Sandra M. Hurtado Rúa

Distinguishing Benign and Life-Threatening Pneumatosis Intestinalis in Patients With Cancer by CT Imaging Features

OBJECTIVE The purpose of this study is to determine the overall proportion of clinically worrisome and benign pneumatosis intestinalis (PI) occurring in patients with cancer and to evaluate associated risk factors and CT features. MATERIALS AND METHODS We retrospectively studied the CT examinations of 84 patients treated at our tertiary cancer center. Reviewers who were blinded to clinical data and classification analyzed PI in terms of location, pattern (linear, cystic, or both), and associated CT features, including pneumoperitoneum, portomesenteric venous air, bowel wall thickening, bowel dilatation, and ascites. On the basis of the review of clinical information and criteria derived from prior literature, the cases were classified as clinically worrisome PI (underlying bowel disease) or benign PI (diagnosis of exclusion that resolved on follow-up imaging without targeted therapy). Clinical factors reviewed included age, sex, cancer type, steroid use, and chemotherapy administration. RESULTS Forty-seven patients were classified as having benign PI (56%) and the remainder as having clinically worrisome PI (44%). The following imaging features correlated significantly with clinically worrisome PI: bowel wall thickening (p < 0.001), mesenteric stranding (p < 0.001), ascites (p < 0.001), bowel dilatation (p = 0.004), location confined to small bowel (p = 0.012), and portomesenteric venous gas (p = 0.02). Benign PI was significantly associated with PI confined to the colon (p = 0.004). CONCLUSION Benign PI was slightly more prevalent than clinically worrisome PI in our cohort of patients with cancer. The presence of certain CT features (mesenteric stranding, bowel wall thickening, and ascites) and the location of PI may be indicators of more significant bowel disease and, therefore, of clinically worrisome cases. There was no statistical significance achieved for nonimaging clinical factors.

Measuring Longitudinal Myelin Water Fraction in New Multiple Sclerosis Lesions

Objectives Investigating the potential of myelin repair strategies in multiple sclerosis (MS) requires an understanding of myelin dynamics during lesion evolution. The objective of this study is to longitudinally measure myelin water fraction (MWF), an MRI biomarker of myelin, in new MS lesions and to identify factors that influence their subsequent myelin content. Methods Twenty-three MS patients were scanned with whole-brain Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) MWF mapping at baseline and median follow-up of 6 months. Eleven healthy controls (HC) confirmed the reproducibility of FAST-T2 in white matter regions of interests (ROIs) similar to a lesion size. A random-effect-model was implemented to determine the association between baseline clinical and lesion variables and the subsequent MWF. Results ROI-based measurements in HCs were highly correlated between scans [mean r = 0.893 (.764–.967)]. In MS patients, 38 gadolinium enhancing (Gd+) and 25 new non-enhancing (Gd−) T2 hyperintense lesions (5.7 months, ±3.8) were identified. Significant improvement in MWF was seen in Gd+ lesions (0.035 ± 0.029, p < 0.001) as compared to Gd− lesions (0.006 ± 0.017, p = 0.065). In the model, a higher baseline MWF (p < 0.001) and the presence of Gd (p < 0.001) were associated with higher subsequent MWF. Conclusions FAST T2 provides a clinically feasible method to quantify MWF in new MS lesions. The observed influence of baseline MWF, which represents a combined effect of both resolving edema and myelin change within acute lesions, suggests that the extent of initial inflammation impacts final myelin recovery.

MRI Analysis of White Matter Myelin Water Content in Multiple Sclerosis: A Novel Approach Applied to Finding Correlates of Cortical Thinning

A novel lesion-mask free method based on a gamma mixture model was applied to myelin water fraction (MWF) maps to estimate the association between cortical thickness and myelin content, and how it differs between relapsing-remitting (RRMS) and secondary-progressive multiple sclerosis (SPMS) groups (135 and 23 patients, respectively). It was compared to an approach based on lesion masks. The gamma mixture distribution of whole brain, white matter (WM) MWF was characterized with three variables: the mode (most frequent value) m1 of the gamma component shown to relate to lesion, the mode m2 of the component shown to be associated with normal appearing (NA) WM, and the mixing ratio (λ) between the two distributions. The lesion-mask approach relied on the mean MWF within lesion and within NAWM. A multivariate regression analysis was carried out to find the best predictors of cortical thickness for each group and for each approach. The gamma-mixture method was shown to outperform the lesion-mask approach in terms of adjusted R2, both for the RRMS and SPMS groups. The predictors of the final gamma-mixture models were found to be m1 (β = 1.56, p < 0.005), λ (β = −0.30, p < 0.0005) and age (β = −0.0031, p < 0.005) for the RRMS group (adjusted R2 = 0.16), and m2 (β = 4.72, p < 0.0005) for the SPMS group (adjusted R2 = 0.45). Further, a DICE coefficient analysis demonstrated that the lesion mask had more overlap to an ROI associated with m1, than to an ROI associated with m2 (p < 0.00001), and vice versa for the NAWM mask (p < 0.00001). These results suggest that during the relapsing phase, focal WM damage is associated with cortical thinning, yet in SPMS patients, global WM deterioration has a much stronger influence on secondary degeneration. Through these findings, we demonstrate the potential contribution of myelin loss on neuronal degeneration at different disease stages and the usefulness of our statistical reduction technique which is not affected by the typical bias associated with approaches based on lesion masks.

