Topical Ruxolitinib in the Treatment of Necrobiosis Lipoidica: A Prospective, Open-Label Study.

Necrobiosis lipoidica (NL) is a rare granulomatous disease. There are few effective treatments for NL. We sought to investigate the efficacy and safety of the Jak1/2 inhibitor, ruxolitnib, in the treatment of NL and identify the biomarkers associated with the disease and treatment response. We conducted an open-label, phase 2 study of ruxolitinib in 12 patients with NL. We performed transcriptomic analysis of tissue samples before and after treatment. At week 12, the mean NL lesion score decreased by 58.2% (SD = 28.7%, P = .003). Transcriptomic analysis demonstrated enrichment of type I and type II IFN pathways in baseline disease. Weighted gene coexpression network analysis demonstrated post-treatment changes in IFN pathways with key hub genes IFNG and signal transducer and activator of transcription 1 gene STAT1. Limitations include small sample size and a study group limited to patients with <10% body surface area. In conclusion, ruxolitinib is an effective treatment for NL and targets the key pathogenic mediators of the disease.

Oral Baricitinib in the Treatment of Cutaneous Lichen Planus.

Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.

Treatment of Hydroxyurea-Induced Ulcers With Timolol.

This report evaluates the use of timolol in 2 patients with long-term hydroxyurea use and lower-extremity ulcers resistant to other treatments.

Relationship Between Pain Management Modality and Return Rates for Lower Back Pain in the Emergency Department.

BACKGROUND: Emerging evidence suggests that opioid use for patients with acute low back pain does not improve functional outcomes and contributes to long-term opioid use. Little is known about the impact of opioid administration in the emergency department (ED) for patients with low back pain. OBJECTIVES: This study compares 30-day return rates after administration of various pain management modalities for emergency department (ED) patients with low back pain. METHODS: We conducted a retrospective multicenter observational study of patients in the ED who were diagnosed with low back pain and discharged home in 21 EDs between November 2018 and April 2020. Patients were categorized based on the pain management they received in the ED and compared with the reference group of patients receiving only nonsteroidal anti-inflammatory drugs, acetaminophen, or a combination of the two. The proportions of ED return visits within 30 d for each medication category was calculated and associations between analgesia categories and proportions of return visits were assessed using logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Patients with low back pain who received any opioid, intravenous opioid, or intramuscular opioid had significantly increased proportions of a return visit within 30 d (32% [OR 1.78 {95% CI 1.21-2.64}]; 33% [OR 1.83 {95% CI 1.18-2.86}]; and 39% [OR 2.38 {95% CI 1.35-4.12}], respectively) when compared with patients who received nonsteroidal anti-inflammatory drugs (19%), acetaminophen (20%), or a combination of the two (8%). CONCLUSIONS: Patients receiving opioids were more likely to return to the ED within 30 d than those receiving received nonsteroidal anti-inflammatory drugs or acetaminophen. This suggests that the use of opioids for low back pain in the ED may not be an effective strategy, and there may be an opportunity to appropriately treat more of these patients with nonopioid medications.

Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States.

BACKGROUND AND OBJECTIVES: With multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006-2008, 2009-2011, and 2012-2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post-dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH. RESULTS: Among 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol-based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol-based strategies at dialysis initiation decreased across cohorts: 15% (2006-2008) to 5% (2012-2015). The proportion with active vitamin D sterol-based strategies after 18 months of dialysis decreased across cohorts: 52% (2006-2008) to 34% (2012-2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006-2008 and 2009-2011 cohorts, and increased to two- to three-fold in the 2012-2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement. CONCLUSIONS: Over time, mineral metabolism management involved less use of vitamin D sterol-based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.