Research Spotlight

Kivelevitch, D., J. Frieder, I. Watson, S. Y. Paek and M. A. Menter (2018). “Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.” Expert Opin Pharmacother 19(6): 561-575.

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INTRODUCTION: Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients’ quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. Expert opinion: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Kivelevitch, D., J. Frieder, I. Watson, S. Y. Paek and M. A. Menter (2018). “Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.” Expert Opin Pharmacother 19(6): 561-575.

Full text of this article.

INTRODUCTION: Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients’ quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. Expert opinion: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Kim, T. W., E. Choi, J. Park, D. H. Shin, S. K. Jung, S. Seok, K. H. Cho, J. Y. Kim, D. Y. Kim, T. H. Kim, Y. K. Suh, Y. J. Kim and S. H. Moon (2018). “Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single Institute in Korea.” Cancer Res Treat 50(2): 335-344.

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PURPOSE: This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty-four treatment-naive patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software. RESULTS: The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565+/-0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively. CONCLUSION: The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

Keuffel, E., P. A. McCullough, T. M. Todoran, E. S. Brilakis, S. R. Palli, M. P. Ryan and C. Gunnarsson (2018). “The effect of major adverse renal cardiovascular event (MARCE) incidence, procedure volume, and unit cost on the hospital savings resulting from contrast media use in inpatient angioplasty.” J Med Econ 21(4): 356-364.

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OBJECTIVE: To determine the net economic impact of switching from low-osmolar contrast media (LOCM) to iso-osmolar contrast media (IOCM; iodixanol) in patients undergoing inpatient coronary or peripheral angioplasty in the United States (US). METHODS: A budget impact model (BIM) was developed from a hospital perspective. Nationally representative procedural and contrast media prevalence rates, along with MARCE (major adverse renal cardiovascular event) incidence and episode-related cost data were derived from Premier Hospital Data (October 2014 to September 2015). A previously estimated relative risk reduction in MARCE associated with IOCM usage (9.3%) was applied. The higher cost of IOCM was included when calculating the net impact estimates at the aggregate, hospital type, and per hospital levels. One-way (+/-25%) and probabilistic sensitivity analyses identified the model’s most important inputs. RESULTS: Based on weighted analysis, 513,882 US inpatient angioplasties and 35,610 MARCE cases were estimated annually. Switching to an “IOCM only” strategy from a “LOCM only” strategy increases contrast media cost, but prevents 2,900 MARCE events. The annual budget impact was an estimated saving of $30.71 million, aggregated across all US hospitals, $6,316 per hospital, or $60 per procedure. Net savings were maintained across all univariate sensitivity analyses. While MARCE/event-free cost differential was the most important factor driving total net savings for hospitals in the Northeast and West, procedural volume was important in the Midwest and rural locations. CONCLUSIONS: Switching to an “IOCM only” strategy from a “LOCM only” approach yields substantial net global savings to hospitals, both at the national level and within hospital sub-groups. Hospital administrators should maintain awareness of the factors that are likely to be more influential for their hospital and recognize that purchasing on the basis of lower contrast media cost may result in higher overall costs for patients undergoing inpatient angioplasty.

Kennedy, L., L. Hargrove, J. Demieville, A. Karstens, H. Jones, S. DeMorrow, F. Meng, P. Invernizzi, F. Bernuzzi, G. Alpini, S. Smith, A. Akers, V. Meadows and H. Francis (2018). “Blocking H1/H2 histamine receptors inhibits damage/fibrosis in Mdr2(-/-) mice and human cholangiocarcinoma tumorigenesis.” Hepatology. Mar 30. [Epub ahead of print].

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BACKGROUND: Primary Sclerosing Cholangitis (PSC) patients are at risk of developing cholangiocarcinoma (CCA). We have shown that: (i) histamine (HA) increases biliary hyperplasia via H1/H2 histamine receptors (HRs) and (ii) HA levels increase and mast cells (MCs) infiltrate during PSC and CCA. We aimed to examine the effects of chronic treatment with H1/H2HR antagonists on PSC and CCA. METHODS: Wild-type and Mdr2(-/-) mice were treated by osmotic minipumps with saline, mepyramine or ranitidine (10mg/kg BW/day) or a combination of mepyramine/ranitidine for 4 wks. Liver damage was assessed by H&E. We evaluated (i) H1/H2 HR expression; (ii) MC presence; (iii) l-histidine decarboxylase (HDC)/HA axis; (iv) cholangiocyte proliferation/bile duct mass (v) fibrosis/hepatic stellate cell (HSC) activation. Nu/nu mice were implanted with Mz-ChA-1 cells into the hind flanks and treated with saline, mepyramine or ranitidine. Tumor growth was measured and we evaluated: (i) H1/H2HR expression; (ii) proliferation; (iii) MC activation; (iv) angiogenesis and (v) epithelial-mesenchymal transition (EMT). In vitro, human hepatic stellate cells were evaluated for H1HR and H2HR expression. Cultured cholangiocytes and CCA lines were treated with saline, mepyramine or ranitidine (25 muM) before evaluating proliferation, angiogenesis, EMT, and potential signaling mechanisms. RESULTS: H1/H2HR and MC presence increased in human PSC and CCA. In H1/H2HR antagonist (alone or in combination)-treated Mdr2(-/-) mice, liver and biliary damage and fibrosis decreased compared to saline treatment. H1/H2HR antagonists decreased tumor growth, serum HA, angiogenesis and EMT. In vitro, H1/H2HR blockers reduced biliary proliferation, and CCA cells had decreased proliferation, angiogenesis, EMT and migration. CONCLUSION: Inhibition of H1/H2HR reverses PSC-associated damage and decreases CCA growth, angiogenesis and EMT. Since PSC patients are at risk of developing CCA, using HR blockers may be therapeutic for these diseases. This article is protected by copyright. All rights reserved.