CD4 Deficit and Tuberculosis Risk Persist With Delayed Antiretroviral Therapy: 5-Year Data From CIPRA HT-001

SETTING Port-au-Prince, Haiti. OBJECTIVE To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was <200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P < 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P < 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB.

Diversity Efforts, Admissions, and National Rankings: Can We Align Priorities?

Background: Increasing student body diversity is a priority for national health education and professional organizations and for many medical schools. However, national rankings of medical schools, such as those published by U.S. News & World Report, place a heavy emphasis on grade point average (GPA) and Medical College Admissions Test (MCAT) scores, without considering student body diversity. These rankings affect organizational reputation and admissions outcomes, even though there is considerable controversy surrounding the predictive value of GPA and MCAT scores. Summary: Our aim in this article was to explore the relationship between standard admissions practices, which typically aim to attract students with the highest academic scores, and student body diversity. We examined how changes in GPA and MCAT scores over 5 years correlated with the percentage of enrolled students who are underrepresented in medicine. In a majority of medical schools in the United States from 2005 to 2009, average GPA and MCAT scores of applicants increased, whereas the percentage of enrolled students who are underrepresented in medicine decreased. Conclusions: Our findings suggest that efforts to increase the diversity of medical school student bodies may be complicated by a desire to maintain high average GPA and MCAT scores. We propose that U.S. News revise its ranking methodology by incorporating a new diversity score into its student selectivity score and by reducing the weight placed on GPA and MCAT scores.

A transformation class for spatio-temporal survival data with a cure fraction

We propose a hierarchical Bayesian methodology to model spatially or spatio-temporal clustered survival data with possibility of cure. A flexible continuous transformation class of survival curves indexed by a single parameter is used. This transformation model is a larger class of models containing two special cases of the well-known existing models: the proportional hazard and the proportional odds models. The survival curve is modeled as a function of a baseline cumulative distribution function, cure rates, and spatio-temporal frailties. The cure rates are modeled through a covariate link specification and the spatial frailties are specified using a conditionally autoregressive model with time-varying parameters resulting in a spatio-temporal formulation. The likelihood function is formulated assuming that the single parameter controlling the transformation is unknown and full conditional distributions are derived. A model with a non-parametric baseline cumulative distribution function is implemented and a Markov chain Monte Carlo algorithm is specified to obtain the usual posterior estimates, smoothed by regional level maps of spatio-temporal frailties and cure rates. Finally, we apply our methodology to melanoma cancer survival times for patients diagnosed in the state of New Jersey between 2000 and 2007, and with follow-up time until 2007.

The Effect of Regional Analgesia on Vascular Tone in Hip Arthroplasty Patients

BackgroundWhile it is assumed that neuraxial analgesia and pain management may beneficially influence perioperative hemodynamics, few studies provided data quantifying such effects and none have assessed the potential contribution of the addition of a nerve block.Questions/PurposesThis clinical trial compared the visual analog scale (VAS) scores and measurement of arterial tone using augmentation index of patients who received combined spinal–epidural (CSE) only to patients who received both CSE and lumbar plexus block.MethodsAfter obtaining written consent, 92 patients undergoing total hip arthroplasty were randomized to receive either CSE or CSE with lumbar plexus block (LPB). Perioperative pain and arterial tone were measured using VAS scores and augmentation index (AI) respectively, at baseline and at various times postoperatively.ResultsAfter the exclusion of 2 patients, 44 patients received CSE alone and 46 patients received CSE and LPB. Patient demographics and perioperative characteristics were similar in both groups. AI continuously decreased after placement of a CSE with or without LBP, beyond full resolution of neuraxial and peripheral blockade. Although the LPB group demonstrated a statistically significant reduction of VAS pain scores in the postanesthesia care unit (PACU; P < 0.05), overall, the addition of a LPB did not significantly reduce the AI when compared to the control group.ConclusionThe addition of a LPB provided better pain control in the PACU but did not reduce the AI, compared to the control group. We conclude that the addition of a LPB may have limited ability to affect arterial tone in the presence of a continuous infusion of epidural analgesics. In summary, the addition of a LPB in patients undergoing total hip arthroplasty is clinically effective and provided better pain control, especially in the immediate postoperative period. The continuous decrease on the AI in both groups beyond the full resolution of the neuroaxial and LPB will require further studies.

