Publications by authors named "Emile Latour"

23 Publications

  • Page 1 of 1

Validation of a novel patient-operated device for measuring skin barrier function in atopic dermatitis.

Skin Res Technol 2021 Mar 5. Epub 2021 Mar 5.

Department of Dermatology, Oregon Health & Science University, Portland, OR, USA.

Background: Transepidermal water loss (TEWL) and capacitance are used in atopic dermatitis (AD) trials to provide objective data on clinical change and response to therapy. Many barrier devices are costly, limiting their utility. GPSkin is a novel low-cost, patient-operable device that measures both TEWL and capacitance via smartphone application.

Objective: This validation study investigated the correlation of GPSkin with the AquaFlux and Corneometer, and the reliability of these devices, in patients with AD.

Methods: Fifty AD patients with varying disease severity performed self-measurements with GPSkin, while investigators collected data with all 3 devices, on both nonlesional and lesional skin.

Conclusion: GPSkin and AquaFlux demonstrated strong correlation for TEWL on nonlesional and lesional skin by Spearman's correlation (r ), independent of device user. For capacitance, GPSkin and the Corneometer showed moderate correlation when obtained by patients, yet a strong correlation when obtained by a clinician. Despite good correlation, GPSkin showed poor agreement with both the AquaFlux and Corneometer in Bland-Altman plots. GPSkin underestimated both TEWL and capacitance. Overall, the devices had good test-retest reliability. None of the devices could discriminate between AD severity states. While GPSkin marks an exciting advancement in barrier technology, further study is needed for validation on AD skin.
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http://dx.doi.org/10.1111/srt.13027DOI Listing
March 2021

Melanoma toolkit for early detection (MTED) for primary care providers: A pilot study.

Pigment Cell Melanoma Res 2021 Feb 26. Epub 2021 Feb 26.

Oregon Health and Science University, Department of Dermatology.

Introduction: Primary care providers have greater access to patients despite often lacking the appropriate training or time to implement effective skin cancer screenings in their busy practices. Through collaborative efforts with Oregon's War on Melanoma public health campaign and other primary care trainings, we created "Melanoma Toolkit for Early Detection" (MTED): a training curriculum and resource repository for primary care providers.

Methods And Results: MTED consisted of three self-paced modules. Each participant completed a pre- and post-test consisting of demographic, confidence, and image identification questions. A subsequent optional 6-month follow-up image identification test was also provided. Of the 96 participants, 40 completed all the modules, the pre, and post-test. On average, scores increased by 6.0 (95% CI: 3.5 to 8.6) percentage points (P<0.001, paired t-test). The percent of participants reporting confidence with melanoma identification increased significantly from the pre- (23.3%) to the post-test (67.4%), an increase of 44.2 (95% CI: 29.3 to 59.0,) percentage points (P<0.001, McNemar's test).

Discussion: This study shows that an online curriculum such as MTED has the potential to increase PCPs confidence and knowledge. This could subsequently lead to improved early melanoma diagnosis by primary care providers.
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http://dx.doi.org/10.1111/pcmr.12968DOI Listing
February 2021

Mohs Micrographic Surgery for the Treatment of Melanoma: A Cross-Sectional Survey on the Barriers, Prevalence, and Practice.

Dermatol Surg 2021 Feb 8. Epub 2021 Feb 8.

Department of Dermatology, Oregon Health and Science University, Portland, OR Biostatistician, Knight Cancer Institute, Oregon Health and Science University, Portland, OR.

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http://dx.doi.org/10.1097/DSS.0000000000002933DOI Listing
February 2021

Missing data in primary care research: importance, implications and approaches.

Fam Pract 2021 Mar;38(2):200-203

Department of Family Medicine, Oregon Health & Science University, Portland, OR, USA.

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http://dx.doi.org/10.1093/fampra/cmaa134DOI Listing
March 2021

Treatment of pyoderma gangrenosum: A multicenter survey-based study assessing satisfaction and quality of life.

