Citations

Purpose To determine baseline individual and school-related factors associated with increased risk of developing depression symptoms by year four (Y4) of medical school, and to develop a prognostic index that stratifies risk of developing depression symptoms (Depression-PI) among medical students. Method The authors analyzed data from 3,743 students (79% of 4,732) attending 49 U.S. medical schools who completed baseline (2010) and Y4 (2014) surveys. Surveys included validated scales measuring depression, stress, coping, and social support. The authors collected demographics and school characteristics and conducted multivariate analysis to identify baseline factors independently associated with Y4 depression symptoms. They used these factors to create a prognostic index for developing depression. They randomly divided the data into discovery (n = 2,455) and replication (n = 1,288) datasets and calculated c statistics ( c ). Results The authors identified eight independent prognostic factors for experiencing depression symptoms during training within the discovery dataset: age; race; ethnicity; tuition; and baseline depression symptoms, stress, coping behaviors, and social support. The Depression-PI stratified four risk groups. Compared with the low risk group, those in the intermediate, high, and very high risk groups had an odds ratio of developing depression of, respectively, 1.75, 3.98, and 9.19 ( c = 0.71). The replication dataset confirmed the risk groups. Conclusions Demographics; tuition; and baseline depression symptoms, stress, coping behaviors, and social support are independently associated with risk of developing depression during training among U.S. medical students. By stratifying students into four risk groups, the Depression-PI may allow for a tiered primary prevention approach.

Abstract Introduction: CLL phenotype (CD5+CD23+CD20dim) MBL is present in 5-10% of the general population. The prevalence and outcomes of adults with non-CLL like MBL (including CD5+CD23-, CD5+CD20bright, and CD5-) are not known. We screened for MBL using highly sensitive flow-cytometry in a clinic-based cohort of adults from the Mayo Clinic Biobank. Methods: The Mayo Clinic Biobank is a large scale bio-repository of 50,000 adults seen in primary care-based clinics. Herein, we focused on those adults ≥40 years who had stored peripheral blood mononuclear cells available (10% of the overall cohort). We screened for MBL using an 8 color (CD38, CD45, Kappa, Lambda, CD19, CD23, CD5 and CD20) flow cytometry assay validated to detect clonal B-cell events to the 0.005% level (1/20,000 events). Chi-square tests were used to assess associations with demographic characteristics. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for death. Results: A total of 2594 adults were screened; their median age was 63 years (range, 40-96) and 1111 (43%) were male. 2445/2594 (94%) individuals had interpretable flow cytometry results. A total of 336 (14%) individuals had MBL identified, of whom 276 (82%) had CLL-like MBL and 60 (18%) had non-CLL like MBL (including 39 adults with CD5- and 21 with CD5+CD23- or CD5+CD20 bright phenotype). A strong association between age and the prevalence of non-CLL like MBL was observed, with 0/278 (0%) in 40-49 years, 6/613 (1%) in 50-59 years, 20/674 (3%) in 60-69 years, 21/490 (4%) in 70-79 years, and 13/114 (11%) ≥80 years demonstrating non-CLL like MBL (p<0.001). Non-CLL like MBL was more common in men compared to women (5% vs. 1%; p<0.001). Compared to adults with no MBL, a higher proportion of non-CLL like MBL had a first-degree relative with a lymphoproliferative disorder (8% vs. 17%; p=0.03), and prior non-hematologic cancer (22% vs. 38%, p=0.006). The remainder of the present analysis is focused on adults with non-CLL like MBL (n=60). After a median follow-up of 5 years (range 0-8 years), 3/60 (5%) adults with non-CLL like MBL developed a hematologic malignancy (one myelodysplastic syndrome, two mantle cell lymphoma) compared to 5/2109 (0.2%) adults with no MBL (two large cell lymphoma, one multiple myeloma, one acute myeloid leukemia, one myelofibrosis). Among adults with non-CLL like MBL, the estimated 7-year overall survival (OS) was 79% compared to 94% in those with no MBL (p<0.001, HR for death 3.8, 95% CI 1.98-7.3). After adjusting for age, sex, and self-reported prior non-hematologic cancer, the HR for death was 1.50 (95% CI 0.74-3.05, p=0.26). Conclusion: In this large study, ~1 of 40 adults seen in a primary care setting had non-CLL like MBL. The prevalence of the non-CLL phenotype MBL increased with age. With current follow-up, the risk of progression to an overt lymphoproliferative neoplasm appears to be low. Citation Format: Sameer A. Parikh, Sara J. Achenbach, Kari G. Chaffee, Neil E. Kay, Connie E. Lesnick, James R. Cerhan, Curtis A. Hanson, Tait D. Shanafelt, Susan L. Slager. The prevalence of non-chronic lymphocytic leukemia (CLL) phenotype monoclonal B-cell lymphocytosis (MBL) in a population-based cohort of U.S. adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3256.

