Fixed-Combination Halobetasol Propionate/Tazarotene Lotion for Psoriasis in Patients With 3%-5% Affected Body Surface Area.

INTRODUCTION: Patients with psoriasis and low body surface area (BSA) involvement often experience substantially reduced quality of life and may be candidates for topical therapies. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) vs vehicle lotion was evaluated in participants with 3% to 5% BSA involvement. METHODS: In two phase 3, multicenter, double-blind, vehicle-controlled, 8-week studies (ClinicalTrial.gov identifiers: NCT02462070/NCT02462122), adults with moderate/severe investigator’s global assessment (IGA) score were randomized 2:1 to once-daily HP/TAZ or vehicle. Pooled post hoc analyses included participants with baseline BSA involvement of 3% to 5%. Measures included treatment success (≥2-grade IGA reduction, clear/almost clear score), reduction in affected BSA, and clinically meaningful improvement (reduction) of ≥4 points on dermatology life quality index (DLQI). RESULTS: Of 418 participants, 232 had baseline BSA involvement of 3% to 5% (HP/TAZ, n=149; vehicle, n=83). At week 8, 42.7% of HP/TAZ-treated participants achieved treatment success, compared with 11.4% of vehicle-treated participants (P< .001). Participants experienced significantly greater reductions in affected BSA at week 8 with HP/TAZ (-36.0%) vs vehicle (-1.6%; P< .001). Larger proportions experienced clinically meaningful DLQI improvements at week 8 with HP/TAZ (64.2%) vs vehicle (47.4%; P< .05). More participants achieved a ≥2-grade improvement in plaque elevation and scaling with HP/TAZ vs vehicle (each comparison, P< .001). Serious adverse events and discontinuations due to treatment-emergent adverse events were rare. CONCLUSIONS: In participants with plaque psoriasis and BSA involvement of 3% to 5%, HP/TAZ provided significantly improved effectiveness after 8 treatment weeks vs vehicle lotion, with clinically meaningful improvements in quality of life. J Drugs Dermatol. 2021;20(8):829-836. doi:10.36849/JDD.6217.

Case report of squamous cell cancer arising in perineal epidermal inclusion cyst, presenting as rapidly enlarging and cavitating lesion.

INTRODUCTION: Cutaneous squamous cell cancer (cSCC) is a common condition, with straight forward and well-known heuristics regarding diagnosis, treatment, and surveillance. cSCC arising in an epidermal inclusion cyst is rare, but not unheard of. In contrast, the authors' are unaware of any prior reports of cSCC arising in an epidermal inclusion cyst within an atypical cavernous and cavitating lesion in the perineum. PRESENTATION OF CASE: A 48-year-old male presented with a cavitating and rapidly growing cutaneous perineal lesion. Preliminary diagnostic procedures (biopsy) showed benign pathology and imaging showed no involvement of perineal organs such as prostate or rectum. Discordance between initial diagnostics and clinical features prompted multi-specialty consultation, including dermatological pathology. Repeat biopsy yielded in situ, possibly invasive squamous cell cancer, arising in the background of an epidermal inclusion cyst. Wide excision with advancement flap reconstruction was employed, with temporary diverting colostomy to avoid perineal sepsis. DISCUSSION: Location and appearance of this lesion provided a diagnostic and treatment challenge requiring multi-specialty involvement for diagnosis and successful treatment. Specialists from urology, general surgery, dermatology, general and dermatological pathology, plastic and reconstructive surgery, colorectal surgery and medical and radiation oncology were involved in diagnosis, treatment plan and execution. None of the specialists involved had seen this singular presentation before, and this created an ownership and management challenge. CONCLUSION: The cavitating, atypical appearance of lesion complicated diagnosis. Location required pre-treatment coordination and deliberation between dermatology, urology, general surgery, and plastic surgery. Malignant degeneration of inclusion cysts, although rare, has to be kept in mind, especially when presenting with rapid growth, and persistence in ruling out malignant diagnosis is fundamental.

Bioremediation in Fractured Rock: 2. Mobilization of Chloroethene Compounds from the Rock Matrix.

A mass balance is formulated to evaluate the mobilization of chlorinated ethene compounds (CE) from the rock matrix of a fractured mudstone aquifer under pre- and postbioremediation conditions. The analysis relies on a sparse number of monitoring locations and is constrained by a detailed description of the groundwater flow regime. Groundwater flow modeling developed under the site characterization identified groundwater fluxes to formulate the CE mass balance in the rock volume exposed to the injected remediation amendments. Differences in the CE fluxes into and out of the rock volume identify the total CE mobilized from diffusion, desorption, and nonaqueous phase liquid dissolution under pre- and postinjection conditions. The initial CE mass in the rock matrix prior to remediation is estimated using analyses of CE in rock core. The CE mass mobilized per year under preinjection conditions is small relative to the total CE mass in the rock, indicating that current pump-and-treat and natural attenuation conditions are likely to require hundreds of years to achieve groundwater concentrations that meet regulatory guidelines. The postinjection CE mobilization rate increased by approximately an order of magnitude over the 5 years of monitoring after the amendment injection. This rate is likely to decrease and additional remediation applications over several decades would still be needed to reduce CE mass in the rock matrix to levels where groundwater concentrations in fractures achieve regulatory standards.