Dermatol Ther 2021 Mar 12;34(2):e14736. Epub 2021 Jan 12.

Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA.

Pyoderma gangrenosum (PG) lacks consensus regarding treatment, and no prior studies assess treatment satisfaction in PG. The objective of this study was to determine patient-reported satisfaction in the treatment of PG, and associations with satisfaction. Methodology was a multicenter cross-sectional survey for patients who received systemic medication(s) to treat PG. Thirty-five patients completed the survey (mean age: 54.0 years, 65.7% female, response rate: 81.4%). Mean (± SD) SATMED-Q score was 75.0 (±16.2, range: 67.6-85.3). Older patients (72.6 ± 23.6 for 18-39 years, 74.4 ± 16.1 for 40-59, 77.1 ± 11.6 for 60+), plus those with higher incomes (72.9 ± 20.3 for $0-49 000; 74.0 ± 17.6 for $50 000-99 000; 79.0 ± 14.6 for $100 000+) and education status (69.4 ± 14.3 for high school equivalent, 72.9 ± 15.9 for undergraduate, 91.7 ± 10.6 for graduate), were more satisfied with treatment. Ulcerative PG had higher SATMED-Q scores (79.0 ± 13.2) than other subtypes (66.2 ± 19.3). For local therapy, wound care, or pain control, 63.2%, 100%, and 75% were satisfied, respectively. The mean DLQI was 8.6 (±7.6, range: 0-29), and higher DLQI was associated with decreased satisfaction. Satisfaction with providers was positively correlated with global satisfaction (Pearson's r = 0.638). The presence of pain and/or depression influenced both SATMED-Q (72.8 ± 18.8 with pain, 78.3 ± 11.2 without; 68.2 ± 18.8 with depression, 80.1 ± 12.2 without) and DLQI scores (12.1 ± 8.1 with pain, 3.9 ± 3.4 without; 10.3 ± 7.1 with depression, 7.4 ± 8.0 without). To optimize the patient experience, non-modifiable associations should be individually considered, and potentially modifiable associations such as satisfaction with specific providers, pain, and depression, may be targeted for management.
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http://dx.doi.org/10.1111/dth.14736DOI Listing
March 2021

Predictors of Virologic Failure Among a Cohort of HIV-infected Children in Southern Ethiopia.

Pediatr Infect Dis J 2021 Jan;40(1):60-65

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Background: Optimal care for children with HIV infection includes timely assessment of treatment failure. Using HIV viral load to define treatment failure remains a challenge in resource-limited settings.

Methods: Children with HIV infection who were already on or starting first-line antiretroviral therapy were enrolled and followed over time. We examined clinical and immunologic predictors of virologic failure (VF), defined as consecutive viral load measurements > 1000 copies/mL (VF). Children were followed every 6 months with clinical assessments, immunologic assays and viral load testing until treatment failure or up to 18 months.

Results: Of the 484 children with complete data, we observed a prevalence of 15% who had VF at enrollment, and 18 who developed VF over 10.5 person-years of follow-up for an incidence of 4.97 [95% CI: 3.04-7.70) per 100 person-years. Lower adherence, lower CD4 T-cell count, lower white blood cells count, lower platelets and a lower glomerular filtration rate were all associated with increased VF. However, in a multivariable analysis, renal function (estimated glomerular filtration rate < 90 mL/min), odds ratio: 11.5 (95% CI: 1.5-63.7), and lower adherence, odds ratio: 3.9 (95% CI: 1.1-13.4), were the only factors associated with development of VF.

Conclusions: We identified a significant risk of VF in children with HIV infection in a prospective cohort study in southern Ethiopia and limited predictive value of clinical variables for VF. This provides further evidence that rapid and reliable viral load testing is needed to adequately address the HIV epidemic, along with implementation of adherence interventions in sub-Saharan Africa.
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http://dx.doi.org/10.1097/INF.0000000000002898DOI Listing
January 2021

Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy.

