Hayley Wheeler Leatham, MD

All Publications

• Clinical factors associated with cutaneous histopathologic findings in dermatomyositis JOURNAL OF CUTANEOUS PATHOLOGY Wolstencroft, P. W., Rieger, K. E., Leatham, H. W., Fiorentino, D. F. 2019; 46 (6): 401–10

  View details for DOI 10.1111/cup.13442

  View details for Web of Science ID 000466179800002

• Clinical factors associated with cutaneous histopathologic findings in dermatomyositis. Journal of cutaneous pathology Wolstencroft, P. W., Rieger, K. E., Leatham, H. W., Fiorentino, D. F. 2019

  Abstract

  BACKGROUND: Common histopathologic findings in cutaneous dermatomyositis include vacuolar interface with dyskeratosis, mucin, and perivascular inflammation. Data examining the relationships between these and other histologic abnormalities, or their dependence on biopsy site, and medications are limited.METHODS: Using 228 dermatomyositis skin biopsies and statistical analyses including Chi-squared analyses, calculations of relative risk, and adjusted generalized estimating equation regressions, we investigated relationships between 14 histopathologic findings and the impact of clinical factors on these findings.RESULTS: In biopsies taken from sites of visible rash, interface dermatitis was seen in 91%, and 95% had at least one of perivascular inflammation, mucin, or basal vacuolization. Vascular abnormalities were not closely associated with epidermal or inflammatory findings. Concomitant prednisone significantly decreased the odds of basal vacuolization (odds ratio [OR]=0.34, 95% confidence interval [CI]: 0.12-0.98, P-value=0.05), perivascular inflammation (OR=0.19, 95% CI: 0.07-0.53, P-value=0.002), and vessel damage (OR=0.81, 95% CI: 0.68-0.96, P-value=0.02).CONCLUSION: Vasculopathy and classic findings of interface dermatitis may be driven by unique pathways in dermatomyositis. Corticosteroid use may impact skin biopsy findings. There is a need for clinicopathologic correlation when diagnosing dermatomyositis.

  View details for PubMedID 30737826

• Unintended widespread facial autoinoculation of varicella by home microneedling roller device. JAAD case reports Leatham, H., Guan, L., Chang, A. L. 2018; 4 (6): 546–47

  View details for PubMedID 29892671

• Evidence supports blind screening for internal malignancy in dermatomyositis Data from 2 large US dermatology cohorts MEDICINE Leatham, H., Schadt, C., Chisolm, S., Fretwell, D., Chung, L., Callen, J. P., Fiorentino, D. 2018; 97 (2): e9639

  Abstract

  The association between dermatomyositis and internal malignancy is well established, but there is little consensus about the methods of cancer screening that should be utilized.We wished to analyze the prevalence and yield of selected cancer screening modalities in patients with dermatomyositis.We performed a retrospective analysis of 2 large US dermatomyositis cohorts comprising 400 patients.We measured the frequency of selected screening tests used to search for malignancy. Patients with a biopsy-confirmed malignancy were identified. Prespecified clinical and laboratory factors were tested for association with malignancy. For each malignancy we identified the screening test(s) that led to diagnosis and classified these tests as either blind (not guided by suspicious sign/symptom) or triggered (by a suspicious sign or symptom).Forty-eight patients (12.0% of total cohort) with 53 cancers were identified with dermatomyositis-associated malignancy. Twenty-one of these 53 cancers (40%) were diagnosed within 1 year of dermatomyositis symptom onset. In multivariate analysis, older age (P = .0005) was the only significant risk factor for internal malignancy. There was no significant difference in cancer incidence between classic and clinically amyopathic patients. Twenty-seven patients (6.8% of the total cohort) harbored an undiagnosed malignancy at the time of dermatomyositis diagnosis. The majority (59%) of these cancers were asymptomatic and computed tomography (CT) scans were the most common studies to reveal a cancer.This is the largest US cohort studied to examine malignancy prevalence and screening practices in dermatomyositis patients. Our results demonstrate that, while undiagnosed malignancy is present in <10% of US patients at the time of dermatomyositis onset, it is often not associated with a suspicious sign or symptom. Our data suggest that effective malignancy screening of dermatomyositis patients often requires evaluation beyond a history, physical examination, and "age-appropriate" cancer screening-these data may help to inform future guidelines for malignancy screening in this population.

  View details for PubMedID 29480875

• Recurrent Subepidermal Blistering Dermatosis Heralding Disease Relapse in IgA Kappa Multiple Myeloma: Report of a Case and a Review of the Literature. Clinical lymphoma, myeloma & leukemia Leatham, H. W., Novoa, R., Liedtke, M., Kwong, B. Y. 2016; 16 (1): e1-5

  View details for DOI 10.1016/j.clml.2015.11.007

  View details for PubMedID 26708980

• Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Christensen, S., Wheeler, H. M., Straka, M., Tipirneni, A., Kemp, S. M., Zaharchuk, G., Olivot, J., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1024-1028

  Abstract

  The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient.MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed.A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion.Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.002135

  View details for PubMedID 24558095

• Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023

  Abstract

  We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.003857

  View details for PubMedID 24595591

• Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (3): 681-685

  Abstract

  It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume.This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2).Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

  View details for DOI 10.1161/STROKEAHA.111.000135

  View details for Web of Science ID 000315447400024

  View details for PubMedID 23390119

  View details for PubMedCentralID PMC3625664

• Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells MOLECULAR CANCER RESEARCH Liu, Y., Ye, F., Yamada, K., Tso, J. L., Zhang, Y., Nguyen, D. H., Dong, Q., Soto, H., Choe, J., Dembo, A., Wheeler, H., Eskin, A., Schmid, I., Yong, W. H., Mischel, P. S., Cloughesy, T. F., Kornblum, H. I., Nelson, S. F., Liau, L. M., Tso, C. 2011; 9 (12): 1668-1685

  Abstract

  Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated by EDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence.

  View details for DOI 10.1158/1541-7786.MCR-10-0563

  View details for Web of Science ID 000298409600008

  View details for PubMedID 22013079