration in the cervical spine of the sand rat. CLINICAL RELEVANCE: Clinical cervical aging studies have shown that 14% of asymptomatic subjects younger than 40 years have abnormal MRI scans with an increase to 50% by 50 years old. We studied an economic rodent model for cervical age-related spontaneous disc.

Central vascular catheter placement evaluation using saline flush and bedside echocardiography.

OBJECTIVES: Central venous catheter (CVC) placement is a common procedure in critical care management. The authors set out to determine echocardiographic features during a saline flush of any type of CVC. The hypothesis was that the presence of a rapid saline swirl in the right atrium on bedside echocardiography would confirm correct placement of the CVC tip, similar to the accuracy of the postplacement chest radiograph (CXR). METHODS: This was a prospective convenience sample of emergency department (ED) and intensive care unit (ICU) patients who had CVCs placed. Investigators used subcostal or apical four-chamber echocardiography windows to evaluate the onset and appearance of turbulent flow in the right atrium when the distal port of the CVC was flushed with 10 mL of saline. Onset was rated as "immediate" (within 2 seconds), "delayed" (2 to 6 seconds), or "absent" (did not appear within 6 seconds). Appearance was rated as "prominent," "speckling," or "absent." Digital video review was used later to objectively determine precise timing of turbulence onset. The rapid atrial swirl sign (RASS) was defined as the echo appearance of turbulence entering the right atrium immediately (within 2 seconds) after the saline flush of the CVC distal port. The observance of RASS ("positive") was considered "negative" for CVC malposition. Echocardiographic results were compared to CVC tip locations within predetermined zones on the CXR. Superior vena cava (SVC) region was considered the optimal CVC tip position for subclavian and internal jugular CVC. Left CVC tips within the mid left innominate vein were also considered appropriately placed. RESULTS: A total of 142 patients enrolled, yielding 152 CVCs. Two CVCs were excluded from analysis due to incomplete data. Both CXR and echocardiographic images for 107 internal jugular CVCs and 28 subclavian CVCs were available for analysis. Saline flush echo evaluations were also performed on 15 femoral CVCs. Either 16-cm triple-lumen or 20-cm PreSep CVCs were used. CVC malposition was discovered on CXR in four of 135 (3.0%) of the subclavian and internal jugular CVCs. RASS for subclavian and internal jugular CVC evaluations versus CXR results for CVC tip malposition yielded 75% sensitivity, 100% specificity, positive predictive value (PPV) 100% (95% confidence interval [CI] = 29.24% to 100%), and negative predictive value (NPV) 99.24% (95% CI = 95.85% to 99.98%). Mean (±SD) time for onset of saline flush turbulence was 1.1 (±0.3) seconds for subclavian and internal jugular CVC tips within the target CXR zone. CONCLUSIONS: The rapid appearance of prominent turbulence in the right atrium on echocardiography after CVC saline flush serves as a precise bedside screening test of optimal CVC tip position.

Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-ß and TNF-α in 3D culture.

Chemokines act as important secondary inflammatory mediators which are released by cells in response to a variety of stimuli. Chemokines bind to cell surface receptors and act as second-order cytokines with specialized functions in inflammation. The role of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) (also called CCL5 (chemokine (C-C motif) ligand 5)) has received little attention to date in disc tissue. Microarray analyses of lumbar disc annulus tissue revealed that RANTES expression was significantly upregulated in more degenerated Thompson grades IV and V discs compared to expression levels in grades I, II and III discs (p=0.032). Immunolocalization confirmed the presence of RANTES in the annulus and nucleus of the disc, and localized the RANTES receptors CCR1, CCR3 and CCR5 to cells in the disc. In vitro studies with IL-1-ß and TNF-α challenges, both proinflammatory cytokines resulted in elevated levels of RANTES in conditioned media (p<0.01); TNF-α exposure, however, produced significantly greater levels than did IL-1alpha (p<0.0001), suggesting a differential regulation by TNF-α. Local production of RANTES in vivo by annulus and nucleus cells, and in vitro induction of RANTES by proinflammatory cytokines suggest that disc cells are primary effector cells as well as target cells, and thus can mediate physiological immune-related processes during disc degeneration by both autocrine and paracrine signaling.