Citations

AbstractMammographic percent density (PD) is a strong risk factor for breast cancer, but there has been relatively little systematic evaluation of other features in mammographic images that might additionally predict breast cancer risk. We evaluated the association of a large number of image texture features with risk of breast cancer using a clinic-based case-control study of digitized film mammograms, all with screening mammograms before breast cancer diagnosis. The sample was split into training (123 cases and 258 controls) and validation (123 cases and 264 controls) data sets. Age-adjusted and body mass index (BMI)–adjusted odds ratios (OR) per SD change in the feature, 95% confidence intervals, and the area under the receiver operator characteristic curve (AUC) were obtained using logistic regression. A bootstrap approach was used to identify the strongest features in the training data set, and results for features that validated in the second half of the sample were reported using the full data set. The mean age at mammography was 64.0 ± 10.2 years, and the mean time from mammography to breast cancer was 3.7 ± 1.0 (range, 2.0-5.9 years). PD was associated with breast cancer risk (OR, 1.49; 95% confidence interval, 1.25-1.78). The strongest features that validated from each of several classes (Markovian, run length, Laws, wavelet, and Fourier) showed similar ORs as PD and predicted breast cancer at a similar magnitude (AUC = 0.58-0.60) as PD (AUC = 0.58). All of these features were automatically calculated (unlike PD) and measure texture at a coarse scale. These features were moderately correlated with PD (r = 0.39-0.76), and after adjustment for PD, each of the features attenuated only slightly and retained statistical significance. However, simultaneous inclusion of these features in a model with PD did not significantly improve the ability to predict breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):837–45)

Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

Abstract The maturation of naive CD8+ T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8+ effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.

ABSTRACTObjective:To describe the relationships between gastric emptying, autonomic function, and postural tachycardia in adolescent patients with nausea and/or abdominal discomfort. It was hypothesized that patients with both gastrointestinal symptoms and symptoms of orthostatic intolerance are more likely to show abnormal tilt table results and delayed gastric emptying.Patients and Methods:A retrospective review was conducted of adolescent patients who came to a pediatric referral center because of nausea and dyspepsia and who subsequently underwent both autonomic reflex screening and gastric emptying testing. Patients with a heart rate change of 30 or more beats per minute on the heads‐up tilt table test were assigned to the postural orthostatic tachycardia syndrome (POTS) group (n = 21), and those with a heart rate change of fewer than 30 beats per minute on the heads‐up tilt table test were assigned to the non‐POTS group (n = 10).Results:There was no significant difference between the POTS and non‐POTS groups with regard to presenting symptoms (P > 0.05). Overall, 13 (42%) individuals had abnormal gastric emptying results (delayed in 6, accelerated in 7), but gastric emptying scores were similar between the POTS and non‐POTS groups. Furthermore, there was no correlation between an individual's gastric emptying results at 1, 2, and 4 hours and that person's heart rate change on HUT (r = −0.05, −0.15, and −0.19).Conclusions:Although altered gastric emptying and postural tachycardia are common in a referral population of adolescents with nausea and/or abdominal discomfort, the clinical presentation was not predictive of test results. Furthermore, delayed gastric emptying was not correlated with the current definition of postural tachycardia.

Background Paraplegia is a devastating complication for patients undergoing repair of thoracoabdominal aortic aneurysms. A monitor to detect spinal cord ischemia is necessary if anesthesiologists are to intervene to protect the spinal cord during aortic aneurysm clamping. Methods The medical records of 60 patients who underwent thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling with evoked potential monitoring were reviewed. The authors analyzed latency and amplitude of motor evoked potentials, somatosensory evoked potentials, and H reflexes before cooling and clamping, after cooling and before clamping, during clamping, and after release of aortic cross clamp. Results Twenty minutes after the aortic cross clamp was placed, motor evoked potentials had 88% sensitivity and 65% specificity in predicting spinal cord ischemia. The negative predictive value of motor evoked potentials at 20 min after aortic cross clamping was 96%. Conclusions Rapid loss of motor evoked potentials or H reflexes after application of the aortic cross clamp identifies a subgroup of patients who are at high risk of developing spinal cord ischemia and in whom aggressive anesthetic and surgical interventions may be justified.

Background The authors determined associated cardiac arrest and death rates in cases from Canada and the United States as reported to The North American Malignant Hyperthermia (MH) Registry and analyzed factors associated with a higher risk of poor outcomes. Methods The authors searched the database for AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports with inclusion criteria as follows: event date between January 1, 1987, and December 31, 2006; "very likely" or "almost certain" MH as ranked by MH Clinical Grading Scale; location in Canada or the United States; and one or more anesthetic agents given. The exclusion criterion was a pathologic condition other than MH independently judged by the authors. Severe MH outcomes were analyzed as regards clinical history and presentation, using Wilcoxon rank sum tests for continuous variables and Pearson exact chi-square tests for categorical variables. A Bonferroni correction adjusted for multiple comparisons. Results Of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2-31 yr). Associated factors were muscular build (odds ratio, 18.7; P = 0.0016) and disseminated intravascular coagulation (odds ratio, 49.7; P < 0.0001). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide (216 vs. 87 min; P = 0.003). Unrelated factors included patient or family history, anesthetic management, and the MH episode. Conclusions Modern US anesthetic practice did not prevent MH-associated cardiac arrest and death in predominantly young, healthy patients undergoing low- to intermediate-risk surgical procedures.

Background Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33 degrees C) versus normothermia (temperature = 36.5 degrees C) in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Anesthesia was dictated by a limited-options protocol with the use of nitrous oxide determined by individual anesthesiologists. All patients were assessed daily for 14 days after surgery or until hospital discharge. Neurologic and neuropsychological testing were conducted at 3 months after surgery. Outcome data were analyzed via both univariate tests and multivariate logistic regression analysis correcting for factors thought to influence outcome. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. Results Outcome data were available for 1,000 patients, of which 373 received nitrous oxide. There was no difference between groups in the development of delayed ischemic neurologic deficit. At 3 months after surgery, there were no significant differences between groups in any outcome variable: Glasgow Outcome Score (OR, 0.84; 95% confidence interval [CI], 0.63-1.14; P = 0.268), National Institutes of Health Stroke Scale (OR, 1.29; 95% CI, 0.96-1.73; P = 0.087), Rankin Disability Score (OR, 0.84; 95% CI, 0.61-1.15; P = 0.284), Barthel Activities of Daily Living Index (OR, 1.01; 95% CI, 0.68-1.51; P = 0.961), or neuropsychological testing (OR, 1.26; 95% CI, 0.85-1.87; P = 0.252). Conclusions In a population of patients at risk for ischemic brain injury, nitrous oxide use had no overall beneficial or detrimental impact on neurologic or neuropsychological outcomes.