SummaryThe effects of ibrutinib on the natural history of autoimmune cytopenias (AIC) among chronic lymphocytic leukaemia (CLL) patients treated in routine clinical practice require further investigation. Using the Mayo Clinical CLL Database, 193 CLL patients treated with ibrutinib between November 2013 and January 2017 outside the context of a clinical trial were identified; complete review of their medical records was performed for details of past history of AIC and treatment‐emergent AIC. We identified 29/193 (15%) patients with history of AIC prior to ibrutinib start. Of 12 patients requiring AIC therapy at ibrutinib start, 8 (67%) were able to discontinue or de‐escalate AIC treatment, and no patient had worsening of their AIC after initiating ibrutinib. Eleven (6%) patients developed treatment‐emergent AIC after a median of 59 (range, 6–319) days following the initiation of ibrutinib, 7 of whom (64%) were able to continue ibrutinib. Overall and event‐free survival from time of ibrutinib start were not significantly different between patients with history of AIC and those with no history of AIC. Treatment‐emergent AIC were seen exclusively in patients with unmutated IGHV and were associated with a shorter EFS. These results suggest a low rate of treatment‐emergent AIC and improvement in patients with existing AIC.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT. We evaluated PD-1 and PD-L1 expression by immunohistochemistry in 39 CLL/SLL, 15 DLBCL-RT, and 26 other DLBCL. In CLL/SLL, neoplastic B-cell PD-1 expression was weak and restricted to prolymphocytes/paraimmunoblasts within proliferation centers (PCs) and accentuated PCs of all sizes. Neoplastic B-cell PD-1 expression was highly prevalent and demonstrated increased intensity in DLBCL-RT, but in contrast was only rarely seen in other DLBCL (12/15 vs. 1/26; P<0.0001). An excellent correlation (90% concordance) was observed between neoplastic B-cell PD-1 immunohistochemistry positivity and molecularly defined CLL/SLL clonal relatedness in DLBCL-RT. PD-L1 expression was observed on the neoplastic B cells in rare DLBCL-RT and other DLBCL cases (1/15 vs. 1/26; P>0.05) as well as background histiocytes and dendritic cells. Overall survival of DLBCL-RT was significantly inferior to that of the other DLBCL (median, 16.9 vs. 106.1 mo; P=0.002). Our findings suggest a biological continuum from prolymphocytes/paraimmunoblasts in CLL/SLL PCs to the neoplastic B-cells in DLBCL-RT. The characteristic PD-1 expression in DLBCL-RT makes it a potential surrogate marker for determining clonal relatedness to CLL/SLL, which may have important prognostic and therapeutic implications.

Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.

Abstract Physician burnout, a work‐related syndrome involving emotional exhaustion, depersonalization and a sense of reduced personal accomplishment, is prevalent internationally. Rates of burnout symptoms that have been associated with adverse effects on patients, the healthcare workforce, costs and physician health exceed 50% in studies of both physicians‐in‐training and practicing physicians. This problem represents a public health crisis with negative impacts on individual physicians, patients and healthcare organizations and systems. Drivers of this epidemic are largely rooted within healthcare organizations and systems and include excessive workloads, inefficient work processes, clerical burdens, work–home conflicts, lack of input or control for physicians with respect to issues affecting their work lives, organizational support structures and leadership culture. Individual physician‐level factors also play a role, with higher rates of burnout commonly reported in female and younger physicians. Effective solutions align with these drivers. For example, organizational efforts such as locally developed practice modifications and increased support for clinical work have demonstrated benefits in reducing burnout. Individually focused solutions such as mindfulness‐based stress reduction and small‐group programmes to promote community, connectedness and meaning have also been shown to be effective. Regardless of the specific approach taken, the problem of physician burnout is best addressed when viewed as a shared responsibility of both healthcare systems and individual physicians. Although our understanding of physician burnout has advanced considerably in recent years, many gaps in our knowledge remain. Longitudinal studies of burnout's effects and the impact of interventions on both burnout and its effects are needed, as are studies of effective solutions implemented in combination. For medicine to fulfil its mission for patients and for public health, all stakeholders in healthcare delivery must work together to develop and implement effective remedies for physician burnout.