Front Oncol 2020 7;10:1381. Epub 2020 Aug 7.

Knight Cancer Institute, Oregon Health & Science University, Portland, OR, United States.

Phase 3 studies of immune checkpoint inhibitors have not shown a survival benefit in prostate cancer, but some patients have a profound anticancer response. We evaluated the efficacy of the CTLA-4 targeted agent, ipilimumab, in metastatic prostate cancer patients who had an incomplete biochemical response to initial androgen deprivation therapy (ADT) alone. Ten patients were enrolled, each treated with ipilimumab 10 mg/kg (every 3 weeks for up to 4 doses) with maintenance ipilimumab every 12 weeks for non-progressing patients. The primary endpoint was proportion of patients with an undetectable PSA. The total sample size was 30 patients, but there was an interim analysis planned at 10 for futility. If none of the 10 patients achieved an undetectable PSA, the study would be halted. The study was halted at the interim analysis as none of the 10 patients achieved the primary endpoint, but 30% of patients demonstrated a >50% reduction in PSA, with one patient achieving a >90% reduction in PSA. Peripheral blood mononuclear cells (PBMC) examined by mass cytometry showed that patients with clinical responses had an increase in effector memory T-cell subsets as well as an increase in T-cell expression of T-bet, suggesting induction of a Th1 response. This study provides further evidence that ipilimumab has activity in some patients with prostate cancer and provides further rationale for the development of future studies aimed at identifying a subset of patients with CPRC that are more likely to derive a benefit from treatment with ipilimumab. There is insufficient evidence to use ipilimumab in prostate cancer in routine practice. ClinicalTrials.gov, NCT01498978. Registered 26 December 2011. https://www.clinicaltrials.gov/ct2/show/NCT01498978?term=julie+graff&rank=3.
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http://dx.doi.org/10.3389/fonc.2020.01381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426513PMC
August 2020

A Survey of American College of Mohs Surgery Videography Practices.

Dermatol Surg 2020 Aug 18. Epub 2020 Aug 18.

All authors are affiliated with the Department of Dermatology, Oregon Health and Science University, Portland, Oregon.

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http://dx.doi.org/10.1097/DSS.0000000000002628DOI Listing
August 2020

A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone.

J Immunother Cancer 2020 07;8(2)

Cell, Development & Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA.

Background: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.

Methods: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens.

Results: Five (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression.

Conclusions: Pembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects.

Trial Registration Number: clinicaltrials.gov (NCT02312557).
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http://dx.doi.org/10.1136/jitc-2020-000642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333874PMC
July 2020

Comparison of Three Diagnostic Frameworks for Pyoderma Gangrenosum.

J Invest Dermatol 2021 Jan 20;141(1):59-63. Epub 2020 May 20.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA. Electronic address:

Pyoderma gangrenosum (PG) is an inflammatory condition characterized by chronic cutaneous ulcerations. There are three proposed PG diagnostic frameworks (Su, PARACELSUS, Delphi); however, they lack consensus, and their performance has not yet been validated in a well-defined cohort of patients with PG. In this cross-sectional retrospective cohort study, we sought to evaluate and compare the concordance of these diagnostic frameworks within a single-institution cohort of patients with PG. There were 47 patients from an initial 76 identified by International Classification of Diseases-9 and/or International Classification of Diseases-10 codes, where two PG experts agreed in their diagnosis of PG on the basis of clinical descriptions, photographs, and pathology. This group was the PG cohort by which we evaluated the performance and concordance of the diagnostic frameworks. The PARACELSUS score identified the highest proportion of patients with PG (89% [42 of 47 patients]), followed by Delphi and Su criteria, each at 74% (35 of 47 patients). Assessment of multirater agreement found that the three criteria agreed in their diagnoses for 72% of the patients (95% confidence interval = 60-85%); chance-adjusted agreement was determined to be 0.44 (95% confidence = 0.16-0.68, Fleiss' kappa). Future research should seek to refine these diagnostic frameworks and identify targeted methods of testing to reduce rates of PG misdiagnosis and patient misclassification in clinical trials.
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http://dx.doi.org/10.1016/j.jid.2020.04.019DOI Listing
January 2021

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.

