Anti-Tumor Necrosis Factor Alpha Therapeutic Drug Monitoring in Inflammatory Disease: A Systematic Review.

BACKGROUND: Monoclonal antibodies encompass an increasingly important treatment for a variety of dermatologic conditions including hidradenitis suppurativa (HS). The high failure rate and cost of anti-tumor necrosis alpha (TNF-α) agents and emergence of biologic treatments critically warrant treatment strategies that identify treatment failures early and optimize therapy. This review’s primary objective is to understand the current literature on biologic therapeutic drug monitoring (TDM) used in chronic inflammatory diseases and apply this knowledge to future dermatologic studies and treatment. METHODS: Randomized controlled trials (RCTs) or high-quality retrospective analyses of RCTs investigating the outcomes of biologic TDM were identified between January 1979 and January 2020 within the PubMed/MEDLINE database using keywords: "biologic," "therapeutic drug monitoring," and "randomized controlled trial," combined with common medical conditions for which biologics are prescribed: "rheumatoid arthritis," "inflammatory bowel disease," "psoriasis," "Crohn’s," "ulcerative colitis," "vasculitis," and "hidradenitis suppurativa." The methods and findings of each study were compared. RESULTS: Three RCTs were included all examining TDM of TNF-α inhibitors in inflammatory bowel disease (IBD). Two studied TDM of infliximab, and one adalimumab. An additional high-quality retrospective analysis of an infliximab RCT captured in our search was also included. Two of the three RCTs (TAXIT and PAILOT) found proactive TDM superior to clinically based dosing and reactive TDM, respectively. The third RCT (TAILORX) found no significant difference between proactive and reactive TDM. CONCLUSION: TDM of anti-TNF-α biologics in IBD has demonstrated success through RCTs. Knowledge gained from these studies applies to dermatologic treatment. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6671.

Functional Imaging in Wounds: Imaging Modalities of Today and Tomorrow.

Wound care is a multidisciplinary field with significant economic burden to our healthcare system. Not only does wound care cost the US healthcare system $20 billion annually, but wounds also remarkably impact the quality of life of patients; wounds pose significant risk of mortality, as the five-year mortality rate for diabetic foot ulcers (DFUs) and ischemic ulcers is notably higher compared to commonly encountered cancers such as breast and prostate. Although it is important to measure how wounds may or may not be improving over time, the only relative "marker" for this is wound area measurement-area measurements can help providers determine if a wound is on a healing or non-healing trajectory. Because wound area measurements are currently the only readily available "gold standard" for predicting healing outcomes, there is a pressing need to understand how other relative biomarkers may play a role in wound healing. Currently, wound care centers across the nation employ various techniques to obtain wound area measurements; length and width of a wound can be measured with a ruler, but this carries a high amount of inter- and intrapersonal error as well as uncertainty. Acetate tracings could be used to limit the amount of error but do not account for depth, thereby making them inaccurate. Here, we discuss current imaging modalities and how they can serve to accurately measure wound size and serve as useful adjuncts in wound assessment. Moreover, new imaging modalities are also discussed and how up-and-coming technologies can provide important information on "biomarkers" for wound healing.

The human heart contains distinct macrophage subsets with divergent origins and functions.

Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.