Mendelian randomisation (MR) studies show that higher body mass index (BMI) and lower 25-hydroxyvitamin D (25[OH]D) increase psoriasis risk. The combined effect of these factors has not been explored using factorial MR. Using cross-sectional data from UK Biobank (UKB, n=398 404) and the Trøndelag Health Study (HUNT, n=86 648), we calculated polygenic risk scores for BMI and 25(OH)D to estimate odds ratios for psoriasis using 2x2 and continuous factorial MR. We quantified additive interaction by relative excess risk due to interaction (RERI)-estimates. We also performed traditional observational analyses in UKB. There were 12 207 (3.1%) participants with psoriasis in UKB and 7794 (9.0%) in HUNT. In 2x2 factorial MR, we found no evidence of relative excess risk for psoriasis due to interaction between genetically predicted higher BMI and lower 25(OH)D, neither in UKB (RERI -0.01, 95% confidence interval (CI) -0.08, 0.07) nor in HUNT (RERI -0.04, 95% CI -0.14, 0.06). The same was observed in the continuous factorial MR and observational analyses. In conclusion, this study did not find evidence of interaction between BMI and 25(OH)D on the risk of psoriasis. Given minor differences in measured BMI and 25(OH)D between the factorial groups, small effects may have been undetected.

Due to the increasingly high volume of cutaneous and percutaneous procedures performed annually, the demand for local anesthesia has steadily risen. The gold standard formulations for local anesthesia contain epinephrine at a concentration of 1:100,000 added to lidocaine to aid in hemostasis. Epinephrine, an α-agonist, also exhibits off-target β-adrenergic effects that carry risk of adverse events with these injections. Furthermore, the ongoing global shortage of epinephrine highlights the need for a safer and viable alternative. Midodrine, a targeted a1-adrenergic receptor agonist, is utilized as a vasopressor to induce arterial and venous vasoconstriction. We developed a formulation of 2% lidocaine combined with 1:2,000,000 epinephrine and 50uM midodrine (MLE formulation) hypothesizing that this combination would exhibit synergism on hemostasis. In a porcine model of blood loss following punch biopsies, our formulation was compared to 2% lidocaine, 2% lidocaine with 1:100,000 epinephrine, 2% lidocaine with 1:2,000,000 epinephrine, and 2% lidocaine with 50uM midodrine. Our results indicate that 2% lidocaine with 1:100,000 epinephrine and our MLE formulation were statistically comparable with both significantly reducing bleeding when compared to the 2% lidocaine (p < 0.05). 2% lidocaine with midodrine alone also showed additional promise as an effective hemostatic formulation. Thus, combination of low-concentration epinephrine and midodrine with lidocaine may exhibit synergistic hemostatic effect in cutaneous surgical settings while reducing potential off-target effects of either vasoconstrictor alone at higher concentrations as adjunct monotherapies.

Cancer survivors have an increased risk of developing second primary malignancies. We aimed to identify whether certain cancers lead to an increased risk of developing melanoma among cancer survivors. We evaluated the risk of developing cutaneous melanoma after the 20 most common cancers in the United States through the Surveillance, Epidemiology, and End Results database. We identified 9 primary cancers linked to increased risk of developing a subsequent cutaneous melanoma: cutaneous melanoma (standardized incidence ratio [SIR]= 9.65), leukemia (SIR= 1.76), non-Hodgkin lymphoma (SIR= 1.33), thyroid cancer (SIR= 1.32), brain and nervous system cancer (SIR= 1.31), myeloma (SIR= 1.23), breast cancer (SIR= 1.13), oral cavity/pharynx cancer (SIR= 1.12), and prostate cancer (SIR= 1.03). The risk of developing melanoma was highest 1-5 years after diagnosis of most primary cancers. Notably, individuals aged under 50 years with a prior melanoma had a 14-fold increased risk. Our findings highlight specific at-risk groups-such as those aged under 50 years with recent melanoma, individuals in their 60s diagnosed with leukemia, and those aged over 80 years with recent thyroid cancer-who may benefit from heightened clinical vigilance and tailored melanoma screening strategies.