Proc Natl Acad Sci U S A 2020 06 18;117(22):12315-12323. Epub 2020 May 18.

Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239.

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline <50%), and 25 patients were classified as responders (PSA decline ≥50%). Failure to achieve a PSA50 was associated with shorter progression-free survival, time on treatment, and overall survival, demonstrating PSA50's utility. Targeted DNA-sequencing was performed on 26 of 36 biopsies, and RNA-sequencing was performed on 25 of 36 biopsies that contained sufficient material. Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis (GSEA) to identify pathways whose activity state correlated with de novo resistance. gene alterations were more common in nonresponders, although this did not reach statistical significance ( = 0.055). gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.
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http://dx.doi.org/10.1073/pnas.1922207117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275746PMC
June 2020

Characteristics of patients with celiac disease and connective tissue disease overlap.

Int J Dermatol 2020 Aug 25;59(8):e309-e312. Epub 2020 Apr 25.

Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.

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http://dx.doi.org/10.1111/ijd.14892DOI Listing
August 2020

Evaluation of the Effectiveness and Tolerability of Mycophenolate Mofetil and Mycophenolic Acid for the Treatment of Morphea.

JAMA Dermatol 2020 05;156(5):521-528

Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts.

Importance: First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak.

Objective: To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea.

Design, Setting, And Participants: A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate.

Main Outcomes And Measures: The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea.

Results: There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently.

Conclusions And Relevance: This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.
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http://dx.doi.org/10.1001/jamadermatol.2020.0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113833PMC
May 2020

Inpatient teledermatology: Diagnostic and therapeutic concordance among a hospitalist, dermatologist, and teledermatologist using store-and-forward teledermatology.

J Am Acad Dermatol 2020 May 20;82(5):1262-1267. Epub 2020 Jan 20.

Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Background: Inpatient dermatology has been shown to improve patient outcomes at a reduced cost. Few hospitals have dermatologists available. Teledermatology may allow dermatologists to assess hospitalized patients remotely.

Objective: To examine the diagnostic concordance between a hospitalist, dermatologist, and teledermatologist using store-and-forward teledermatology.

Methods: For 100 consecutive patients requiring inpatient dermatology consultation, a survey was conducted by all 3 raters to convey diagnostic impressions and therapeutic recommendations. Complete and partial agreements were assessed using the Cohen kappa statistic.

Results: Inpatient dermatology consultation often resulted in a change in diagnosis (50.9%) and a change in systemic therapy (41.5%). Likewise, virtual teledermatology consultation would have resulted in a change in diagnosis (54.7%) and a change in systemic therapy (47.2%) at similar rates. Comparing the dermatologist and teledermatologists, diagnostic complete and partial agreement were 52.8% and 84.9%, respectively. Systemic therapy agreement was 77.4%. Teledermatologists recommended biopsy more often (68.5% vs 43.5%).

Limitations: Small sample size, tertiary academic medical center, single rater for inpatient teledermatology with specific inpatient niche.

Conclusion: Teledermatologists performed comparably to an in-person dermatologist for the diagnosis and management of hospitalized patients with skin conditions. Teledermatology may be a suitable alternative for delivery of inpatient care if no dermatologist is available.
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http://dx.doi.org/10.1016/j.jaad.2020.01.030DOI Listing
May 2020

Perioperative management of pyoderma gangrenosum.

J Am Acad Dermatol 2020 Aug 9;83(2):369-374. Epub 2020 Jan 9.

