Fully murine CD105-targeted CAR-T cells provide an immunocompetent model for CAR-T cell biology.

The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models. However, there are many advantages in studying CAR-T cell biology in an immunocompetent setting. We generated a fully murine CAR targeting CD105 (endoglin), a component of the TGFß receptor expressed on the surface of certain solid tumors and acute leukemias. CD105-targeted CAR-T cells can be grown from various murine backgrounds, tracked in vivo by congenic marks, and be activated by CD105 in isolation or expressed by tumor cells. CD105-targeted CAR-T cells were toxic at higher doses but proved safe in lower doses and modestly effective in treating wild-type B16 melanoma-bearing mice. CAR-T cells infiltrating the tumor expressed high levels of exhaustion markers and exhibited metabolic insufficiencies. We also generated a human CD105 CAR, which was efficacious in treating human melanoma and acute myeloid leukemia in vivo. Our work details a new murine model of CAR-T cell therapy that can be used from immunologists to further our understanding of CAR-T cell biology. We also set the foundation for further exploration of CD105 as a possible human CAR-T cell target.

Effective Goals-of-Care Conversations: From Skills Training to Bedside.

Introduction: Goals-of-care (GOC) conversations are essential to ensure high-quality care for people with serious illness. We developed a simulation experience to train internal medicine residents in GOC conversations near end of life, followed by a real-life GOC conversation as a Mini-Clinical Evaluation Exercise (Mini-CEX) including direct feedback from participating patients. Methods: The 3-hour simulation session trained teams of two learners each to interact with standardized patients portraying a patient with end-stage heart failure and an accompanying family member. Residents completed pre- and postsurveys regarding their self-assessed abilities and confidence in conducting these conversations. Piloted in 2016, the Mini-CEX was completed in 2017 with 28 residents 3-9 months after simulation. Patients and participating family members were invited to complete an optional, deidentified survey of their experience. Results: From 2015 to 2017, 84 residents completed simulation training. Ninety percent of postsurvey responders felt more prepared to conduct GOC conversations after simulation compared to 42% before training. Eighty percent or more reported confidence in discussing GOC (previously 67%), prognosis (previously 62%), and hospice (previously 49%). Analysis of Mini-CEX scores revealed that the majority of residents' skills were the same or improved compared with their performance in simulation; more than 70% demonstrated improvement in ensuring patients' comfort, displaying empathy, and recognizing/responding to emotion. Almost all patients and families reported feeling heard and satisfied with their conversation with the resident. Discussion: This curriculum was well received, and initial data support its effectiveness in enhancing residents' self-perceived confidence and interpersonal skills in real-world patient encounters.

Applying patient perspectives on caring to curriculum development.

OBJECTIVE: To report how patient viewpoints on caring inform curriculum development for teaching sessions on delivering bad news, making the transition to palliative care, and communicating about a medical error. METHODS: We conducted focus groups that used patients recruited from the surrounding community to view videotapes of physicians delivering bad news, talking with a patient about palliative care, and communicating about a medical error. We used focus group results, combined with evidence from the medical literature to inform curriculum content for workshops conducted with Internal Medicine and Family Medicine residents at the University of Massachusetts Medical School. RESULTS: Patient perspectives on caring gathered through focus groups differed in significant ways from the existing medical literature on caring when providers are communicating in the challenging situations that were depicted. Our data pointed out that individual reactions were unique and sometimes contradictory in that one person saw behavior as caring that others thought was uncaring. Participants often used qualifiers in their comments like "appropriate" amounts of information, "measured" empathy, chooses words carefully to reflect the relative nature of caring. "Arranges to meet healthcare needs," an issue that extends beyond the encounter, was seen as a new component of caring not previously described. Applying these concepts to curriculum required that we not only focus on the behavioral skills involved in these tasks, but also the processes of assessing patient's informational and emotional needs, and then taking steps to meet them, while adjusting behavior in real time to meet patients needs for caring. Workshops delivered were highly evaluated by residents. CONCLUSION: Patient perspectives on caring when providers deliver bad news, discuss transitions to palliative care, and communicate about a medical error reinforce that patient expectations for caring are highly contextualized and physician behavior needs to be individualized. We taught residents not only behavioral skills, but also the process skills of anticipating patient reactions, recognizing patient clues, planning and choosing effective strategies on the fly, and assessing one's own performance characteristic of communication expertise. PRACTICE IMPLICATIONS: Teaching caring attitudes with challenging communication tasks requires that learners appreciate and value not only caring behaviors but also learn the process by which they must adjust and titrate their actions to meet patient needs.

How patients perceive a doctor's caring attitude.

