Characteristics of a transgender and gender-diverse patient population in Utah: Use of electronic health records to advance clinical and health equity research.

Transgender and gender-diverse (TGD) people, individuals whose gender identity differs from their sex assigned at birth, face unique challenges in accessing gender-affirming care and often experience disparities in a variety of health outcomes. Clinical research on TGD health is limited by a lack of standardization on how to best identify these individuals. The objective of this retrospective cohort analysis was to accurately identify and describe TGD adults and their use of gender-affirming care from 2003-2023 in a healthcare system in Utah, United States. International Classification of Disease (ICD)-9 and 10 codes and surgical procedure codes, along with sexual orientation and gender identity data were used to develop a dataset of 4,587 TGD adults. During this time frame, 2,985 adults received gender-affirming hormone therapy (GAHT) and/or gender-affirming surgery (GAS) within one healthcare system. There was no significant difference in race or ethnicity between TGD adults who received GAHT and/or GAS compared to TGD adults who did not receive such care. TGD adults who received GAHT and/or GAS were more likely to have commercial insurance coverage, and adults from rural communities were underrepresented. Patients seeking estradiol-based GAHT tended to be older than those seeking testosterone-based GAHT. The first GAS occurred in 2013, and uptake of GAS have doubled since 2018. This study provides a methodology to identify and examine TGD patients in other health systems and offers insights into emerging trends and access to gender-affirming care.

Toward more personalized breast cancer risk assessment: The polygenic risk score.

ABSTRACT: Healthcare providers often are uncertain about how best to assess and manage breast cancer risk. Women at average risk wonder when to start mammography and how often to go. Women at increased risk might inquire about genetic testing, MRI screening, and preventive measures. Patients who carry gene mutations face higher stakes and more complex risk management choices, but only some are aware of their status. This article helps clinicians stratify breast cancer risk and discusses a newer genomic test, the polygenic risk score, that may enable more personalized risk management and decision-making.

Use of a Feedback Survey as a Part of a Wellness Champions Program to Improve Academic Faculty Satisfaction and Burnout: Implications for Burnout in Academic Health Centers.

BACKGROUND: Faculty and trainee well-being at academic medical centers is a nationwide concern. In response, the University of Utah Health created a system-wide provider wellness program that used individual faculty champions who were empowered to 1) examine the unique needs of their department or division using a lens of quality improvement, 2) design projects to address well-being, and 3) measure impact of projects addressing well-being. One team used a feedback tool to attempt to improve the well-being of Family Medicine faculty by better understanding challenges and developing a roadmap for action. OBJECTIVE: Evaluate the effectiveness of an anonymous feedback tool on faculty well-being. METHODS: The Division of Family Medicine developed and implemented a quarterly anonymous faculty survey to facilitate an ongoing improvement process for faculty wellness in 2016. The faculty survey identified thematic concerns, which were used to develop constructive solutions and systemic changes. RESULTS: A closed loop feedback structure provided rich faculty input into impacts on burnout and professional well-being. Sense of control (good to optimal) over workload among faculty increased significantly (p = 0.011) from 10% to 42% over one year exhibiting a large effect size (Cohen's h = 0.751). Faculty burnout, using a single item emotional exhaustion question validated to the Maslach Burnout Inventory, was reduced from 48% to 25% showing a medium effect size (Cohen's h = 0.490 with p = 0.097). Work related stress was reduced from 72% to 50% demonstrating clinical significance (Cohen's h = 0.465) but not statistical significance (p = 0.154)-an effect which was more noticeable when comparing means between years (Cohen's d=0.451with p = 0.068). Response rate was 100% in 2016 (29/29) and 92% (23/25) in 2017. CONCLUSION: This faculty survey, which has since been adopted by other groups at the University of Utah, could help improve well-being in a variety of health care professions.

Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity.

Intestinal barrier function is reduced in inflammatory bowel disease (IBD). Tumor necrosis factor (TNF) and interleukin (IL)-13, which are up-regulated in IBD, induce barrier defects that are associated with myosin light chain kinase (MLCK) activation and increased claudin-2 expression, respectively, in cultured intestinal epithelial monolayers. Here we report that these independent signaling pathways have distinct effects on tight junction barrier properties and interact in vivo. MLCK activation alters size selectivity to enhance paracellular flux of uncharged macromolecules without affecting charge selectivity and can be rapidly reversed by MLCK inhibition. In contrast, IL-13-dependent claudin-2 expression increases paracellular cation flux in vitro and in vivo without altering tight junction size selectivity but is unaffected by MLCK inhibition in vitro. In vivo, MLCK activation increases paracellular flux of uncharged macromolecules and also triggers IL-13 expression, claudin-2 synthesis, and increased paracellular cation flux. We conclude that reversible, MLCK-dependent permeability increases cause mucosal immune activation that, in turn, feeds back on the tight junction to establish long-lasting barrier defects. Interactions between these otherwise distinct tight junction regulatory pathways may contribute to IBD pathogenesis.

Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a multifactorial disease thought to be caused by alterations in epithelial function, innate and adaptive immunity, and luminal microbiota. The specific role of epithelial barrier function remains undefined, although increased activity of intestinal epithelial myosin light chain kinase (MLCK), which is the primary mechanism of tumor necrosis factor-induced barrier dysfunction, occurs in human IBD. Our aim was to determine whether, in an intact epithelium, primary dysregulation of the intestinal epithelial barrier by pathophysiologically relevant mechanisms can contribute to development of colitis. METHODS: We developed transgenic (Tg) mice that express constitutively active MLCK (CA-MLCK) specifically within intestinal epithelia. Their physiology, immune status, and susceptibility to disease were assessed and compared with non-Tg littermate controls. RESULTS: CA-MLCK Tg mice demonstrated significant barrier loss but grew and gained weight normally and did not develop spontaneous disease. CA-MLCK Tg mice did, however, develop mucosal immune activation demonstrated by increased numbers of lamina propria CD4(+)lymphocytes, redistribution of CD11c+cells, increased production of interferon-gamma and tumor necrosis factor, as well as increased expression of epithelial major histocompatibility complex class I. When challenged with CD4+CD45+Rb(hi) lymphocytes, Tg mice developed an accelerated and more severe form of colitis and had shorter survival times than non-Tg littermates. CONCLUSIONS: Primary pathophysiologically relevant intestinal epithelial barrier dysfunction is insufficient to cause experimental intestinal disease but can broadly activate mucosal immune responses and accelerate the onset and severity of immune-mediated colitis.