Improved patient- and caregiver-reported outcomes distinguish tacrolimus 0.03% from crisaborole in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease that affects 20% of children worldwide and is associated with low patient-reported quality of life (QoL). Crisaborole (CRIS) and tacrolimus 0.03% (TAC) are Food and Drug Administration (FDA)-approved topical treatments for mild to moderate AD with similar clinical efficacy. Utilization of patient-reported outcomes (PROs) may provide meaningful data on the impact of AD treatments on patients and caregivers. This study used PROs to monitor the impact of crisaborole (CRIS) and tacrolimus 0.03% (TAC) on children with mild/moderate atopic dermatitis (AD) and caregiver burden. METHODS: This open-label study randomized 47 child-caregiver dyads to CRIS or TAC for 12 weeks. Disease severity, child quality of life (QoL), itch, pain interference, anxiety, depression, sleep, caregiver burden and caregiver QoL were assessed at baseline, 6 and 12 weeks. RESULTS: A total of 36 dyads completed the study. Children (mean age = 8.0 ± 3.9 years) had mild baseline AD and were diverse by race (39% white; 36% Black) and gender (53% males). Caregivers were mostly female (78%; mean age = 37 ± 7.6 years). Both arms improved disease severity (Eczema Area and Severity Index) from baseline to 12 weeks (CRIS = -2.4 vs. TAC = -1.9). Within-arm analyses comparing baseline to 12 weeks revealed TAC, but not CRIS, improved all child and caregiver PROs except sleep (all p < 0.05). CONCLUSIONS: Our results demonstrated that topical treatment for 12 weeks was more beneficial than 6 weeks, with TAC improving more PROs than CRIS. Future trials should implement PROs to fully understand the impact of AD treatments.

Opioid Prescribing Patterns After Micrographic Surgery: A Follow-up Retrospective Chart Review.

BACKGROUND: The abuse of opioids has reached epidemic proportions in the United States, and leftover medications are a primary source for nonmedical pain relievers. A past study at the University of Utah showed that micrographic surgeons were likely overprescribing opioids, with 35% of patients receiving a postoperative prescription. OBJECTIVE: To examine the current opioid prescribing habits of the micrographic surgeons at the University of Utah compared with those in 2010. METHODS: Retrospective chart review of the patient records of 4 micrographic surgeons between February and May 2017. RESULTS: Four hundred patient visits were reviewed. An opioid prescription was provided after 12% of encounters, 23% lower than in 2010 (p = .004). Younger patient age, increased number of stages and defect size, repair of the defect, and particular surgeons predicted opioid prescription. CONCLUSION: The percentage of patients who received an opioid prescription after undergoing micrographic surgery at the University of Utah decreased from 35% in 2010 to 12% in 2017. Reports of the minimal need of opioids after micrographic surgery, the authors' past study showing an institutional tendency to overprescribe, and reports of the national opioid epidemic likely all contributed to the decrease in opioid prescriptions at the authors' institution.

microRNA-1 Regulates Metabolic Flexibility in Skeletal Muscle via Pyruvate Metabolism.

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

Treatment-resistant atopic dermatitis: challenges and solutions.

Atopic dermatitis (AD) is a common, chronic, relapsing-remitting inflammatory disease that can be challenging to treat. Patients with mild disease are usually managed well with good skin care practices including moisturization and appropriate bathing along with intermittent use of topical therapies such as topical corticosteroids and/or topical calcineurin inhibitors during flares. Patients with frequent flares may benefit from proactive application of topical therapies twice a week to the most troublesome areas. Patients with severe disease often present significant treatment challenges. Systemic therapies are usually required for severe AD but have varying degrees of success and can be associated with side-effect profiles that require counseling and close monitoring. Phototherapy has been shown to have success in treating moderate-to-severe AD, but several factors can limit its utility and efficacy including cost and access. New therapies are in development targeting specific pathways relevant for AD. Dupilumab was the first biologic treatment approved in North America, Europe, and Japan for adults with moderate-to-severe AD. Although this treatment can lead to rapid improvement in the majority of patients, there are inadequate responders. In this review, we discuss the clinical challenges and treatment options for moderate-to-severe refractory AD.

Upfront Radiotherapy with Concurrent and Adjuvant Vismodegib Is Effective and Well-Tolerated in a Patient with Advanced, Multifocal Basal Cell Carcinoma.

We present a case report of a male with multifocal and extensive basal cell carcinoma. Due to extremely large size and deep tumor infiltration, he was not a surgical candidate. Combined modality treatment of fractionated radiation with concurrent vismodegib was chosen. Concurrent treatment was previously reported in the palliative and recurrent setting. This is the first case of concurrent vismodegib and radiation therapy for upfront definitive management. The patient experienced complete response in all treated lesions.