Faculty Bibliography

Background/Purpose : DLE is a rare, disfiguring disorder in children. Small retrospective studies suggest 20-25% of patients progress to SLE. Progression risk factors are poorly understood, but DLE has been associated with delay in SLE diagnosis and reduced access to care. This multicenter retrospective cohort study aimed to describe baseline characteristics and clinical phenotypes of pediatric DLE patients at diagnosis. Methods : Medical records at eighteen sites were reviewed for pediatric dermatology and rheumatology patients with DLE. For inclusion, patients required clinical and/or histopathologic findings consistent with DLE. Baseline data were collected at the first documented visit including sociodemographic data, ACR/SLICC SLE criteria (i.e. DLE+SLE), date of DLE onset/diagnosis, DLE distribution, family history, comorbidities, and treatment. Outcome variables included ACR (primary outcome) /SLICC SLE criteria. Rates of progression from skin-limited DLE (DLE) to SLE (DLE+SLE) were evaluated. Analysis included descriptive statistics, chi-square and Wilcoxon tests. Results : Out of >1,000 patients reviewed, 441 met inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse (Table 1). A minority presented at baseline with SLE based on ACR and SLICC criteria, respectively (n=165, 37%; n=183, 42%). DLE+SLE patients were older (median 13.7y vs 10.2y) with shorter time from DLE onset to diagnosis (median 2 mo vs 7 mo), compared to DLE patients (p< 0.001). DLE patients presented with low incidence of renal involvement, serositis, seizures or psychosis (p< 0.001, Table 2). DLE+SLE patients had more positive serologies and higher-titer ANAs (p< 0.001, Table 3), although 5% were ANA negative. Among 231 DLE patients with31 follow up visit, median follow-up was 2.7 y (range 0-13.9y) with 747 total subject-years. Progression to SLE occurred in 20% and 25% of patients based on ACR and SLICC criteria, respectively. Conclusion : To date, this is the largest investigation of pediatric DLE. Patients with DLE+SLE were most likely to present in adolescence with abnormal serologies and end-organ disease. Progression of DLE to SLE occurred at rates consistent with previous literature. All patients with DLE require SLE surveillance at diagnosis and regular follow-up, particularly during adolescence. Limitations include the retrospective study design with potential for misclassification, and analysis restricted to the baseline visit. Further analysis of follow up visits will evaluate for baseline risk factors and biomarkers of evolving SLE, as well as timing of progression, identifying DLE patients at highest risk for systemic disease

BACKGROUND:There is a need to directly and accurately conceptualize and measure food insecurity in children as part of surveillance and public health efforts. OBJECTIVE:The aim of this study was to compare parent and child perceptions of child-level food security status via questionnaires within a large, ethnically diverse population. METHODS:Cross-sectional baseline data from a cluster-randomized controlled trial involving primarily low-income, Hispanic third- to fifth-grade students and their parents were used for analysis. The sample consisted of 2408 dyadic (parent and child) pairs. Parents completed the 8-item child-referenced Household Food Security Survey Module and their responses were compared with an adaption of the 5-item Child Food Security Assessment completed by their child. Levels of association between child and parent perceptions within dyads were calculated using Goodman and Kruskal's γ statistic. A mixed-effects binomial logistic regression model was used to model discordance as a function of child, parent, and household sociodemographic characteristics. RESULTS:< 0.001). Children perceived themselves as less food secure than their parents' perception 70.1% of the time. Household receipt of Supplemental Nutrition Assistance Program benefits was associated with greater odds of discordant food security perceptions, whereas female children, older children, and parents not working were characteristics associated with lower odds of discordant perceptions. CONCLUSIONS:Results, in combination with the existing literature, suggest that parent perceptions of child-level food insecurity may underestimate child-level food insecurity experiences. Inaccurate estimations or underestimations of the true prevalence of child-level food insecurity could be detrimental to maternal and child health efforts. This trial was registered at clinicaltrials.gov as NCT02668744.