OBJECTIVE: Caring is closely associated with reduced malpractice litigation, adherence to treatment and even symptom relief. Caring also is included in pay for performance formulas as well as widely utilized for quality improvement purposes. Our objective in this prospective qualitative study was to define caring behaviors associated with three challenging encounters: discussing the transition from curative to palliative care, delivering bad news (cancer), and discussing a medical error (misplaced test result). The purpose was to lay the groundwork for the creation of a 'patient-centered' caring attitude checklist that could help the healthcare provider understand and ultimately enhance the patient's experience of care. METHODS: Groups of randomly selected lay people, henceforth referred to as patients: (1) engaged in 'think aloud' exercises to help create a 15-item caring behavior checklist; (2) used the checklist to rate videotapes of simulated challenging encounters conducted by twenty primary care physicians (total of 600 ratings sets); and (3) participated in 12 separate 1.5 h focus groups discussing the caring (and non-caring) behaviors exhibited in videotapes of the highest and lowest rated encounters. RESULTS: Thirteen behaviors emerged as focal for describing a doctor's caring attitude but with disagreement as to whether specific examples of these behaviors were 'caring' or 'uncaring.' For example, although the concept of empathic inquiry was considered important by most patients, the physician question, "Is there someone you can call or talk with" (about a cancer diagnosis) was interpreted by one patient as 'very caring' while another was 'impressed with how uncaring' the statement appeared. CONCLUSION: At the conceptual level there is a set of behaviors that represent caring, however, the manifestation of these behaviors is 'in the eye of the beholder.' The most important element of caring may not be the set of behaviors but a set of underlying abilities that include taking the patient's perspective and reflecting on the patient's responses. PRACTICE IMPLICATIONS: Medical education must focus on the underlying abilities of caring.

Primary care renewal: regional faculty development and organizational change.

BACKGROUND: Many reports, including the Future of Family Medicine, have called for change in primary care, but few have defined, implemented, and evaluated mechanisms to address such change. The regional, interdisciplinary Primary Care Renewal Project was designed to address problems in primary care practice and teaching related to practice management, compensation, increasing responsibility for teaching, and faculty development. METHODS: Twelve northeastern US medical schools assembled a conference attended by teams of key stakeholders representing both clinical and educational missions. Teams developed and implemented an institutional plan to address identified needs. Outcome data was collected during, and for 1 year after, the conference. RESULTS: Findings demonstrate novel ways of improving learning experiences, coordinating and centralizing planning efforts, and addressing faculty needs. The magnitude of organizational change ranged from establishing new administrative units with significant institutional authority (eg, restructuring dean's office) to enhancing the strategic planning process and refining mission statements to reflect emphasis on primary care. CONCLUSIONS: A well-planned, regional interdisciplinary effort that fosters the development of concrete plans can be associated with significant change in medical education. A central theme emerged--that primary care medicine will survive only if institutions align their educational and clinical missions and foster system-wide change.

Expert communication training for providers in community health centers.

BACKGROUND: Community health center (CHC) clinicians describe significant challenges in delivering care for populations with complex health needs. INTERVENTION: A three-workshop series was presented to 102 providers working in CHCs. Training focused on four areas identified through online needs assessment: challenging interactions; patient perspective; health literacy; and motivational interviewing. EVALUATION METHODS: A retrospective pre-post evaluation measured self-perceived change in content knowledge in all four areas. Participants documented commitments to change behaviors across workshops, which were analyzed for recurring themes. RESULTS: Paired t-tests documented improvement in all four content areas. Content analysis of commitments yielded four themes: empowering patients, structuring care, understanding patients, and reflecting purposefully. Of the sixty-eight percent of participants responding to post-workshop queries about their commitments (n=70), 94% report having fully implemented changes in practice behavior or planning to do so. CONCLUSIONS: Providers at CHCs benefit from opportunities to learn and reflect together about communication challenges in practice.

Initial testing of an instrument to measure teacher identity in physicians.

BACKGROUND: A previous study described 7 elements of teacher identity: intrinsic satisfaction from teaching, knowledge and skill about teaching, belonging to a community of teachers, receiving rewards for teaching, believing that being a doctor means being a teacher, feeling a responsibility to teach, and sharing clinical expertise. PURPOSE: To conduct the initial testing of an instrument to measure the 7 elements of teacher identity in clinical educators and to consider the potential applications of such an instrument. METHODS: A 37-item questionnaire was mailed to 153 preceptors of preclinical students. Categories reflected the elements of teacher identity listed here. Demographic data were collected. Means, alphas, ANOVAs, and paired t tests were calculated. RESULTS: Of 153 preceptors, 127 (83%) completed the questionnaire. Cronbach's alpha for the overall scale and several subscales were high. Salaried physicians and those who had completed a faculty development program scored significantly higher on several subscales than physicians who volunteered to teach or who did not have faculty development. CONCLUSIONS: This study provides preliminary evidence that teacher identity can be measured and that preceptors do not respond as a homogeneous group. Assessing teacher identity may be helpful to medical schools looking to identify and support physicians who teach.