β-adrenoceptor (β-AR) agonists are known to antagonize thrombin-induced impairment (TII) of bovine and ovine lung endothelial barrier function. The effects of adrenoceptor agonists and other vasoactive agents on human lung microvascular endothelial cell (HULEC-5a) barrier function upon thrombin exposure have not been studied. Furthermore, it is unknown whether the in vitro effects of adrenoceptor agonists translate to lung protective effects in vivo. We observed that epinephrine, norepinephrine, and phenylephrine enhanced normal and prevented TII of HULEC-5a barrier function. Arginine vasopressin and angiotensin II were ineffective. α_1B-, α_2A/B-, and β_1/2-ARs were detectable in HULEC-5a by RT-PCR. Propranolol but not doxazosin blocked the effects of all adrenoceptor agonists. Phenylephrine stimulated β₂-AR-mediated Gαs activation with 13-fold lower potency than epinephrine. The EC₅₀ to inhibit TII of HULEC-5a barrier function was 1.8 ± 1.9 nM for epinephrine and >100 nM for phenylephrine. After hemorrhagic shock and fluid resuscitation in rats, Evans blue extravasation into the lung increased threefold (p < 0.01 vs. sham). Single low-dose (1.8 μg/kg) epinephrine administration at the beginning of resuscitation had no effects on blood pressure and reduced Evans blue extravasation by 60% (p < 0.05 vs. vehicle). Our findings confirm the effects of β-adrenoceptor agonists in HULEC-5a and suggest that low-dose β-adrenoceptor agonist treatment protects lung vascular barrier function after traumatic hemorrhagic shock.

Roughly 100,000 new cases of melanoma are diagnosed yearly in the United States, the majority of which are early-stage disease with excellent prognosis. However, a subset of patients harbors clinically occult aggressive biology that can go undetected on standard clinicopathologic analyses. Gene expression profiling (GEP) assays have emerged as molecular adjuncts to risk stratification, aiming to improve sentinel lymph node biopsy (SLNB) decision-making and surveillance planning. Two commercial tests are widely available: the 31-gene expression profile (31-GEP, DecisionDx-Melanoma, Castle Biosciences) and the clinicopathologic gene expression profile (CP-GEP, Merlin, SkylineDx). This review summarizes the current evidence for each assay regarding their performance and utility, with a focus on potentially actionable use cases, limitations, and the practical context in which these tools are most valuable.