INTRODUCTION:Implicit bias is a growing area of interest among educators. Educational strategies used to elicit awareness of implicit biases commonly include the Implicit Association Test (IAT). Although the topic of implicit bias is gaining increased attention, emerging critique of the IAT suggests the need to subject its use to greater theoretical and empirical scrutiny. METHODS:The authors employed a meta-narrative synthesis to review existing research on the use of the IAT in health professions education. Four databases were searched using key terms yielding 1151 titles. After title, abstract and full-text screening, 38 articles were chosen for inclusion. Coding and analysis of articles sought a meaningful synthesis of educational approaches relating to the IAT, and the assumptions and theoretical positions that informed these approaches. RESULTS:Distinct, yet complementary, meta-narratives were found in the literature. The dominant perspective utilizes the IAT as a metric of implicit bias to evaluate the success of an educational activity. A contrasting narrative describes the IAT as a tool to promote awareness while triggering discussion and reflection. DISCUSSION:Whether used as a tool to measure bias, raise awareness or trigger reflection, the use of the IAT provokes tension between distinct meta-narratives, posing a challenge to educators. Curriculum designers should consider the premise behind the IAT before using it, and be prepared to address potential reactions from learners such as defensiveness or criticism. Overall, findings suggest that educational approaches regarding implicit bias require critical reflexivity regarding assumptions, values and theoretical positioning related to the IAT.

Background: The prevalence of autoimmune diseases (AIDs) in patients with lung cancer is approximately 14%. However, patients with pre-existing AIDs have been excluded from trials of immune checkpoint inhibitors (ICIs) known to cause immune activation and lead to immune related adverse events (irAEs) limiting the data on safety and efficacy of these agents. Oncologists are therefore wary to use them in this at-risk population.
Method(s): We conducted a single institution IRB-approved retrospective study to evaluate the safety and efficacy of combination and single agent ICI therapy in patients with pre-existing AIDs and concomitant advanced lung cancer that were treated with ICI from 2011 to 2018. Primary endpoints were incidence of irAEs and AID flares. The secondary endpoint was overall survival (OS).
Result(s): We evaluated records from 29 patients with lung cancer of which 17 (59%) had adenocarcinoma, 10 (34%) had squamous cell carcinoma, two (7%) had small cell cancer, and one (3%) had undifferentiated non-small cell lung cancer. AIDs included rheumatic (72%), gastrointestinal (10%), endocrine (10%) and neurologic (7%). 34% of patients experienced an irAE, though only 7% were severe (grade 3-4 colitis and hepatitis). 66% of patients reported no irAEs at all. The most common irAEs were dermatitis (14%) and colitis (10%). 10% of patients had to permanently discontinue ICIs due to an irAE while 17% temporarily held their ICI. 96% of patients with AIDs were either stable or in remission. AID flares were observed in 28% of patients with 24% requiring treatment. None of the AID flares resulted in permanent discontinuation of ICI therapy. 21% of patients were on immunomodulatory therapies at start of ICI treatment. The use of immunomodulatory medications was not associated with an increased incidence of either irAEs or AID flares. Median OS from ICI initiation was 8.5 months and median PFS was 6 months. There was no statistically significant difference for OS or PFS by presence of irAE or presence of immunomodulatory therapy at start of ICI use.
Conclusion(s): In this cohort, patients with pre-existing AIDs and advanced lung cancer reported fewer AID flares (28%) than has been cited in the literature (approximately 50%). IrAEs were seen at an incidence similar to that observed in patients without AIDs. In our cohort, the majority of adverse reactions were manageable and did not require permanent discontinuation of ICI therapy. Furthermore, the presence of irAEs did not detrimentally affect patients' OS or PFS. Based on these findings, we would consider ICI therapy as an option in select patients with pre-existing autoimmunity. Keywords: toxicity, pre-existing autoimmune disease, Immunotherapy
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PURPOSE/OBJECTIVE:To evaluate the relationship of lipocalin-2 to inflammation and cardiac injury with increased aldosterone in HIV. METHODS:A standardized 6-day low sodium diet was used to stimulate RAAS activation, and serum lipocalin-2 and biomarkers of inflammation and cardiac stretch were assessed among persons with and without HIV. RESULTS:Lipocalin-2 (71.3[59.2,99.7] vs. 67.0[51.8,86.3]ng/mL, P=.01) increased with RAAS activation vs. suppression in the HIV group. During RAAS activation, lipocalin-2 was related to biomarkers of inflammation[TNFα(P=.007)], monocyte/macrophage activation[sCD163(P=.005), CcL-2(P=.03)], and markers of cardiac stretch[BNP(P=.0008), NTproBNP(P=.001)] in HIV. CONCLUSION/CONCLUSIONS:Lipocalin-2 may be important in modulating aldosterone-induced inflammation, monocyte activation, and cardiac stretch during RAAS activation in HIV.