Department of Dermatology, Oregon Health & Science University, Center for Health & Healing, Portland, Oregon. Electronic address:

Pyoderma gangrenosum (PG) classically presents with an acute inflammatory stage, characterized by rapid evolution of painful ulcerations. The pathergy associated with PG lesions complicates disease management. Although PG is commonly treated with immunosuppression, some patients have refractory noninflammatory ulcers. In this subpopulation, there are case reports of successful surgical treatment. However, there is no consensus on optimal perioperative treatment for patients with PG undergoing surgery of any kind, PG related or otherwise. Therefore, we conducted a comprehensive literature review describing perioperative management practices and risk factors that may predict response to surgical intervention. We identified 126 cases of surgical intervention in patients with active PG; among these, only 16.7% experienced postoperative disease progression. No perioperative treatments or clinical risk factors were identified as statistically significant predictors of disease recurrence. Although limited by case series design and publication bias, this study is a valuable means of hypothesis generation for this rare condition.
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http://dx.doi.org/10.1016/j.jaad.2020.01.002DOI Listing
August 2020

Invasive Melanoma and Melanoma in Situ Treated With Modified Mohs Micrographic Surgery With En Face Permanent Sectioning: A 10-Year Retrospective Review.

Dermatol Surg 2020 08;46(8):1004-1013

All authors are affiliated with the Department of Dermatology, Oregon Health and Science University School of Medicine, Portland, Oregon.

Background: Successful surgical treatment of cutaneous melanoma is dependent on margin control.

Objective: To determine efficacy of modified Mohs micrographic surgery (mMMS) with en face permanent margins in management of invasive melanoma (IM) and melanoma in situ (MIS).

Methods: A retrospective cohort study evaluating local recurrence, 5-year recurrence-free survival, and 5-year melanoma-specific survival. Overall, 657 melanomas (128 IM and 529 MIS) from 631 patients were treated using mMMS during a 10-year period. Follow-up information was obtained from medical records and telephone encounters.

Results: The median follow-up time was 5.18 years. Most melanomas were located on the head and neck 93.6% (615/657). Margins required for clearance were 0.77 ± 0.44 cm (mean ± SD). Local recurrence was identified in 1.98% (13/657) of melanomas with no local recurrences in IM. Five-year local recurrence-free and melanoma-specific survival rates were estimated to be 96.9% (95% confidence interval [CI]: 94.6%-98.2%) and 99.0% (95% CI: 97.7%-99.6%). There were 5 melanoma-related deaths.

Conclusion: Modified Mohs micrographic surgery is an effective treatment of melanoma as evidenced by low local recurrence rates and high melanoma-specific survival.
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http://dx.doi.org/10.1097/DSS.0000000000002246DOI Listing
August 2020

The utility and challenges of histopathologic evaluation in the diagnosis of nonmalignant skin ulcers.

Wound Repair Regen 2020 03 20;28(2):219-223. Epub 2019 Nov 20.

Oregon Health & Science University, Department of Dermatology, Portland, Oregon, USA.

Histopathologic evaluation of cutaneous ulcers is indicated when the clinical diagnosis is unclear or when ulcers have not responded to standard of care. Many nonmalignant skin ulcers lack specific histologic findings on biopsy and pose a diagnostic challenge. While the usefulness of skin biopsies to diagnose underlying malignancy in ulcerated lesions has been demonstrated in previous studies, their utility in the diagnosis of ulcers of other etiologies has not been reported. We conducted a retrospective study of 45 nonmalignant ulcer biopsies in a 3-year period to compare the histologic diagnosis with the final diagnosis. Additionally, we assessed the diagnostic concordance among three blinded dermatopathologists when reviewing these cases. The leading histologic diagnosis from each of the three observers agreed with the final clinical diagnosis, on average, for 29.6% of the cases (average pairwise kappa = 0.15). Inflammatory ulcers had the lowest concordance between the observers and final diagnosis with an average of 26.0% of cases (average pairwise kappa = 0.06). The observers agreed with each other for 35.6% of the cases (Fleiss' kappa = 0.32). The highest agreement among observers was in the vascular/vasculopathic category (50%, Fleiss' kappa = 0.44). Our results indicate that skin biopsies alone are useful in the evaluation of nonmalignant ulcers to rule out other conditions (e.g. neoplasm) but frequently not sufficient to establish a definitive diagnosis. Additional clinicopathologic correlation is necessary in the final assessment of nonmalignant ulcers to determine the diagnosis. Future research endeavors should explore alternative approaches to more efficiently diagnose nonmalignant skin ulcers.
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http://dx.doi.org/10.1111/wrr.12780DOI Listing
March 2020

