Earning Patient Trust: More Than a Question of Signaling

Laura Specker Sullivan's article “Trust, Risk, and Race in American Medicine” is a philosophically grounded and highly practical call for medical professionals to take on the task of comprehending the sources of patients’ mistrust. This is not only a clinical competence but also a moral obligation, in particular, when mistrust is warranted—as with African American patients who rely on medical institutions that have breached and continue to breach the trust of their communities. While Specker Sullivan focuses on how clinicians can signal comprehension once it has already been attained, I wish to step back and examine the nature of the efforts to gain knowledge. The effort to comprehend requires, at a minimum, the following actions: educating oneself about medical racism, examining one's implicit biases, and engaging, with empathic curiosity, with the patient or family members in the clinical encounter at hand.     

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

BackgroundDiffuse midline glioma, formerly DIPG (diffuse intrinsic pontine glioma), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated (i) whether direct delivery of adenovirus-expressing cluster of differentiation (CD)40 ligand (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and (ii) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.MethodsSyngeneic gliomas in the brainstems of immunocompetent mice were treated with Ad-CD40L and survival, toxicity, and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient–derived diffuse midline gliomas and immunocompetent models.ResultsExpression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intratumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-sequencing analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with interleukin (IL)-6, IL-1β, and tumor necrosis factor α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for diffuse midline gliomas. Direct intratumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity.ConclusionsVirus-mediated delivery of CD40L has the potential to be effective in treating diffuse midline gliomas without obligatory neuroinflammation-associated toxicity.     

A multi-source feedback tool for measuring a subset of Pediatrics Milestones

Background: The Pediatrics Milestones Assessment Pilot employed a new multisource feedback (MSF) instrument to assess nine Pediatrics Milestones among interns and subinterns in the inpatient context.

Objective: To report validity evidence for the MSF tool for informing milestone classification decisions.

Methods: We obtained MSF instruments by different raters per learner per rotation. We present evidence for validity based on the unified validity framework.

Results: One hundred and ninety two interns and 41 subinterns at 18 Pediatrics residency programs received a total of 1084 MSF forms from faculty (40%), senior residents (34%), nurses (22%), and other staff (4%). Variance in ratings was associated primarily with rater (32%) and learner (22%). The milestone factor structure fit data better than simpler structures. In domains except professionalism, ratings by nurses were significantly lower than those by faculty and ratings by other staff were significantly higher. Ratings were higher when the rater observed the learner for longer periods and had a positive global opinion of the learner. Ratings of interns and subinterns did not differ, except for ratings by senior residents. MSF-based scales correlated with summative milestone scores.

Conclusion: We obtain moderately reliable MSF ratings of interns and subinterns in the inpatient context to inform some milestone assignments.