A positive association between mental health conditions and poor asthma control has been documented in the World Trade Center-exposed population. Whether factors such as medication adherence mediate this association is unknown. The study population was drawn from adult participants of the World Trade Center Health Registry Cohort who self-reported as asthmatic after the disaster and who were currently prescribed a long-term control medication (LTCM). Multivariable linear regression was used to estimate the associations between mental health condition (PTSD, depression, or anxiety) and continuous adherence and Asthma Control Test (ACT) scores. In the study sample of 1,293, 49% were not adherent to their LTCM and two thirds reported poorly or very poorly controlled asthma. Presence of any mental health condition was associated with a 2-point decline in ACT and half a point decrease in adherence scores. However, in the multivariable model, better adherence was statistically significantly associated with slightly worse control. The total effect of mental health on asthma control was opposite in sign from the product of the paths between mental health and adherence and adherence and asthma control; we therefore found no evidence to support the hypothesis that adherence mediated the negative association between poor mental health and adequate asthma control. More research is needed to understand the complex causal mechanisms that underlie the association between mental and respiratory health.

BACKGROUND:Driven in part by Medicare's Hospital Readmissions Reduction Program, hospitals are focusing on improving the transition from inpatient to outpatient care with particular emphasis on early follow-up with a primary care physician (PCP). OBJECTIVE:To assess whether the implementation of a scheduling assistance program changes rates of PCP follow-up or readmissions. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:An urban tertiary care center PATIENTS: A total of 20,918 adult patients hospitalized and discharged home between September 2008 and October 2015. INTERVENTION/METHODS:A postdischarge appointment service to facilitate early PCP follow-up. MAIN MEASURES/METHODS:Primary outcomes were rates of follow-up visits with a PCP within seven days of discharge and hospital readmission within 30 days of discharge. Our first analysis assessed differences in outcomes among patients with and without the use of the service. In a second analysis, we exploited the fact that the service was not available on weekends and conducted an instrumental variable analysis that used the interaction between the intervention and day of the week of admission. RESULTS:In our multivariable analysis, use of the appointment service was associated with much higher rates of PCP follow-up (+31.9 percentage points, 95% CI: 30.2, 33.6; P < .01) and a decrease in readmission (-3.8 percentage points, 95% CI: -5.2, -2.4; P < .01). In the instrumental variable analysis, use of the service also increased the likelihood of a PCP follow-up visit (33.4 percentage points, 95% CI: 7.9, 58.9; P = .01) but had no significant impact on readmissions (-2.5 percentage points, 95% CI: -22.0, 17.0; P = .80). CONCLUSIONS:The postdischarge appointment service resulted in a substantial increase in timely PCP followup, but its impact on the readmission rate was less clear.

Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes.Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS.Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset (N = 68 total samples). We identified biological pathways that were enriched at each time point in subjects alive and extubated within 28 days after ARDS onset (alive/extubated_Day28) versus those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubated_Day28).Measurements and Main Results: "M1-like" (classically activated) and proinflammatory gene sets such as IL-6/JAK/STAT5 (Janus kinase/signal transducer and activator of transcription 5) signaling were significantly enriched in AMs isolated on Day 1 in alive/extubated_Day28 versus dead/intubated_Day28 subjects. In contrast, by Day 8, many of these same proinflammatory gene sets were enriched in AMs collected from dead/intubated_Day28 compared with alive/extubated_Day28 subjects. Serially sampled alive/extubated_Day28 subjects were characterized by an AM temporal expression pattern of Day 1 enrichment of innate immune programs followed by prompt downregulation on Days 4 and 8. Dead/intubated_Day28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS.Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.