Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Substance-Related Found-Down Compartment Syndrome: A Systematic Review.

OBJECTIVE: To characterize the patient population with substance-related found-down extremity compartment syndrome (FDECS) and report on their treatment and outcome. DATA SOURCE: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles in English language were identified by searching 3 online databases, EMBASE, PubMed Publisher, and Cochrane Central, in September 2019. STUDY SELECTION: Studies involving substance-related FDECS were included. Exclusion criteria were as follows: patient age <18 years, not original studies, no full text available, technical reports, traumatic acute extremity compartment syndrome, chronic exertional compartment syndrome, and vascular acute extremity compartment syndrome. DATA EXTRACTION: There were 61 studies included with 166 cases of FDECS. Two investigators screened and extracted data independently according to a standardized template. Disagreements were addressed by an attempt to reach a consensus, and involvement of a third reviewer. Studies were quality assessed with "Quality Assessment tool for Case Series Studies." DATA SYNTHESIS: Descriptive statistics were reported using Excel. CONCLUSION: Substance-related FDECS is often occurring in young adults. Data from this review found that most of the patients were already diagnosed with substance use disorders and/or psychiatric disorders. There should be a high index of suspicion of FDECS in patients presenting after prolonged immobilization. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.