Bioremediation in Fractured Rock: 1. Modeling to Inform Design, Monitoring, and Expectations.

Field characterization of a trichloroethene (TCE) source area in fractured mudstones produced a detailed understanding of the geology, contaminant distribution in fractures and the rock matrix, and hydraulic and transport properties. Groundwater flow and chemical transport modeling that synthesized the field characterization information proved critical for designing bioremediation of the source area. The planned bioremediation involved injecting emulsified vegetable oil and bacteria to enhance the naturally occurring biodegradation of TCE. The flow and transport modeling showed that injection will spread amendments widely over a zone of lower-permeability fractures, with long residence times expected because of small velocities after injection and sorption of emulsified vegetable oil onto solids. Amendments transported out of this zone will be diluted by groundwater flux from other areas, limiting bioremediation effectiveness downgradient. At nearby pumping wells, further dilution is expected to make bioremediation effects undetectable in the pumped water. The results emphasize that in fracture-dominated flow regimes, the extent of injected amendments cannot be conceptualized using simple homogeneous models of groundwater flow commonly adopted to design injections in unconsolidated porous media (e.g., radial diverging or dipole flow regimes). Instead, it is important to synthesize site characterization information using a groundwater flow model that includes discrete features representing high- and low-permeability fractures. This type of model accounts for the highly heterogeneous hydraulic conductivity and groundwater fluxes in fractured-rock aquifers, and facilitates designing injection strategies that target specific volumes of the aquifer and maximize the distribution of amendments over these volumes.

Iron and Electron Shuttle Mediated (Bio)degradation of 2,4-Dinitroanisole (DNAN).

The Department of Defense has developed explosives with the insensitive munition 2,4-dinitroanisole (DNAN), to prevent accidental detonations during training and operations. Understanding the fate and transport of DNAN is necessary to assess the risk it may represent to groundwater once the new ordnance is routinely produced and used. Experiments with ferrous iron or anthrahydroquinone-2,6-disulfonate (AH2QDS) were conducted from pH 6.0 to 9.0 with initial DNAN concentrations of 100 µM. DNAN was degraded by 1.2 mM Fe(II) at pH 7, 8, and 9, and rates increased with increasing pH. Greater than 90% of the initial 100 µM DNAN was reduced within 10 min at pH 9, and all DNAN was reduced within 1 h. AH2QDS reduced DNAN at all pH values tested. Cells of Geobacter metallireducens were added in the presence and absence of Fe(III) and/or anthraquinone-2,6-disulfonate (AQDS), and DNAN was also reduced in all cell suspensions. Cells reduced the compound directly, but both AQDS and Fe(III) increased the reaction rate, via the production of AH2QDS and/or Fe(II). DNAN was degraded via two intermediates: 2-methoxy-5-nitroaniline and 4-methoxy-3-nitroaniline, to the amine product 2,4-diaminoanisole. These data suggest that an effective strategy can be developed for DNAN attenuation based on combined biological-abiotic reactions mediated by Fe(III)-reducing microorganisms.

Electron shuttle-mediated biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine adsorbed to granular activated carbon.

Granular activated carbon (GAC) effectively removes hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) from groundwater but generates RDX-laden GAC that must be disposed of or regenerated. Batch reactors containing GAC to which RDX was preadsorbed were used in experiments to test the potential for adsorbed RDX reduction and daughter product formation using (i) chemically reduced anthrahydroquinone-2,6-disulfonate (AH2QDS), (ii) resting Geobacter metallireducens strain GS-15, and (iii) a combined system containing AQDS and GS-15. Approximately 97.0% of the adsorbed RDX was transformed in each of these experimental systems by 90 h. Chemically reduced AQDS (AH2QDS) transformed 99.2% of adsorbed RDX; formaldehyde was produced rapidly and was stoichiometric (3 mol HCHO per mol RDX). Geobacter metallireducens also reduced RDX with and without AQDS present. This is the first study to demonstrate biological transformation of RDX adsorbed to GAC. Formaldehyde increased and then decreased in biological systems, suggesting a previously unreported capacity for G. metallireducens to oxidize formaldehyde, which was confirmed with resting cell suspensions. These data suggest the masses of GAC waste currently produced by activated carbon at RDX remediation sites can be minimized, decreasing the carbon footprint of the treatment technology. Alternatively, this strategy may be used to develop a Bio-GAC system for ex situ RDX treatment.