Relevance, quick hits, and vibe: Features of meaningful teaching and learning during trainee consult interactions.

BACKGROUND: Consults are increasingly frequent in inpatient pediatric services. Consult interactions between trainees provide a rich opportunity for teaching and learning. What constitutes meaningful teaching interactions with trainees has not been described. OBJECTIVE: Explore how consulting fellows and residents define "meaningful teaching interactions" associated with inpatient consult interactions. METHODS: Four focus groups were conducted with 21 pediatric trainees (11 subspecialty fellows and 10 residents) at one institution. Transcriptions were analyzed using thematic analysis to inductively create categories and themes. RESULTS: Five factors define meaningful teaching interactions: (1) Relevance; (2) Quick Hits; (3) Vibe; (4) Face-to-face Interactions; and (5) Timing and Busyness. Meaningful content was described as relevant to current or future patient care. Residents valued content that would enable them to explain the reasoning behind recommendations and think through the next steps. Trainees highlighted brief clinical pearls as superior to longer teaching sessions. The "vibe" between resident and fellow was described as a prerequisite to meaningful teaching and included aspects of interest, receptivity, tone, and attitude. Face-to-face interactions were preferred by many trainees, from initial consults to seeing patients or co-rounding. Timing and workload reflected discordant schedules, including time of day and week, but setting a planned time for teaching was beneficial. CONCLUSION: Relevant, bite-sized educational content combined with a good vibe and optimal timing creates a context in which consult fellows can foster meaningful teaching opportunities for residents.

6- and 12-Month Outcomes after 90:10 Enteral Nutrition Induction Therapy in Pediatric Crohn's Disease.

OBJECTIVES: Studies describing longer-term outcomes after EEN induction are limited. We describe clinical outcomes during 90:10 EN induction, and 6- and 12- month outcomes among patients that successfully completed EN induction and then continued either EN or immunomodulator (IM) maintenance therapy. METHODS: All children with CD treated with 90:10 EN induction protocol (90% formula:10% regular diet) at our IBD Center from 2013 to 2018 were retrospectively reviewed. Demographic, clinical, and laboratory data were recorded at baseline, 6, and 12 months (± 3 months at each timepoint). Therapy changes after initiation of EN induction through 12 months were recorded. Among patients that successfully completed 90:10 induction, outcomes between EN and IM maintenance groups were compared. RESULTS: In total, 44/105 (42%) patients completed 8-12 weeks of 90:10 EN induction. Sixty-one patients had incomplete EN induction, with 52% requiring corticosteroids and 25% anti-TNF therapy as alternate induction approaches. Forty-four patients completed EN induction (18 continued EN maintenance and 26 IM maintenance therapy). Twenty-seven of these 44 (61%) remained on initial maintenance therapy at 6 months (10/18 (56%) EN and 17/26 (65%) IM). In total, 16/44 (36%) remained on their initial maintenance therapy at 12 months. By 12 months, 10 patients required anti-TNF and 11 corticosteroids after successful completion of induction. CONCLUSIONS: In this retrospective study of short and longer-term outcomes after 90:10 EN induction, the need for an alternate induction therapy was common, most frequently to anti-TNF or corticosteroid therapy. Future studies are needed to evaluate for predictors of long-term success after EN induction.

Visceral Adipose MicroRNA 223 Is Upregulated in Human and Murine Obesity and Modulates the Inflammatory Phenotype of Macrophages.

Obesity in humans and mice is typified by an activated macrophage phenotype in the visceral adipose tissue (VAT) leading to increased macrophage-mediated inflammation. microRNAs (miRNAs) play an important role in regulating inflammatory pathways in macrophages, and in this study we compared miRNA expression in the VAT of insulin resistant morbidly obese humans to a non-obese cohort with normal glucose tolerance. miR-223-3p was found to be significantly upregulated in the whole omental tissue RNA of 12 human subjects, as were 8 additional miRNAs. We then confirmed that miR-223 upregulation was specific to the stromal vascular cells of human VAT, and found that miR-223 levels were unchanged in adipocytes and circulating monocytes of the non-obese and obese. miR-223 ablation increased basal / unstimulated TLR4 and STAT3 expression and LPS-stimulated TLR4, STAT3, and NOS2 expression in primary macrophages. Conversely, miR-223 mimics decreased TLR4 expression in primary macrophage, at the same time it negatively regulated FBXW7 expression, a well described suppressor of Toll-like receptor 4 (TLR4) signaling. We concluded that the abundance of miR-223 in macrophages significantly modulates macrophage phenotype / activation state and response to stimuli via effects on the TLR4/FBXW7 axis.

Effect of GLP-1 mimetics on blood pressure and relationship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression.

