Related-samples Wilcoxon Signed-rank Test Research Articles

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions.

The impact of fever on corrected QT interval

AimsWe were interested in the impact of fever on the QT interval as information on this subject is limited. MethodsWe performed a retrospective, single centre study over a two year period, ending December 31st, 2013. Participants were identified using an electronic chart review of emergency department records linked to an ECG data base. Study subjects were drawn from patients presenting with fever to an academic emergency department in Canada. Our study identified febrile (T>38.0°C) patients aged >18years presenting to our centre. Included participants must have had an ED based ECG at the time of presentation with fever and a comparison ECG performed within 30days and without fever. Actively paced patients were excluded. QT values were corrected using Bazett's, Fridericia's and The Framingham Formula. QT values for febrile and afebrile cohorts were compared using Related-Samples Wilcoxon Signed Rank Test. Results181 patients satisfied our inclusion/exclusion criteria, 54.1% were female and mean age was 68.9years old. Mean duration between febrile and afebrile ECGs was 6.1days. The median corrected QT interval (QTc) was significantly shorter in patients during their febrile presentation, as compared to their afebrile presentation when correcting for QT using both Framingham [QTc=466.1ms (445.8–499.5) vs. 507.6 (476.0–539.0); p<0.001] and Fridericia's formula [QTc=388.7ms, (371.5–407.5) vs. 406.7ms, (386.1–434.4); p<0.001]. This difference was independent of gender. ConclusionWe found fever to shorten the QTc independently of sex in a general emergency department population.

Abstract B20: Peritumoral CD3+ lymphocyte infiltration at the brain-brain metastasis interface is detectable by diffusion MRI and independently associated with prolonged survival

Abstract Brain metastases are an increasing clinical problem, causing significant morbidity and mortality in patients with solid organ cancer. Diffusion along white matter tracts can be assessed by diffusion tensor MRI (DTI) and disruption of white matter tract integrity generally indicates tumor invasion and inflammation in the brain. Matched preoperative DTI and image-guided neurosurgical sampling of the brain-brain metastasis interface was performed in 26 adult patients undergoing resection of a brain metastasis, uniquely yielding paired MRI and biological data from the same regions. Patients were followed prospectively from imaging diagnosis until death. In this surgical series patients were mostly of excellent performance status with no or stable primary disease. We consistently observed dense, activated macrophage infiltration at the brain-brain metastasis interface across tumors from different primaries. CD20-positive, B cell infiltration was sparse (with no significant difference from control white matter). CD3-positive lymphocytes were seen in the peritumoral region in all except 1 case (median 16 cells per high power field (HPF), significantly greater than control white matter, p&amp;lt;0.001). Peritumoral density of these cells, but not edge or core density and not peritumoral macrophage or B-cell infiltration, was associated with prolonged survival, even when controlling for confounders such as adjuvant whole brain radiotherapy (Cox proportional hazards analysis, HR = 0.96, 95% CI 0.93-0.99, p=0.021). When this CD3-positive lymphocyte response was further categorized into three groups (&amp;lt;5, 5-25 and &amp;gt;25 immunoreactive cells/HPF), those with moderate peritumoral infiltration were at no survival advantage compared to those with low infiltration, whereas those with the highest infiltrates lived over twice as long (median 11.7 months, vs. 5.1 and 5.2 months for moderate and low groups respectively, log rank test=10.06, p=0.007). Using image analysis of the paired MRI data, average fractional anisotropy (FA) readings in the peritumoral region were significantly lower than the unaffected, contralateral hemisphere indicating white matter disruption (related samples Wilcoxon-signed rank test, p&amp;lt;0.001). Those patients with a lower peritumoral FA (below median), indicating more white matter tract disruption, showed longer survival (median 9.9 months, 95% CI: 7.4-12.4 versus 5.3 months, 95% CI: 3.4-7.1) even if confounding variables were accounted for (HR = 0.21, 95% CI 0.06-0.96, p=0.044). The peritumoral density of CD3-positive lymphocytes was the only significant biological difference observed between the cases with high and low peritumoral FA i.e. metastases with less or more white matter tract disruption around them (Mann Whitney U, p=0.037). There were no differences in the presence of other immunoreactive cells, primary cancer type, growth pattern (invasive or pseudo-encapsulated), expression of matrix-metallo-proteinases, cellularity, Ki67 proliferative index, vascularity, necrosis or connective tissue density at the leading edge of the tumor or adjacent peritumoral region in those metastases with lower as opposed to higher peritumoral FA readings. Overall this unique data suggests that the cellular immune response to brain metastases is robust, may be a marker of subsequent overall survival and can be assayed non-invasively by measuring white matter tract disruption at DTI. Citation Format: Rasheed Zakaria, Michael D. Jenkinson, Philip S. Rudland. Peritumoral CD3+ lymphocyte infiltration at the brain-brain metastasis interface is detectable by diffusion MRI and independently associated with prolonged survival. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B20.

Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases

BackgroundTumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first...

Association between tissue-inflammation biomarkers and progression of osteoarthritis: Evidence from the Rotterdam Study

cytokine concentrations at first (þ) and second (x) examinations with box plots summarizing the examinations using the timeline as x-axis. Boxes represent the median and quartiles, whiskers the 10 and 90 percentiles, and the box widths the relative sample sizes at the two examinations. Tables show median (25 and 75 percentiles) concentrations with p-values from related-samples Wilcoxon signed-rank test from comparAbstracts / Osteoarthritis and Cartilage 23 (2015) A26eA81 A50

Iterative Reconstruction for Head CT: Effects on Radiation Dose and Image Quality.

Iterative reconstruction has been reported to reduce radiation dose in CT, while preserving and even improving image quality. The purpose of this study was to evaluate the effects of sinogram-affirmed iterative reconstruction (SAFIRE) on radiation dose reduction and image quality for noncontrast adult head CT and to compare SAFIRE with conventional filtered back-projection (FBP) reconstruction. Institutional review board approval was obtained for this retrospective analysis of head CT scans reconstructed with SAFIRE and/or FBP for 107 patients. Radiation dose parameters were recorded from scanner-generated CT dose reports. Signal-to-noise and contrast-to-noise ratios (SNR, CNR) were calculated from gray and white matter (GM, WM) attenuation measurements. Image noise, artifacts, GM-WM differentiation, small structure visibility, and sharpness were graded by two readers. Statistical analysis included the independent-samples t test for quantitative data, the related samples Wilcoxon signed-rank test for qualitative data, the coefficient of repeatability for intraobserver variation, and κ statistics for interobserver agreement. Mean effective dose was significantly reduced with SAFIRE from 2.0 to 1.7 mSv (p<0.0001). SAFIRE also significantly improved GM SNR, WM SNR, and GM-WM CNR (p<0.0001). Significant reductions in image noise and posterior fossa artifact as well as improvements in GM-WM differentiation, small structure visibility, and sharpness were noted with SAFIRE (P<0.005). SAFIRE for noncontrast adult head CT reduces patient radiation dose by 15% for the settings employed at our institution, while significantly improving multiple quantitative and qualitative measures of image quality.

Board 404 - Research Abstract Evaluation of Simulation Education using Anesthesia Information System (Submission #99)

Introduction/Background The use of high-fidelity patient simulation is a validated educational tool for anesthesiology resident training, especially for novice residents.1 Simulation has the advantage of teaching students clinically applicable skills and judgment without risking patient harm. Documentation of improved speed with acquisition of technical skills, such as fiberoptic intubation2 and central line placement,3 has been published but very few studies have been able to demonstrate a correlation between high-fidelity simulation education and improvement in patient outcomes. Wayne et al4 have demonstrated that simulation-based education of internal medicine residents in ACLS and code blue training resulted in an improved adherence to ACLS protocols during actual hospital code blue events. Barsuk et al5 showed that resident simulation-based training can reduce catheter related blood stream infections. Aside from these few small studies, there is little data to substantiate the belief that simulation-based education Results in improved patient outcomes. This study examines the effect of simulation on the treatment of emergence of hypertension through the examination of EMR records. Methods IRB was obtained through UC Irvine Simulation Center. Participants were anesthesiology resident volunteers. Each resident participated in a simulation which contained a patient with hypertension at emergence. The simulation session included a 20 minute scenario participation followed by a 40 minute debriefing. Pharmacologic treatment of hypertension was reviewed during the debriefing. The simulation scenario was the same for each participant. Surgical Information Systems (SIS) is the Anesthesia Information Management System (AIMS) or electronic anesthesia medical record at UC Irvine Medical Center. The electronic anesthesia records of each participant were then searched for the cases one month prior to the simulation education sessions to evaluate whether or not hypertension at emergence was treated pharmacologically. Emergence was defined as within 30 minutes of extubation and hypertension was defined as mean arterial pressure (MAP) 20% greater than baseline. The month following the simulation was later searched in UC Irvine AIMS to determine whether hypertension at emergence was treated by participants or not. We used the Related-Samples Wilcoxon Signed Rank test to compare the median proportion treated before and after simulation. Results Eleven residents participated in the study. One participant was excluded because they went onto outside rotations and data could not be evaluated. During the month prior to the simulation, a total of 53 patients had a MAP greater than 20% baseline and in 26 (43%) of these cases the hypertension was treated pharmacologically by the participant. The median percentage of cases per participant treated pre-simulation was 50% [10.7, 67.6]. In the month following the simulation, a total of 53 cases had a MAP greater than 20% baseline and in 35 (66%) of these cases the hypertension was treated pharmacologically. The calculated median percentage of cases per participant treated post-simulation 65.7% [48.6, 81.2], which is statistically significant (p = 0.037). Conclusion Following the simulation session, participants did show an increase in the percentage of cases of emergence hypertension treated pharmacologically. More participants are needed to draw conclusive Results. AIMS can be a used as a tool when evaluating the impact of simulation on clinical outcomes.

