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Small-cell lung cancer and other aggressive neuroendocrine cancers are often associated with early dissemination and frequent metastases. We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosinrelated kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.bHLH | SCLC

The treatment paradigm for patients with advanced non–small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non–small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti–vascular endothelial growth factor drugs. This article will review landmark studies that have led to U.S. Food and Drug Administration approval of immunotherapy agents alone or in combination with chemotherapy or other immunotherapy drugs to treat advanced non–small cell lung cancer.

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BackgroundThe importance of effective team leadership for achieving surgical excellence is widely accepted, but we understand less about the behaviors that achieve this goal. We studied cardiac surgical teams to identify leadership behaviors that best support surgical teamwork.MethodsWe observed, surveyed, and interviewed cardiac surgical teams, including 7 surgeons and 116 team members, from September 2013 to April 2015. We documented 1,926 surgeon/team member interactions during 22 cases, coded them by behavior type and valence (ie, positive/negative/neutral), and characterized them by leadership function (conductor, elucidator, delegator, engagement facilitator, tone setter, being human, and safe space maker) to create a novel framework of surgical leadership derived from direct observation. We surveyed nonsurgeon team members about their perceptions of individual surgeon's leadership effectiveness on a 7-point Likert scale and correlated survey measures with individual surgeon profiles created by calculating percentage of behavior types, leader functions, and valence.ResultsSurgeon leadership was rated by nonsurgeons from 4.2 to 6.2 (mean, 5.4). Among the 33 types of behaviors observed, most interactions constituted elucidating (24%) and tone setting (20%). Overall, 66% of interactions (range, 43%–84%) were positive and 11% (range, 1%–45%) were negative. The percentage of positive and negative behaviors correlated strongly (r = 0.85 for positive and r = 0.75 for negative, p < 0.05) with nonsurgeon evaluations of leadership. Facilitating engagement related most positively (r = 0.80; p = 0.03), and negative forms of elucidating, ie, criticism, related most negatively (r = –0.81; p = 0.03).ConclusionsWe identified 7 surgeon leadership functions and related behaviors that impact perceptions of leadership. These observations suggest actionable opportunities to improve team leadership behavior.

Lack of correlation across measures suggests either that inpatient psychiatric care quality is multidimensional or that it is unreliably assessed. Hospital ownership strongly predicted performance, and VA hospitals performed relatively poorly across most measures.

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