Person: Hurwitz, Shelley
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Hurwitz
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Shelley
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Hurwitz, Shelley
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Publication Automated segmentation of cerebral deep gray matter from MRI scans: effect of field strength on sensitivity and reliability(BioMed Central, 2017) Chu, Renxin; Hurwitz, Shelley; Tauhid, Shahamat; Bakshi, RohitBackground: The cerebral subcortical deep gray matter nuclei (DGM) are a common, early, and clinically-relevant site of atrophy in multiple sclerosis (MS). Robust and reliable DGM segmentation could prove useful to evaluate putative neuroprotective MS therapies. The objective of the study was to compare the sensitivity and reliability of DGM volumes obtained from 1.5T vs. 3T MRI. Methods: Fourteen patients with MS [age (mean, range) 50.2 (32.0–60.8) years, disease duration 18.4 (8.2–35.5) years, Expanded Disability Status Scale score 3.1 (0–6), median 3.0] and 15 normal controls (NC) underwent brain 3D T1-weighted paired scan-rescans at 1.5T and 3T. DGM (caudate, thalamus, globus pallidus, and putamen) segmentation was obtained by the fully automated FSL-FIRST pipeline. Both raw and normalized volumes were derived. Results: DGM volumes were generally higher at 3T vs. 1.5T in both groups. For raw volumes, 3T showed slightly better sensitivity (thalamus: p = 0.02; caudate: p = 0.10; putamen: p = 0.02; globus pallidus: p = 0.0004; total DGM: p = 0.01) than 1.5T (thalamus: p = 0.05; caudate: p = 0.09; putamen: p = 0.03; globus pallidus: p = 0.0006; total DGM: p = 0.02) for detecting DGM atrophy in MS vs. NC. For normalized volumes, 3T but not 1.5T detected atrophy in the globus pallidus in the MS group. Across all subjects, scan-rescan reliability was generally very high for both platforms, showing slightly higher reliability for some DGM volumes at 3T. Raw volumes showed higher reliability than normalized volumes. Raw DGM volume showed higher reliability than the individual structures. Conclusions: These results suggest somewhat higher sensitivity and reliability of DGM volumes obtained from 3T vs. 1.5T MRI. Further studies should assess the role of this 3T pipeline in tracking potential MS neurotherapeutic effects.Publication Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients(American Diabetes Association, 2013) Garg, Rajesh; Hurwitz, Shelley; Turchin, Alexander; Trivedi, ApoorvaOBJECTIVE Hypoglycemia is associated with increased mortality in hospitalized patients. We investigated the relationship between spontaneous hypoglycemia versus insulin-associated hypoglycemia and mortality in hospitalized patients. RESEARCH DESIGN AND METHODS Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values >70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness. RESULTS There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P < 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P < 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P < 0.0001), with much higher CCI (2.4 vs. 1.1%, P < 0.0001). Mortality was higher in the NTH group compared with the ITH group (P < 0.0001) but lower in the NTC group compared with the ITC group (P < 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P < 0.0001). CONCLUSIONS Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients.Publication 4,871 Emergency Airway Encounters by Air Medical Providers: A Report of the Air Transport Emergency Airway Management (NEAR VI: “A-TEAM”) Project(Department of Emergency Medicine, University of California, Irvine School of Medicine, 2014) Brown, Calvin; Cox, Kelly; Hurwitz, Shelley; Walls, RonIntroduction: Pre-hospital airway management is a key component of resuscitation although the benefit of pre-hospital intubation has been widely debated. We report a large series of pre-hospital emergency airway encounters performed by air-transport providers in a large, multi-state system. Methods: We retrospectively reviewed electronic intubation flight records from an 89 rotorcraft air medical system from January 01, 2007, through December 31, 2009. We report patient characteristics, intubation methods, success rates, and rescue techniques with descriptive statistics. We report proportions with 95% confidence intervals and binary comparisons using chi square test with p-values <0.05 considered significant. Results: 4,871 patients had active airway management, including 2,186 (44.9%) medical and 2,685 (55.1%) trauma cases. There were 4,390 (90.1%) adult and 256 (5.3%) pediatric (age ≤ 14) intubations; 225 (4.6%) did not have an age recorded. 