Using a Multimedia Tool for Informed Consent in Mohs Surgery: A Randomized Trial Measuring Effects on Patient Anxiety, Knowledge, and Satisfaction.

Dermatol Surg 2020 05;46(5):591-598

Department of Dermatology, Oregon Health and Science University, Portland, Oregon.

Background: Multimedia educational materials have been found to improve aspects of informed consent, although data in the context of Mohs micrographic surgery (MMS) is limited.

Objective: To assess whether a preoperative educational video decreases anxiety, increases comprehension, and improves overall satisfaction for patients undergoing same-day office consultation and MMS.

Materials And Methods: This single-center randomized controlled trial included patients above the age of 18 years undergoing MMS for skin cancer between October 2015 and December 2015. Patients were randomized to view a short preoperative video on MMS in addition to traditional informed consent versus informed consent without video viewing. Questionnaires were used to assess preoperative anxiety, knowledge, and satisfaction.

Results: From 231 consecutively enrolled subjects, there were no significant differences in anxiety (p = .626) or satisfaction (p = .065) between groups. Subjects receiving the intervention were able to more accurately recognize risks of MMS (88% vs 69% of controls, p < .001) and had improved subject-reported confidence in understanding procedural risks and benefits (89% vs 71% of controls, p = .049). Composite comprehension scores were similar between groups (p = .131).

Conclusion: A preoperative MMS educational video increased recognition of procedural risks, but did not improve patient anxiety or satisfaction.
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http://dx.doi.org/10.1097/DSS.0000000000002213DOI Listing
May 2020

Ipilimumab-induced hypophysitis, a single academic center experience.

Pituitary 2019 Oct;22(5):488-496

Division of Endocrinology, Department of Medicine, Oregon Health and Science University, Portland, OR, USA.

Background: Immune checkpoint inhibitors, single or in combination, have recently become a cornerstone for the treatment of many malignancies. Ipilimumab, a CTLA-4 inhibitor, was initially FDA approved for treatment of unresectable or metastatic melanoma and subsequently in combination therapy for other cancers. Ipilimumab-induced hypophysitis (IH) risk of development varies in different studies between 0 and 17%. Furthermore, little is known on how to predict which patients will develop IH and its impact on efficacy of Ipilimumab and survival for these patients. Here we reviewed IH and its impact on progression-free survival (PFS) and overall survival (OS).

Methods: Retrospective, IRB- approved review of consecutive 117 melanoma patients who received ipilimumab between 2011 and 2016 was undertaken. Demographic and clinical characteristics, treatment timing and doses, time to progression after therapy, and survival data were reviewed. Patients were predefined in two groups: patients with and without IH. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study sample. All values are shown as means and standard deviation [mean (SD)] unless indicated otherwise. P < 0.05 was considered to be statistically significant.