A North American Experience Of Hemoglobin SC Disease, Its Complications, and Management

Background The phenotype of hemoglobin SC (HbSC) disease is distinct from sickle cell anemia (SCA) (HbSS and S/b0) but management of adults is mostly derived from studies of the latter group. Longitudinal observational studies on the complications and outcomes of hemoglobin SC disease are largely confined to centers outside North America. The unique ethnic composition of our cohort, consisting of mostly Western Africans and West Indians, permits further characterization of the HbSC phenotype. Objective to describe the baseline characteristics and long-term complications of a cohort of adult HbSC patients followed in a Canadian sickle cell comprehensive care center. Methods A retrospective observational cohort study was conducted on all adult patients with HbSC disease attending a sickle cell comprehensive care center in Toronto, Canada from 1994 to 2013. Baseline demographics, acute and chronic complications attributable to sickle cell disease, and laboratory data were collected. Medians were used to describe continuous variables, while percentages or ratios for categorical variables. Logistic regression was used to examine factors influencing the main clinical complications. Results 104 patients were included in the analysis, comprising of 38.5% males and 61.5% females. Median length of follow-up was 3.5 years (1 - 19) and median age at last recorded visit was 35 years (18 - 68). Median baseline hemoglobin was 119 g/L (82 - 153 g/L), hematocrit 0.340 (0.250 - 0.440), and fetal hemoglobin (HbF) fraction 1% (0 - 7.7%). Most frequent complications encountered were retinopathy (55.8%) and symptomatic avascular necrosis (27.9%), followed by painful vaso-occlusive crises requiring emergency room visit (23.1%). Presence of retinopathy was associated with higher baseline hemoglobin (OR 2.72 for every 10 g/L of hemoglobin, p = 0.037) and older age (OR 2.72 for every decade, p &lt; 0.001). Acute chest syndrome (7.7%), priapism (7.5% of men), and renal involvement (8.2%), were less common than reported in the literature, while the rates of venous thromboembolism (8.7%), symptomatic infarctive or hemorrhagic stroke (2.9%) were slightly more common. Median right ventricular systolic pressure on 2D-transthoracic echocardiogram was 29 mmHg (17 – 43 mmHg). No patient underwent a right heart catheterization. Two patients died from septic shock, both at the age of 29. Disease-modifying therapy most often consisted of hydroxyurea (28.8%), followed by exchange transfusion (6.7%) and phlebotomies (5.8%). Hydroxyurea significantly increased the median HbF fraction (from 1% to 2.75%, p = 0.004 by related-samples Wilcoxon signed rank test). Conclusion In this large North American cohort of adult patients, we have again shown that HbSC disease is not as benign as traditionally thought. As such, patients with HbSC disease warrant similar follow-up to that provided to SCA. Retinopathy, avascular necrosis and painful vaso-occlusive crises were the most common complications in our study, albeit lower than in other reported cohorts. The frequent use of hydroxyurea in this cohort is quite unique compared to other sickle cell comprehensive care centers reported in the literature. However, therapeutic phlebotomy is less often used compared to the European experience. We also observed a lower frequency of retinopathy, avascular necrosis, painful vaso-occlusive crises, priapism and acute chest syndrome. Whether this observation is due to hydroxyurea use or to other genetic or environmental factors remains to be determined. Further studies are also required to develop a more evidence-based therapeutic strategy for this genotype of Sickle Cell Disease. Disclosures: No relevant conflicts of interest to declare.

Impact of Online Transesophageal Echocardiographic Simulation on Learning to Navigate the 20 Standard Views

To overcome a challenge in transesophageal echocardiographic (TEE) training, an online virtual TEE simulation was developed that allows the user to navigate among the 20 standard views. The TEE probe position and ultrasound plane movements on a 3-dimensional heart model were displayed with the corresponding TEE video recording as the probe was moved among the views. This study evaluated the educational benefit of the virtual TEE application using a pretest/post-test design. Single academic teaching hospital. Ten postgraduate physician volunteers who were novice echocardiographers. In a controlled environment, 10 study subjects completed a 20 multiple-choice question pretest, used the simulation for 1 hour, and then completed a 20 multiple-choice question post-test. Percentages of correct answers for each test were recorded for each subject. The hypothesis that the median improvement in the number of questions correctly answered was different from 0 was tested with a related-samples Wilcoxon signed-rank test. A p value <0.05 was considered significant. A 1-hour exposure to the virtual TEE simulation produced a significant improvement (p = 0.005) in the post-test score (median 80%) compared with the pretest score (median 20%). Using the virtual TEE simulation for 1 hour significantly improves the trainees' knowledge of navigation among the 20 standard TEE views. This application freely is available on the Internet and will be a useful adjunct to TEE training programs.

