Tumors evade immune destruction by actively inducing immune tolerance through the recruitment of CD4+CD25+Foxp3+ regulatory T cells (Treg). We have previously described increased prevalence of these cells in pancreatic adenocarcinoma, but it remains unclear what mechanisms are involved in recruiting Treg into the tumor microenvironment. Here, we postulated that chemokines might direct Treg homing to tumor. We show, in both human pancreatic adenocarcinoma and a murine pancreatic tumor model (Pan02), that tumor cells produce increased levels of ligands for the CCR5 chemokine receptor, and, reciprocally, that CD4+ Foxp3+ Treg, compared with CD4+ Foxp3− effector T cells, preferentially express CCR5. When CCR5/CCL5 signaling is disrupted, either by reducing CCL5 production by tumor cells or by systemic administration of a CCR5 inhibitor (TAK-779), Treg migration to tumors is reduced and tumors are smaller than in control mice. Thus, this study demonstrates the importance of Treg in immune evasion by tumors, how blockade of Treg migration may inhibit tumor growth, and, specifically in pancreatic adenocarcinoma, the role of CCR5 in the homing of tumor-associated Treg. Selective targeting of CCR5/CCL5 signaling may represent a novel immunomodulatory strategy for the treatment of cancer.

and the Bright STAR Authorship Group IMPORTANCE Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics.OBJECTIVE To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. DESIGN, SETTING, AND PARTICIPANTS This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. EXPOSURES A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). MAIN OUTCOMES AND MEASURESThe primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics Ն3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock.RESULTS Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. CONCLUSIONS AND RELEVANCE Multidisciplinary diagnostic stewardship interventions canreduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Reimaging is common, but rarely changes management. Limiting reimaging to patients with concerning neurologic findings or mass effect on initial evaluation could reduce imaging by >50%.

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BACKGROUND: High costs of hospitalization may contribute to financial difficulties for some families. OBJECTIVE: To examine the prevalence of financial distress and medical financial burden in families of hospitalized children and identify factors that can predict financial difficulties. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of parents of hospitalized children at six children’s hospitals between October 2017 and November 2018. MAIN OUTCOMES AND MEASURES: The outcomes were high financial distress and medical financial burden. Multivariable logistic regression identified predictors of each outcome. The primary predictor variable was level of chronic disease (complex chronic disease, C-CD; noncomplex chronic disease, NC-CD; no chronic disease, no-CD). RESULTS: Of 644 invited participants, 526 (82%) were enrolled, with 125 (24%) experiencing high financial distress, and 160 (30%) reporting medical financial burden. Of those, 86 (54%) indicated their medical financial burden was caused by costs associated with their hospitalized child. Neither C-CD nor NC-CD were associated with high financial distress. Child-related medical financial burden was associated with both C-CD and NC-CD (adjusted odds ratio [AOR], 4.98; 95% CI, 2.41-10.29; and AOR, 2.57; 95% CI, 1.11-5.93), compared to no-CD. Although household poverty level was associated with both measures, financial difficulties occurred in all family income brackets. CONCLUSION: Financial difficulties are common in families of hospitalized children. Low-income families and those who have children with chronic conditions are at particular risk; however, financial difficulties affect all subsets of the pediatric population. Hospitalization may be a prime opportunity to identify and engage families at risk for financial distress and medical financial burden.