Recent Publications by CFE Educators

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using and models, in combination with genetic lineage tracing and human tissue, we discover a SOX2 stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism.

OBJECTIVE

To compare major depression risk among young adults with juvenile-onset and adult-onset systemic lupus erythematosus (SLE), and to determine demographic and health-related predictors of depression.

METHODS

Young adults with SLE ages 18-45 years (n = 546) in the Lupus Outcomes Study completed annual telephone surveys from 2002-2015, including assessment of depression using the Center for Epidemiologic Studies Depression Scale (CES-D), and self-report measures of sociodemographics and health characteristics. Juvenile-onset SLE was defined as age 18 years at diagnosis (n = 115). Repeated-measures analysis was performed to assess the risk for major depression (CES-D ≥24) at any point in study, and logistic regression was used to assess for recurrent (present on ≥2 assessments) major depression.

RESULTS

Major depression was experienced by 47% of the cohort at least once during the 12-year study period. In adjusted analyses, juvenile-onset SLE patients had an increased risk of having a major depressive episode (odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.0-2.7]) and recurrent episodes (OR 2.2 [95% CI 1.2-4.3]), compared to participants with adult-onset SLE. Older age, lower educational attainment, and physical function, higher disease activity, and a history of smoking were associated with an increased depression risk. Juvenile-onset SLE patients had a higher risk of major depression across all educational groups.

CONCLUSION

Young adults with SLE, particularly those with juvenile-onset disease, are at high risk for major depression, which is associated with increased disease activity, poorer physical functioning, and lower educational attainment. Early depression intervention in young adults with SLE has the potential to improve both medical and psychosocial outcomes.

BACKGROUND

Heterozygous mutations in caspase recruitment domain family member 14 gene (CARD14) have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many subjects with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids, and tumor necrosis factor-α inhibitors.

OBJECTIVE

We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14.

METHODS

Subjects were referred for genetic testing as part of a registry of subjects with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed.

RESULTS

We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset; prominent involvement of the cheeks, chin, and ears; family history of psoriasis or PRP; minimal response to conventional topical and systemic psoriasis therapies; and improvement with ustekinumab.

LIMITATIONS

Relatively small sample size.

CONCLUSIONS

Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption to describe this spectrum of disease. Subjects with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.

An unprecedented number of medical students and residents express the desire to participate in global health work during their training and beyond. Preparing learners for work in underserved settings makes it more likely that they will continue to work in areas of need. Training programs that focus on global health have been criticized as there is ample work to be done in the US, and often global health work becomes learner-centric, which is difficult to maintain and potentially burdensome and harmful to the host site. In this article, we discuss a curriculum and training program that intentionally prepares learners to work responsibly and collaboratively in low-resource settings, both nationally and globally.

In 2013, National Immunization Survey-Teen data indicated that >40% of female adolescents had not initiated the human papillomavirus (HPV) vaccine series and >60% had not completed the series, documenting vaccination rates much lower than those for other vaccines recommended for adolescents. The Chicago Department of Public Health (CDPH) was 1 of 22 jurisdictions nationwide to receive a Prevention and Public Health Fund award through the Centers for Disease Control and Prevention to improve HPV vaccination rates among adolescents. The CDPH implemented 5 interventions targeting the public, clinicians and their staff, and diverse immunization and cancer prevention stakeholders. Compared with 2013 jurisdiction-specific HPV vaccination rates among all adolescents, Chicago's HPV vaccination rates were increased significantly in 2014 and 2015. This article details the methods and results of Chicago's successful interventions, the particular strengths as well as barriers encountered, and future steps necessary for sustaining improvement.

BACKGROUND

The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT.

METHODS

From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy.

RESULTS

A total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy.

CONCLUSION

Expectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations.

LEVEL OF EVIDENCE

Prognostic/epidemiologic study, level III; Therapeutic study, level IV.