Pediatric Japanese acupuncture: a one year experience

Acupuncture is a nonpharmacologic option for pain treatment. However, there is little data showing effectiveness in the pediatric population. A pediatric acupuncture outpatient and inpatient consultation service was initiated in November of 2010. One physician evaluated all patients and performed all acupuncture and alternative therapy treatments. Japanese acupuncture, electroacupuncture, moxabustion, laser acupuncture, auricular acupuncture and ion cord current transfer were utilized and available for patient treatment. Data was collected for one year. 71 pediatric patients were treated 351 times with a mean of 4.9 treatments per patient. Age at time of treatment ranged from 4 years to 20 years with a mean of 14.1 years and median of 15 years. Pain was present in 61 of 71 (86%) patients and reported during 263 of 351 (75%) encounters. Treatment performed in the encounters included needle acupuncture (94%), electroacupuncture (79%), laser acupuncture (32%), auricular acupuncture (31%), ion cord current transfer (29%) and moxabustion (12%). Up to three diagnoses were recorded at each patient encounter. The most frequent diagnoses were headache (45%), back pain (27%), obesity (18%), neck pain (16%), abdominal pain (9%), and complex regional pain syndrome (9%). The incidence of intolerance to acupuncture and related therapy was 1%. A numerical self-reported visual analog pain score from 0 to 10 was recorded before and after each treatment. Pain scores averaged 6 prior to treatment and 2.7 following treatment and were compared by the related-samples Wilcoxon signed rank test. The overall decrease in pain score reached clinical and statistical significance with p value < 0.001. Complex regional pain syndrome patients were the most difficult to achieve pain control with mean pain scores changing from 7.9 to 7.1 (p < 0.01 statistically but not clinically significant). Acupuncture is well tolerated and an effective resource for pain relief in pediatrics. Acupuncture is a nonpharmacologic option for pain treatment. However, there is little data showing effectiveness in the pediatric population. A pediatric acupuncture outpatient and inpatient consultation service was initiated in November of 2010. One physician evaluated all patients and performed all acupuncture and alternative therapy treatments. Japanese acupuncture, electroacupuncture, moxabustion, laser acupuncture, auricular acupuncture and ion cord current transfer were utilized and available for patient treatment. Data was collected for one year. 71 pediatric patients were treated 351 times with a mean of 4.9 treatments per patient. Age at time of treatment ranged from 4 years to 20 years with a mean of 14.1 years and median of 15 years. Pain was present in 61 of 71 (86%) patients and reported during 263 of 351 (75%) encounters. Treatment performed in the encounters included needle acupuncture (94%), electroacupuncture (79%), laser acupuncture (32%), auricular acupuncture (31%), ion cord current transfer (29%) and moxabustion (12%). Up to three diagnoses were recorded at each patient encounter. The most frequent diagnoses were headache (45%), back pain (27%), obesity (18%), neck pain (16%), abdominal pain (9%), and complex regional pain syndrome (9%). The incidence of intolerance to acupuncture and related therapy was 1%. A numerical self-reported visual analog pain score from 0 to 10 was recorded before and after each treatment. Pain scores averaged 6 prior to treatment and 2.7 following treatment and were compared by the related-samples Wilcoxon signed rank test. The overall decrease in pain score reached clinical and statistical significance with p value < 0.001. Complex regional pain syndrome patients were the most difficult to achieve pain control with mean pain scores changing from 7.9 to 7.1 (p < 0.01 statistically but not clinically significant). Acupuncture is well tolerated and an effective resource for pain relief in pediatrics.

The Comparison of Performances of Preschool Children on Two Motor Assessments

Understanding children's motor performance on different assessments is important for researchers. The Test of Gross Motor Development-2 (TGMD-2) and the Movement Assessment Battery for Children-2 (MABC-2) are motor assessments that use either a process- or product-oriented scoring approach. However, no studies have examined how performances are related to these two types of assessment. This study compared the performance of preschool children on the TGMD-2 and the MABC-2. 32 children (M age = 4.2 yr., SD = 9) completed each test to assess whether each described motor performance similarly. Significant low to moderate Spearman's rank correlations (r2 range = .13-.40) were found between the subscales of the assessments. A related-samples Wilcoxon signed rank test was not significant between total performances on the TGMD-2 and MABC-2. From a practical standpoint, each assessment provides a similar overall description of motor competence in preschool children. However, each assessment results in scores that present different information about motor performance.