The Choice of Prior Distribution for A Covariance Matrix in Multivariate Meta-Analysis: A Simulation Study

Bayesian meta-analysis is an increasingly important component of clinical research, with multivariate meta-analysis a promising tool for studies with multiple endpoints. Model assumptions, including the choice of priors, are crucial aspects of multivariate Bayesian meta-analysis (MBMA) models. In a given model, two different prior distributions can lead to different inferences about a particular parameter. A simulation study was performed in which the impact of families of prior distributions for the covariance matrix of a multivariate normal random effects MBMA model was analyzed. Inferences about effect sizes were not particularly sensitive to prior choice, but the related covariance estimates were. A few families of prior distributions with small relative biases, tight mean squared errors, and close to nominal coverage for the effect size estimates were identified. Our results demonstrate the need for sensitivity analysis and suggest some guidelines for choosing prior distributions in this class of problems. The MBMA models proposed here are illustrated in a small meta-analysis example from the periodontal field and a medium meta-analysis from the study of stroke. Copyright

Five-Factor Personality Traits and RIASEC Interest Types: A Multivariate Meta-Analysis

Determining the relationships between five-factor model (FFM) personality dimensions and Realistic, Investigative, Artistic, Social, Enterprising, and Conventional (RIASEC) types is important for counselors and clients during the career choice process. There have been mixed findings regarding this relationship, necessitating this research. The purpose of this study was to determine the relationship between the FFM and RIASEC interest types employing a multivariate meta-regression meta-analysis. Thirty-four studies with 43 independent samples comprising 19,872 participants were employed. Moderator variables included mean age, country of sample, publication year, and FFM and RIASEC Measurement Scales. Estimated correlations between FFM and RIASEC scores ranged from −.08 to .36 suggesting that personality and interests are more distinct constructs than previously thought. FFM Measurement Scales and RIASEC scores by country of sample are important moderating variables in the FFM-RIASEC relationship. The findings have important implications for counseling and research.

Abstract CT309: Influencing the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence

Background: Bone marrow derived endothelial progenitor cells (EPCs) and copper-dependent angiogenic pathways are critical to the metastatic process. Copper depletion (CD) therapy inhibits tumor metastases in preclinical models. We hypothesized that TM-associated CD would reduce EPCs in pts at high risk for BC recurrence, and we explored the relationship between CD and its effects on the tumor microenvironment in pre-clinical models. Methods: In this single arm, phase II study, BC pts at high risk for recurrence, defined as node positive triple negative (TN), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. We CD’d to maintain ceruloplasmin (Cp) between 5-17 mg/dl for 2 years or until relapse. The primary endpoint was change in EPCs measured before and during treatment with TM. Secondary endpoints included tolerability, safety, and efficacy of CD. Laboratory studies: MDA-LM2-luciferase cells were implanted into CB17-SCID mice gavaged with water or TM. The tumors were quantified by bioluminescence images (BLI). We measured Cp oxidase to determine copper status. Western blots were used to assess LOX activity, and IHC was used to quantify collagen cross-linking and CD11b+ macrophage infiltration. Results: We enrolled 43 pts. Treatment duration was 24 cycles (each cycle is 28 days) for the primary study. A total of 752 cycles were completed in 2 years. The mean age was 49 (range 29-66). Mean Cp level decreased from 29 at baseline to 16 (p Citation Format: Nancy Chan, Naomi Kornhauser, Maureen Ward, Amy Willis, Tessa Cigler, Ellen Chuang, Anne Moore, Diana Donovan, Sarah E. Schneider, Christina Lam, David J. Warren, Anna Rubinchik, Sandra Hurtado Rua, Sharrell Lee, Maureen Lane, Vivek Mittal, Linda Vahdat. Influencing the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT309. doi:10.1158/1538-7445.AM2014-CT309