4,703 (96.6%) had at least one intubation attempt. Intubation was successful on first attempt in 3,710 (78.9%) and was ultimately successful in 4,313 (91.7%). Intubation success was higher for medical than trauma patients (93.4% versus 90.3%, p=0.0001 JT test). 168 encounters were managed primarily with an extraglottic device (EGD). Cricothyrotomy was performed 35 times (0.7%) and was successful in 33. Patients were successfully oxygenated and ventilated with an endotracheal tube, EGD, or surgical airway in 4809 (98.7%) encounters. There were no reported deaths from a failed airway. Conclusion: Airway management, predominantly using rapid sequence intubation protocols, is successful within this high-volume, multi-state air-transport system.Publication Morphological Characteristics of Brain Tumors Causing Seizures(American Medical Association (AMA), 2010) Lee, Jong; Wen, Patrick; Hurwitz, Shelley; Black, Peter; Kesari, Santosh; Drappatz, Jan; Golby, Alexandra; Wells, William; Warfield, Simon; Kikinis, Ron; Bromfield, Edward B.Objective: To quantify size and localization differences between tumors presenting with seizures vs nonseizure neurological symptoms. Design: Retrospective imaging survey. We performed magnetic resonance imaging–based morphometric analysis and nonparametric mapping in patients with brain tumors. Setting: University-affiliated teaching hospital. Patients or Other Participants: One hundred twenty-four patients with newly diagnosed supratentorial glial tumors. Main Outcome Measures: Volumetric and mapping methods were used to evaluate differences in size and location of the tumors in patients who presented with seizures as compared with patients who presented with other symptoms. Results: In high-grade gliomas, tumors presenting with seizures were smaller than tumors presenting with other neurological symptoms, whereas in low-grade gliomas, tumors presenting with seizures were larger. Tumor location maps revealed that in high-grade gliomas, deep-seated tumors in the pericallosal regions were more likely to present with nonseizure neurological symptoms. In low-grade gliomas, tumors of the temporal lobe as well as the insular region were more likely to present with seizures. Conclusions: The influence of size and location of the tumors on their propensity to cause seizures varies with the grade of the tumor. In high-grade gliomas, rapidly growing tumors, particularly those situated in deeper structures, present with non–seizure-related symptoms. In low-grade gliomas, lesions in the temporal lobe or the insula grow large without other symptoms and eventually cause seizures. Quantitative image analysis allows for the mapping of regions in each group that are more or less susceptible to seizures. Seizures are encountered in a majority of patients with primary brain tumors and are a major cause of morbidity in these patients.1,2 Thirty percent to 50% of patients experience a seizure by the time their tumors are diagnosed, and an additional 6% to 45% of patients who do not initially present with seizures eventually develop them.3- 5 Characteristics of brain tumors and their mechanism in causing seizures in patients are incompletely understood.4,6 Low-grade, well-differentiated gliomas,1,6- 9 cortically located tumors,3,10- 14 and location in the temporal/frontal and motor/sensory cortices6,8,15- 17 are more frequently associated with seizures. Although there is a high incidence of seizures in these patients, treatment strategies remain poorly defined. Prophylactic anticonvulsant therapy, shown to be ineffective in preventing seizures in patients with brain tumors in multiple large-scale studies,12,18- 20 is not recommended by the American Academy of Neurology.5 Nonetheless, prophylaxis remains a widespread practice21 because of difficulty in determining which patients are at greatest risk for seizures. Determination of morphometric factors influencing seizures would help in identifying patients at greatest risk for early, targeted