Immunomodulatory Roles of CTRP3 in Endotoxemia and Metabolic Stress

C1q/TNF-related protein 3 (CTRP3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human and rodent models of obesity, a metabolic state accompanied by chronic low-grade inflammation. Recent studies have demonstrated an anti-inflammatory role for recombinant CTRP3 in attenuating LPS-induced systemic inflammation, and its deficiency markedly exacerbates inflammation in a mouse model of rheumatoid arthritis. We used genetic mouse models to explore the immunomodulatory function of CTRP3 in response to acute (LPS challenge) and chronic (high-fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP3 deficiency nor its overexpression in transgenic mice had an impact on IL-1β, IL-6, TNF-α, or MIP-2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild-type and CTRP3 transgenic mice fed a high-fat diet or a matched control low-fat diet. On a low-fat diet, CTRP3 transgenic mice had elevated circulating levels of multiple chemokines (CCL11, CXCL9, CXCL10, CCL17, CX3CL1, CCL22 and sCD30). However, when obesity was induced with a high-fat diet, CTRP3 transgenic mice had lower circulating levels of IL-5, TNF-α, sVEGF2, and sVEGFR3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP3 overexpression altered chemokine levels in lean mice, and attenuated systemic inflammation in the setting of obesity and insulin resistance. These results highlight a context-dependent immunomodulatory role for CTRP3

A New Approach to Staging Diabetic Eye Disease: Staging of Diabetic Retinal Neurodegeneration and Diabetic Macular Edema

Biomarkers; Diabetic retinal disease; Neuro-retinal layersBiomarcadores; Enfermedad de la retina diabética; Capas neurorretinianasBiomarcadors; Malaltia de la retina diabètica; Capes neurorretinàriesTopic The goal of this review was to summarize the current level of evidence on biomarkers to quantify diabetic retinal neurodegeneration (DRN) and diabetic macular edema (DME). Clinical relevance With advances in retinal diagnostics, we have more data on patients with diabetes than ever before. However, the staging system for diabetic retinal disease is still based only on color fundus photographs and we do not have clear guidelines on how to incorporate data from the relatively newer modalities into clinical practice. Methods In this review, we use a Delphi process with experts to identify the most promising modalities to identify DRN and DME. These included microperimetry, full-field flash electroretinogram, spectral-domain OCT, adaptive optics, and OCT angiography. We then used a previously published method of determining the evidence level to complete detailed evidence grids for each modality. Results Our results showed that among the modalities evaluated, the level of evidence to quantify DRN and DME was highest for OCT (level 1) and lowest for adaptive optics (level 4). Conclusion For most of the modalities evaluated, prospective studies are needed to elucidate their role in the management and outcomes of diabetic retinal diseases

Development and implementation of a workshop for young adults with diabetes entering college and the workforce

The process of transitioning from pediatric to adult diabetes care for adolescents and young adults is challenging. This transition period may include many life changes, and can be fraught with worsening glycemic control leading to increased risk for diabetes-related hospitalizations and complications. Research has demonstrated that increased support during this period can help maintain engagement in diabetes care. Transition guidelines highlight the importance of preparation and readiness for transition. In this article, we discuss the development, implementation and content of a workshop for patients and parents/caregivers preparing for the transition to college, the workforce and adult diabetes care

Framing the discussion of microorganisms as a facet of social equity in human health

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure

Galaxy Mergers and Dark Matter Halo Mergers in LCDM: Mass, Redshift, and Mass-Ratio Dependence

We employ a high-resolution LCDM N-body simulation to present merger rate predictions for dark matter halos and investigate how common merger-related observables for galaxies--such as close pair counts, starburst counts, and the morphologically disturbed fraction--likely scale with luminosity, stellar mass, merger mass ratio, and redshift from z=0 to z=4. We provide a simple 'universal' fitting formula that describes our derived merger rates for dark matter halos a function of dark halo mass, merger mass ratio, and redshift, and go on to predict galaxy merger rates using number density-matching to associate halos with galaxies. For example, we find that the instantaneous merger rate of m/M>0.3 mass ratio events into typical L > f L* galaxies follows the simple relation dN/dt=0.03(1+f)(1+z)^2.1 Gyr^-1. Despite the rapid increase in merger rate with redshift, only a small fraction of >0.4 L* high-redshift galaxies (~3% at z=2) should have experienced a major merger (m/M >0.3) in the very recent past (t< 100 Myr). This suggests that short-lived, merger-induced bursts of star formation should not contribute significantly to the global star formation rate at early times, in agreement with observational indications. We emphasize that great care must be made in comparisons to observations because the predicted observables depend very sensitively on galaxy luminosity, redshift, overall mass ratio, and uncertain relaxation timescales for merger remnants. We show that the majority of bright galaxies at z=3 should have undergone a major merger (>0.3) in the last 700 Myr and conclude that mergers almost certainly play an important role in delivering baryons and influencing the kinematic properties of Lyman Break Galaxies (LBGs). (abridged)Comment: 11 pages, 4 figures, 2 tables; v2 updated to match published version in ApJ. Includes expanded discussion, and fixes typo in "galaxy stellar mass mergers" fitting paramters. Primary results and conclusions unchange

Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection

ImportanceUrinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020).InterventionsCPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (&lt;10%) of MDRO UTI, coupled with feedback and education.Main outcomes and measuresThe primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods.ResultsAmong 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P &lt; .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively.Conclusions and relevanceCompared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers.Trial registrationClinicalTrials.gov Identifier: NCT03697096

Stewardship Prompts to Improve Antibiotic Selection for Pneumonia

ImportancePneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020.InterventionCPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (&lt;10%) of MDRO pneumonia, coupled with feedback and education.Main outcomes and measuresThe primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies.ResultsAmong 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P &lt; .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups.Conclusions and relevanceEmpiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged.Trial registrationClinicalTrials.gov Identifier: NCT03697070