Nociceptive and Transcriptomic Responses in a Swine Diabetic Wound Model Treated With a Topical Angiotensin 1 Receptor Antagonist.

BACKGROUND: Painful, treatment-resistant wounds are prevalent among diabetic patients and significantly affect health-related quality of life (HRQOL). Topical treatments may help alleviate pain without risk of dependence or side effects. However, there is a lack of topical wound compounds targeting pain-specific receptors. One possible target is proinflammatory angiotensin 1 receptor (AT1R), which is upregulated in diabetic skin and has been implicated in nociception. OBJECTIVES: We investigated the effects of topical valsartan, an AT1R antagonist, on pain (nociceptive thresholds) and gene expression changes (transcriptomics) in a swine model of diabetic wounds. METHODS: Eight wounds were surgically induced in diabetic, hyperglycemic Yucatan miniature swine ( n = 4). Topical AT1R antagonist was applied to wounds on one side and vehicle on the other side. Nocifensive testing was conducted at baseline and then weekly, beginning 7 days after wound induction. Mechanical and thermal stimuli were applied to the wound margins until a nocifensive reaction was elicited or a predetermined cutoff was reached. After 7 weeks of testing, tissue from the dorsal horn, dorsal root ganglion, and wounds were sequenced and analyzed with DESeq2. Unbiased pathway analyses using Metascape were conducted on differentially expressed genes. RESULTS: There was no significant difference in mechanical tolerance threshold between AT1R antagonist-treated and vehicle-treated wounds ( p = .106). Thermal tolerance was significantly higher in AT1R antagonist-treated wounds compared to vehicle-treated ( p = .015). Analysis of differentially expressed genes revealed enriched pathways of interest: interleukin-18 signaling in dorsal horn laminae IV-V and sensory perception of mechanical stimulus in wound tissue. DISCUSSION: In this study, wounds modeling diabetic ulcers were created in hyperglycemic swine and treated with a topical AT1R antagonist. AT1R-antagonist-treated wounds had a higher tolerance threshold than vehicle-treated wounds for thermal hyperalgesia, but not mechanical allodynia. Pathway analyses of differentially expressed genes revealed several pathways of interest for future pain research. Although further studies are needed to confirm the findings, this study can improve nursing care by providing information about a potential future treatment that may be used to decrease pain and improve HRQOL in patients with diabetic wounds.

Targeted therapy use in adults with cancer ≥85 years of age.

PURPOSE: Assess patient- and clinical-related variables associated with targeted cancer treatments (TTs) for adults ≥85 years of age. RATIONALE: TTs have pathway-specific side effects that negatively affect QoL and medication adherence, which may reduce TT efficacy. Research has not focused on patients aged ≥85 years; therefore, the scope of TT use in this age group is not understood. METHODS: We conducted an electronic medical record review to identify individuals ≥85 years treated with TT. RESULTS: The sample (N = 295) was 53.5% male, 41% married/partnered, and 73.7% Caucasian. Common cancer types included breast (26.3%), prostate (31.3%), and leukemia (14.1%). Only one-third (n = 98) of the sample had TT side effects noted in their patient chart. CONCLUSIONS: Patients aged ≥85 years took similar TTs and experienced similar side effects as reported by research of younger patients; however, symptom experience was not well-reported.