BACKGROUND: Incretin therapies such as glucagon-like peptide 1 (GLP-1) agonists are commonly used for the treatment of type 2 diabetes mellitus. GLP-1 mimetics, besides improving glycemic control, have been shown to influence multiple pathways regulating blood pressure (BP). We investigated the GLP-1 analogs effects on BP from published randomized studies using a meta-analytic approach. METHODS: Thirty-three trials (12,469 patients) that assessed the efficacy of GLP-1 analogs on glycemic control (HbA1C) over 12-56 weeks that met additional criteria, including the availability of standardized sitting BP assessment and weight parameters, were identified. Comparator therapy included oral antiglycemic drugs or placebo. The weighted mean difference (WMD) in systolic BP (SBP) change was calculated using a random-effects model after performing a test for heterogeneity. RESULTS: Forty-one percent of patients were treated with liraglutide (0.3-3mg once daily), whereas 59% were treated with exenatide (5-10 µg twice daily or 2mg weekly). GLP-1 treatment achieved a greater SBP reduction than comparator therapy (WMD = 2.22mm Hg; 95% confidence interval (CI) = -2.97 to -1.47). In the pooled analysis, GLP-1 had beneficial effects on weight loss (WMD = -2.56kg; 95% CI = -3.12 to -2.00), HbA1c reduction (WMD = -0.41%; 95% CI = -0.78 to -0.04) but was associated with a heart rate increase (WMD = 1.30 bpm; 95% CI = 0.26-2.33). In a separate meta-regression analysis, the degree of SBP change was not related to baseline BP, weight loss, or improvement in HbA1C. CONCLUSIONS: This meta-analysis provides evidence that GLP-1 analogs reduce sitting SBP. These findings may support potentially favorable long-term cardiovascular outcomes.

T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance.

A key pathophysiologic role for activated T-cells in mediating adipose inflammation and insulin resistance (IR) has been recently postulated. However, mechanisms underlying their activation are poorly understood. In this study, we demonstrated a previously unrecognized homeostatic role for the costimulatory B7 molecules (CD80 and CD86) in preventing adipose inflammation. Instead of promoting inflammation, which was found in many other disease conditions, B7 costimulation reduced adipose inflammation by maintaining regulatory T-cell (Treg) numbers in adipose tissue. In both humans and mice, expression of CD80 and CD86 was negatively correlated with the degree of IR and adipose tissue macrophage infiltration. Decreased B7 expression in obesity appeared to directly impair Treg proliferation and function that lead to excessive proinflammatory macrophages and the development of IR. CD80/CD86 double knockout (B7 KO) mice had enhanced adipose macrophage inflammation and IR under both high-fat and normal diet conditions, accompanied by reduced Treg development and proliferation. Adoptive transfer of Tregs reversed IR and adipose inflammation in B7 KO mice. Our results suggest an essential role for B7 in maintaining Tregs and adipose homeostasis and may have important implications for therapies that target costimulation in type 2 diabetes.

CXCR3 modulates obesity-induced visceral adipose inflammation and systemic insulin resistance.

OBJECTIVE: Chemokine (C-X-C motif) receptor 3 (CXCR3) is a chemokine receptor involved in the regulation of immune cell trafficking and activation. Increased CXCR3 expression in the visceral adipose of obese humans and mice was observed. A pathophysiologic role for CXCR3 in diet-induced obesity (DIO) was hypothesized. METHODS: Wild-type (WT) C57B/L6J and chemokine receptor 3 knockout (CXCR3(-/-) ) mice were fed a high-fat diet (HFD) for 20 weeks followed by assessment of glucose metabolism and visceral adipose tissue (VAT) inflammation. RESULTS: CXCR3(-/-) mice exhibited lower fasting glucose and improved glucose tolerance compared with WT-HFD mice, despite similar body mass. HFD-induced VAT innate and adaptive immune cell infiltration, including immature myeloid cells (CD11b(+) F4/80(lo) Ly6C(+) ), were markedly ameliorated in CXCR3(-/-) mice. In vitro IBIDI and in vivo migration assays demonstrated no CXCR3-mediated effect on macrophage or monocyte migration, respectively. CXCR3(-/-) macrophages, however, had a blunted response to interferon-γ, a TH 1 cytokine that induces macrophage activation. CONCLUSIONS: A previously unreported role for CXCR3 in the development of HFD-induced insulin resistance (IR) and VAT macrophage infiltration in mice was demonstrated. Our results support pharmaceutical targeting of the CXCR3 receptor as a potential treatment for obesity/IR.

Exercise-mediated changes in high-density lipoprotein: impact on form and function.

The goal of this systematic review was to assess the current understanding of the effects of exercise intervention on high-density lipoprotein (HDL) cholesterol (HDL-C) and changes in HDL function as well as modification of these effects by genomic factors. The reviewed studies demonstrate that exercise has modest effects on HDL-C with limited data suggesting an effect on HDL function. Genetic polymorphisms in proteins associated with HDL metabolism play a role in modifying the HDL-C response to exercise and possibly its function. Exercise as an intervention for patients at risk for cardiovascular events can lead to small improvements in HDL-C and potential changes in HDL function. There is an important modifier effect of genetics in determining these changes.