treatment and prevent potentially toxic, unnecessary treatment in patients at minimal risk. Although studies examining brain tumors in relationship to epilepsy have localized tumors to a particular lobe,10 few studies have performed quantitative volumetric or spatial mapping analysis of tumors in relation to their epileptogenic potential. Regions within a particular lobe are likely to exhibit different epileptogenic potential to tumor invasion and tumors frequently affect multiple contiguous lobes.6 Modern imaging techniques allow for analysis of lesions over a large group of subjects through registration and mapping techniques. In this study, we used these techniques to examine the size and location of primary supratentorial glial brain tumors and characterized their propensity to cause seizures at presentation.Publication The Effect of Dimethyl Fumarate on Cerebral Gray Matter Atrophy in Multiple Sclerosis(Springer Healthcare, 2016) Dupuy, Sheena L.; Tauhid, Shahamat; Hurwitz, Shelley; Chu, Renxin; Yousuf, Fawad; Bakshi, RohitIntroduction: The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing–remitting (RR) MS. Methods: We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1.1 ± 1.2, timed 25-foot walk (T25FW) 4.6 ± 0.8 s] and eight patients on noDMT (age 42.5 ± 6.6 years, EDSS 1.7 ± 1.1, T25FW 4.4 ± 0.6 s). Baseline and 1-year 3D T1-weighted 3T MRI was processed with automated pipelines (SIENA, FSL-FIRST) to assess percentage whole brain volume change (PBVC) and deep GM (DGM) atrophy. Group differences were assessed by analysis of covariance, with time between MRI scans as a covariate. Results: Over 1 year, the DMF group showed a lower rate of whole brain atrophy than the noDMT group (PBVC: −0.37 ± 0.49% vs. −1.04 ± 0.67%, p = 0.005). The DMF group also had less change in putamen volume (−0.06 ± 0.22 vs. −0.32 ± 0.28 ml, p = 0.02). There were no significant on-study differences between groups in caudate, globus pallidus, thalamus, total DGM volume, T2 lesion volume, EDSS, or T25FW (all p > 0.20). Conclusions: These results suggest a treatment effect of DMF on GM atrophy appearing at 1 year after starting therapy. However, due to the retrospective study design and sample size, these findings should be considered preliminary, and require confirmation in future investigations. Funding Biogen.Publication MRI detection of hypointense brain lesions in patients with multiple sclerosis: T1 spin-echo vs. gradient-echo(Elsevier BV, 2015) Dupuy, Sheena; Tauhid, Shahamat; Kim, Gloria; Chu, Renxin; Tummala, Subhash; Hurwitz, Shelley; Bakshi, RohitObjective Compare T1 spin-echo (T1SE) and T1 gradient-echo (T1GE) sequences in detecting hypointense brain lesions in multiple sclerosis (MS). Background Chronic hypointense lesions on T1SE MRI scans are a surrogate of severe demyelination and axonal loss in MS. The role of T1GE images in the detection of such lesions has not been clarified. Design/methods In 45 patients with MS [Expanded Disability Status Scale (EDSS) score (mean ± SD) 3.5 ± 2.0; 37 relapsing-remitting (RR); 8 secondary progressive (SP)], cerebral T1SE, T1GE, and T2-weighted fluid-attenuated inversion-recovery (FLAIR) images were acquired on a 1.5 T MRI scanner. Images were re-sampled to axial 5 mm slices before directly comparing lesion detectability using Jim (v.7, Xinapse Systems). Statistical methods included Wilcoxon signed rank tests to compare sequences and Spearman correlations to test associations. Results Considering the entire cohort, T1GE detected a higher lesion volume (5.90 ± 6.21 vs. 4.17 ± 4.84 ml, p < 0.0001) and higher lesion number (27.82 ± 20.66 vs. 25.20 ± 20.43, p < 0.05) than T1SE. Lesion volume differences persisted when considering RR and SP patients separately (both p < 0.01). A higher lesion number by T1GE was seen only in the RR group (p < 0.05). When comparing correlations between lesion volume and overall neurologic disability (EDSS score), T1SE correlated with EDSS (Spearman r = 0.29, p < 0.05) while T1GE (r = 0.23, p = 0.13) and FLAIR (r = 0.24, p = 0.12) did not. Conclusion Our data suggest that hypointense lesions on T1SE and T1GE are not interchangeable in patients with MS. Based on these results, we hypothesize that T1GE shows more sensitivity to lesions at the expense of less pathologic specificity for tissue destruction than