Clinically Recognized Depression and Mental Health Treatment in a Single Center Cohort of Patients with Systemic Sclerosis.

Introduction: In this study, we investigated the prevalence of depression, depression treatment, and symptom burden in patients with systemic sclerosis (SSc) and examined their associations with the center for epidemiologic studies depression scale revised (CESD-R) scores. Methods: The Prospective Registry in Scleroderma at Massachusetts General Hospital (PRISM) is a longitudinal registry of patients with SSc. Among participants with CESD-R score ≥ 16, indicating possible depression, a chart review was performed for mental health diagnoses and treatments. We examined the relation of demographic and clinical factors to the presence of mental health diagnoses or treatment using logistic regression. We evaluated the association of SSc symptoms and the COVID-19 pandemic with a CESD-R score using quantile regression. Results: Of 214 patients enrolled in PRISM, 129 participants (38% diffuse and 59% limited) completed at least one CESD-R questionnaire. In the first survey, 29% had possible depression (CESD - R ≥ 16) and 16% had probable depression (CESD - R ≥ 23). Of 20 participants with probable depression, 90% received treatment for a mood disorder. In a multivariable logistic regression model among participants with CESD - R ≥ 16, none of the evaluated variables (CESD-R score, age, gender, employment status, race, and ethnicity) was associated with mental health diagnosis or treatment. Higher baseline dyspnea index, modified Rodnan skin score, and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal total score and subscores were associated with higher CESD-R score. Conclusion: In this single-center cross-sectional study, 16% of participants had significant depressive symptoms. Dyspnea, extent of skin involvement, and gastrointestinal symptoms were associated with depression symptoms.

Incorporating Telemedicine in Rheumatology Fellowship Training Programs: Needs Assessment, Curricular Intervention, and Evaluation.

OBJECTIVE: To increase the confidence of rheumatology fellows in training (FITs) in delivering virtual care (VC) and prepare them for independent practice, we developed educational materials addressing gaps in their skills. METHODS: We identified gaps in telemedicine skills based on FIT performance in a virtual rheumatology objective structured clinical examination (vROSCE) station on VC delivery using video teleconference technology and survey (survey 1) responses. We created educational materials including videos of "mediocre" and "excellent" VC examples, discussion/reflection questions, and a document summarizing key practices. We measured change in the confidence levels of FITs for delivering VC with a post-intervention survey (survey 2). RESULTS: Thirty-seven FITs (19 first-year, 18 second- plus third-year fellows) from 7 rheumatology fellowship training programs participated in a vROSCE and demonstrated gaps in skills mapping to several Rheumatology Telehealth Competency domains. Confidence levels of FITs improved significantly from survey 1 to survey 2 for 22 of 34 (65%) questions. All participating FITs found the educational materials helpful for learning and reflecting on their own VC practice; 18 FITs (64%) qualified usefulness as "moderately" or "a lot." Through surveying, 17 FITs (61%) reported implementing skills from the instructional videos into VC visits. CONCLUSION: Continually assessing our learners' needs and creating educational materials addressing gaps in training are requisite. Using a vROSCE station, needs assessments, and targeted learning with videos and discussion-guidance materials enhanced the confidence level of FITs in VC delivery. It is imperative to incorporate VC delivery into fellowship training program curricula to ensure breadth in skills, attitudes, and knowledge of new entrants into the rheumatology workforce.

GFI1 Cooperates with IKZF1/IKAROS to Activate Gene Expression in T-cell Acute Lymphoblastic Leukemia.

Growth factor independence-1 (GFI1) is a transcriptional repressor and master regulator of normal and malignant hematopoiesis. Repression by GFI1 is attributable to recruitment of LSD1-containing protein complexes via its SNAG domain. However, the full complement of GFI1 partners in transcriptional control is not known. We show that in T-acute lymphoblastic leukemia (ALL) cells, GFI1 and IKAROS are transcriptional partners that co-occupy regulatory regions of hallmark T-cell development genes. Transcriptional profiling reveals a subset of genes directly transactivated through the GFI1-IKAROS partnership. Among these is NOTCH3, a key factor in T-ALL pathogenesis. Surprisingly, NOTCH3 expression by GFI1 and IKAROS requires the GFI1 SNAG domain but occurs independent of SNAG-LSD1 binding. GFI1 variants deficient in LSD1 binding fail to activate NOTCH3, but conversely, small molecules that disrupt the SNAG-LSD1 interaction while leaving the SNAG primary structure intact stimulate NOTCH3 expression. These results identify a noncanonical transcriptional control mechanism in T-ALL which supports GFI1-mediated transactivation in partnership with IKAROS and suggest competition between LSD1-containing repressive complexes and others favoring transactivation. IMPLICATIONS: Combinatorial diversity and cooperation between DNA binding proteins and complexes assembled by them can direct context-dependent transcriptional outputs to control cell fate and may offer new insights for therapeutic targeting in cancer.