Results: Of the 117 patients, 15 (12.8%) with a median age of 62.1 years developed IH. In the IH cohort, 10 (66.7%) were male and were significantly older than females (median 67.7 vs. 50.8; P = 0.009). This difference was not seen in non-IH group. Male patients with IH were significantly older than males without IH (67.7 vs. 56.4 years, P = 0.020), however this difference was not observed in females. No patient who received prior cancer systemic therapy (0/30) developed IH vs. 17.2% (15/72) without prior therapy developed IH (OR 0.00; 95% CI 0.00 to 0.73, P = 0.011). Between IH and non-IH patients, there was no difference in gender, race, ethnicity, BMI, diabetes or autoimmune disease at baseline, number of administered ipilimumab cycles, presence of primary melanoma lesion, or BRAF status. IH and non-IH patients had a similar median PFS (8.1 vs. 6.8 months, HR = 0.51, 95% CI 0.24 to 1.05 P = 0.062) and OS (53.3 vs. 29.5 months; HR 0.66, 95% CI 0.30 to 1.46; P = 0.307).

Conclusion: In this study of melanoma patients treated with Ipilimumab, risk of developing IH was high (almost 13%). Older age in men and no prior cancer therapy were associated with IH higher risk. Development of IH was not associated with PFS or OS. Increased use of immune checkpoint inhibitors in the future will impact IH overall risk, thus awareness is needed. Given the lack of reliable identifiable risk factors, close monitoring of signs and symptoms after each therapy cycle is critical for early detection and treatment of hypophysitis.
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http://dx.doi.org/10.1007/s11102-019-00978-4DOI Listing
October 2019

Phase 1-2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma.

Br J Haematol 2019 09 9;186(6):845-854. Epub 2019 Jun 9.

Penn State Hershey Cancer Institute, Hershey, PA, USA.

Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1-2 study (NCT00764517). Treatment included cladribine 5 mg/m intravenously (IV) (days 1-5), rituximab 375 mg/m IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1-14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose-limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1-14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39% (7/18) in relapsed patients and 97% (38/39) with 80% (31/39) attaining a CR in previously untreated MCL. At a median follow-up of 42 months, median progression-free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95% confidence interval (CI): 2·0-33·0] and 25·0 (95% CI: 12·0-45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.
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http://dx.doi.org/10.1111/bjh.16008DOI Listing
September 2019

Clinical factors influencing the response to intravenous immunoglobulin treatment in cases of treatment-resistant pyoderma gangrenosum.

J Dermatolog Treat 2020 Nov 6;31(7):723-726. Epub 2019 May 6.

Department of Dermatology, Oregon Health & Science University, Center for Health & Healing, Portland, OR, USA.

Pyoderma gangrenosum (PG) is a neutrophilic disorder which classically presents as chronic, painful ulcers on the lower extremities. There is evidence supporting a potential role for intravenous immunoglobulin (IVIG) as adjuvant therapy for treatment-resistant cases; however, it is unclear which patients will most benefit from this modality of treatment - an especially important consideration given the cost per infusion ($5000-$10,000). Thus, we sought to identify the clinical characteristics of patients with refractory PG lesions who demonstrated complete healing when IVIG was incorporated into the therapeutic plan. We performed a literature search of PubMed/MEDLINE and Embase using the keywords 'pyoderma gangrenosum' and 'IVIG'. We also added four institutional cases. Descriptive statistics were used to analyze the data. Significance was set at  < .05. We discovered a total of 45 cases. Twenty-three patients with treatment-resistant PG had complete healing, 22 had partial or unhealed PG ulcers. Patients with one ulcer were 4.1 (95% CI: 1.1-18.5) times more likely to achieve complete healing than patients with more than one ulcer, when IVIG was added ( = .041). There is increased efficacy of IVIG as a treatment for patients with a solitary treatment-resistant PG lesion compared to patients with multiple refractory lesions.
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http://dx.doi.org/10.1080/09546634.2019.1606888DOI Listing
November 2020

Off-label versus on-label prescribing of oral oncology agents on time to receipt of medication in patients with soft tissue sarcoma.

J Oncol Pharm Pract 2019 Sep 13;25(6):1412-1418. Epub 2019 Feb 13.

2 Biostatistics Shared Resource - Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.

Purpose: Off-label prescribing of oral oncology agents has been explored in the treatment of soft tissue sarcoma. The time for a prior authorization approval or rejection for an off-label use can be lengthy. The purpose of this study is to capture this burden by comparing the time it takes for patients to receive off-label versus on-label treatment for their soft tissue sarcoma.