T1SE.Publication The Effect of Glatiramer Acetate on Spinal Cord Volume in Relapsing‐Remitting Multiple Sclerosis(John Wiley and Sons Inc., 2016) Singhal, Tarun; Tauhid, Shahamat; Hurwitz, Shelley; Neema, Mohit; Bakshi, RohitABSTRACT BACKGROUND Spinal cord atrophy occurs early in the multiple sclerosis (MS) disease course, is closely related to physical disability, and is a putative neuroprotective therapeutic outcome measure. OBJECTIVE This pilot study explored glatiramer acetate (GA)’s effect on spinal cord volume in patients with relapsing‐remitting MS (RRMS). METHODS Fifteen patients receiving daily subcutaneous GA were prospectively followed. At baseline, age was 43.6 ± 7.4 years, Expanded Disability Status Scale (EDSS) score was 1.4 ± 1.5, timed 25‐foot walk (T25FW) was 4.7 ± 1.1 seconds, and time on GA was 2.1 ± 3.1 years. Healthy controls (n = 10) with similar age and sex to the patients were also enrolled. The spinal cord was imaged at baseline and one year later with 3T magnetic resonance imaging. An active surface method measured the C1–C7 spinal cord volume from which we calculated the normalized area. RESULTS The spinal cord area showed no significant change in the MS group over one year (P = .19). Furthermore, the change in the spinal cord area did not differ significantly between the MS and control groups over one year (P = .26). In the MS group, the EDSS score (P = .44) and T25FW (P = .92) did not change significantly on‐study. CONCLUSION In this pilot study of RRMS, GA therapy was not associated with any ongoing spinal cord atrophy or any difference in the one‐year rate of spinal cord area change versus healthy controls. These results paralleled the lack of clinical worsening and may reflect a treatment effect of GA. Further studies are needed to confirm these preliminary findings.Publication Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients(BMJ Publishing Group, 2017) Garg, Rajesh; Schuman, Brooke; Hurwitz, Shelley; Metzger, Cheyenne; Bhandari, ShreyaObjective: To evaluate whether saxagliptin is non-inferior to basal-bolus insulin therapy for glycemic control in patients with controlled type 2 diabetes mellitus (T2DM) admitted to hospital with non-critical illnesses. Research design and methods This was an open-label, randomized controlled clinical trial. Patients received either saxagliptin or basal-bolus insulin, both with correctional insulin doses. The main study outcome was the mean daily blood glucose (BG) after the first day of randomization. Results: Of 66 patients completing the study, 33 (age 69±10 years, 40% men) were randomized to saxagliptin and 33 (age 67±10 years, 52% men) to basal-bolus insulin therapy. The mean daily BG was 149.8±22.0 mg/dL in the saxagliptin group and 146.9±30.5 mg/dL in the insulin group (p=0.59). With an observed group difference of 2.9 mg/dL and an a priori margin of 20 mg/dL, inferiority of saxagliptin was rejected in favor of non-inferiority (p=0.007). There was no significant difference in the percentage of high or low BG values. The insulin group received a higher number of insulin injections (2.3±1.7/day vs 1.2±1.9/day; p<0.001) as well as a higher daily insulin dose (13.3±12.9 units/day vs 2.4±3.3 units/day; p<0.001) than did the saxagliptin group. Continuous BG monitoring showed that glycemic variability was lower in the saxagliptin group as compared to the insulin group. Patient satisfaction scores were similar in the two groups. Conclusions: We conclude that saxagliptin use is non-inferior to basal-bolus insulin in non-critically ill hospitalized patients with T2DM controlled on 0–2 oral agents without insulin. Saxagliptin use may decrease glycemic variability in these patients. Trial registration number NCT02182895.Publication Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study(Elsevier, 2016) Almirol, Ellen A.; Chi, Lisa Y.; Khurana, Bharti; Hurwitz, Shelley; Bluman, Eric M.; Chiodo, Christopher; Matzkin, Elizabeth; Baima, Jennifer; Leboff, MerylAims In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Methods: Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. Results: After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). Conclusions: In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine the effects of TPTD treatment on stress fracture healing in premenopausal women.