Background Burnout is a complex syndrome of emotional distress that can disproportionately affect individuals who work in healthcare professions. Study Design For a national survey of burnout in US general surgery residents, we asked all Accreditation Council for Graduate Medical Education-accredited general surgery program directors to email their general surgery residents an invitation to complete an anonymous, online survey. Burnout was assessed with the Maslach Burnout Inventory; total scores for Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA) subscales were calculated. Burnout was defined as having a score in the highest tertile for EE or DP or lowest tertile for PA. Chi-square tests and one-way analyses of variance were used to test associations between burnout tertiles for each subscale and various resident and training-program characteristics as appropriate. Results From April–December, 2014, 665 residents actively engaged in clinical training had data for analysis; 69% met the criterion for burnout on at least one subscale. Higher burnout on each subscale was reported by residents planning private practice compared with academic careers. A greater proportion of women than men reported burnout on EE and PA. Higher burnout on EE and DP was associated with greater work hours per week. Having a structured mentoring program was associated with lower burnout on each subscale. Conclusions The high rates of burnout among general surgery residents are concerning given the potential impact of burnout on the quality of patient care. Efforts to identify at-risk populations and to design targeted interventions to mitigate burnout in surgical trainees are warranted.

IntroductionTargeted mAb-based therapies provide effective and safe treatments for hematologic malignancies. Rituximab, which specifically targets the B-cell antigen CD20, has had the greatest success, revolutionizing the treatment of the 2 most common forms of nonHodgkin lymphoma: follicular and diffuse large B-cell lymphoma. In addition, mAb-based therapies targeting CD52 (alemtuzumab) and CD33 (gemtuzumab ozogamicin) have been approved for the treatment of chronic lymphocytic leukemia and acute myelogenous leukemia, respectively. Despite the progress of these strategies, they do have limitations. Only a fraction of patients respond to rituximab, and the majority of those who do respond will eventually relapse. Treatment with alemtuzumab and gemtuzumab are limited by safety concerns, and many additional hematologic malignancies do not respond to treatment with any of these targeted therapies. Various therapies based on alternate mAbs, including second-generation anti-CD20 mAbs and those targeting alternate cell-surface proteins such as CD19, CD22, CD30, CD37, CD40, and CD74, have been developed and are at different stages of clinical testing in the hopes of providing approaches to treating a broader spectrum of hematologic malignancies that are poorly served by existing therapies. 1,2 Whereas targeting of cell-surface antigens themselves can mediate antitumor activity through the induction of apoptosis, most mAb-based activity against hematologic malignancies is reliant on either Fc-mediated effector functions such as complementdependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity 3,4 or is engineered through the conjugation of an immunotoxin or radiolabeled isotope. 1 Considering the potential of naturally occurring CTLs to mediate cell lysis, various strategies have also been explored to recruit CTLs to mediate tumor cell killing. Tumor-specific CTLs exert extremely potent effects through recognition of the corresponding peptide/MHC complex recognized by their TCR, and are among the most potent cells that mediate antitumor effects. A major limitation in generating tumorspecific CTLs in vivo is that their induction requires the use of vaccine strategies, such as dendritic cell-based vaccines, 5 that are capable of breaking tolerance to cancer self-antigens. One alternative is ex vivo expansion and activation of rare, tumor-specific CTLs for reinfusion into cancer patients. 6 However, cancer cells can down-regulate MHC expression as an escape mechanism, thus preventing the ability of CTLs to recognize their antigenic peptide. The genetic manipulation of patients' T cells to express chimeric antigen receptors comprising a tumor-specific antigen and T cellactivating properties before their adoptive transfer provides a non-MHC-restricted approach to targeting cancer, as was shown recently in the treatment of lymphoma with T cells engineered to recognize CD19. 7 However, the patient-specific manipulation and risk associated with this procedure represent major limitations to its expanded use. Alt...

No abstract

Current therapies for acute myeloid leukemia (AML) are largely ineffective, and AML patients may benefit from targeted immunotherapy approaches. MGD006 is a bispecific CD3xCD123 dual-affinity re-targeting (DART) molecule that binds T lymphocytes and cells expressing CD123, an antigen up-regulated in several hematological malignancies including AML. MGD006 mediates blast killing in AML samples, together with concomitant activation and expansion of residual T cells. MGD006 is designed to be rapidly cleared, and therefore requires continuous delivery. In a mouse model of continuous administration, MGD006 eliminated engrafted KG-1a cells (an AML-M0 line) in human PBMC (peripheral blood mononuclear cell)-reconstituted NSG/β2m(-/-) mice at doses as low as 0.5 μg/kg per day for ~7 days. MGD006 binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells. MGD006 was well tolerated in monkeys continuously infused with 0.1 μg/kg per day escalated weekly to up to 1 μg/kg per day during a 4-week period. Depletion of circulating CD123-positive cells was observed as early as 72 hours after treatment initiation and persisted throughout the infusion period. Cytokine release, observed after the first infusion, was reduced after subsequent administrations, even when the dose was escalated. T cells from animals with prolonged in vivo exposure exhibited unperturbed target cell lysis ex vivo, indicating no exhaustion. A transient decrease in red cell mass was observed, with no neutropenia or thrombocytopenia. These studies support clinical testing of MGD006 in hematological malignancies, including AML.

IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63–5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47–15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95–3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27–4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02–3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00–3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05–16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51–5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.