Patients And Methods: In this retrospective chart review study, patients aged 18 and older who received a new prescription for an oral oncology agent for soft tissue sarcoma from one of three sarcoma providers at Oregon Health & Science University oncology clinics between March 2014 and February 2016 were included. Objectives included comparing the effect of off-label to on-label prescribing of oral oncology agents on time to receipt of medication and patient copays for a 30-day supply of oral chemotherapy agent(s).

Results: The time to receipt of medication (median (IQR)) for the off-label group (N = 26) was 12.5 (3.3 to 30.8) days compared to the on-label group (N = 29), which was 8.0 (4.0 to 15.0) days (p = 0.327). The patient cost was $0.00 ($0.00 to $20.00) for the off-label group (N = 18) compared to $3.00 ($0.00 to $68.80) for the on-label group (N = 18) (p = 0.467).

Conclusions: There were no differences in the time to receipt of medication or patient cost between off-label and on-label prescriptions in soft tissue sarcoma patients. Despite lack of statistical significance, these results are meaningful to patient care and require further study to investigate these findings.
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http://dx.doi.org/10.1177/1078155219830471DOI Listing
September 2019

Association Between Postpartum Breast Cancer Diagnosis and Metastasis and the Clinical Features Underlying Risk.

JAMA Netw Open 2019 01 4;2(1):e186997. Epub 2019 Jan 4.

Young Women's Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora.

Importance: In women 45 years or younger, breast cancer diagnosis after childbirth increases the risk for metastasis and death, yet limited data exist to define this window of risk and associated prognostic factors.

Objective: To assess the window of elevated risk for metastasis following a postpartum breast cancer (PPBC) diagnosis and whether clinical prognostic factors are associated with the increased risk.

Design, Setting, And Participants: This multicenter cohort study conducted using cases from the Colorado Young Women's Breast Cancer Cohort diagnosed between January 1, 1981, and December 31, 2014, included 701 women 45 years or younger with stage I to III invasive breast cancer for whom parity data, including time of last childbirth, were available. Data analysis was conducted from July 1 to September 30, 2017. This study involved a tertiary care academic hospital-based breast center and its regional affiliates with cases from the greater Rocky Mountain region.

Exposures: Primary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, and time between breast cancer diagnosis and metastasis.

Main Outcomes And Measures: The primary outcome was distant metastasis-free survival.

Results: A total of 701 women 45 years or younger from the greater Rocky Mountain states region were included in the analysis; mean (SD) age at diagnosis was 37.9 (5.1) years. Breast cancer diagnosis within 10 years after parturition was associated with elevated risk for metastasis, particularly in women with stage I or II disease. In addition, women with PPBC diagnosed within 10 years of a completed pregnancy that was estrogen receptor-positive showed distant metastasis-free survival similar to that of nulliparous patients with estrogen receptor-negative cancer, and women with estrogen receptor-negative PPBC had further reduced metastasis-free survival. Moreover, women with PPBC had increased lymphovascular invasion and lymph node involvement. In addition, tumor-associated Ki67 positivity identified 129 patients with luminal B cancer in the cohort that, independent of parity status, had poorer prognosis compared with patients with luminal A cancer, although it did not reach statistical significance.

Conclusions And Relevance: Diagnosis of PPBC within 10 years post partum appears to be associated with an increased risk for metastasis. This increased risk was highest in stages I and II cancer at diagnosis and present in both patients with estrogen receptor-positive and estrogen receptor-negative cancer, persisting in estrogen receptor-positive cases for up to 15 years after diagnosis. Postpartum breast cancer diagnoses were not associated with increased Ki67 index but were associated with increased lymphovascular invasion and lymph node involvement compared with breast cancer in nulliparous patients.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.6997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484560PMC
January 2019