Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became obese and diabetic on a high-fat diet, and obese mice with myeloid-specific loss of Zfp36 [knockout (KO)] demonstrated increased adipose tissue and liver cytokine mRNA expression compared with Control mice. Unexpectedly, in glucose tolerance testing and hyperinsulinemic-euglycemic clamp studies, myeloid Zfp36 KO mice demonstrated improved insulin sensitivity compared with Control mice. Obese KO and Control mice had similar macrophage infiltration of the adipose depots and similar peripheral cytokine levels, but lean and obese KO mice demonstrated increased Kupffer cell (KC; the hepatic macrophage)-expressed Mac2 compared with lean Control mice. Insulin resistance in obese Control mice was associated with enhanced Zfp36 expression in KCs. Compared with Control mice, KO mice demonstrated increased hepatic mRNA expression of a multitude of classical (M1) inflammatory cytokines/chemokines, and this M1-inflammatory hepatic milieu was associated with enhanced nuclear localization of IKKβ and the p65 subunit of NF-κB. Our data confirm the important role of innate immune cells in regulating hepatic insulin sensitivity and lipid metabolism, challenge-prevailing models in which M1 inflammatory responses predict insulin resistance, and indicate that myeloid-expressed Zfp36 modulates the response to insulin in mice.

BackgroundThere is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making.MethodsThe Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document.ResultsRecommendations were developed for “using available data” and “future clinical studies”. The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.ConclusionThe present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design.

PURPOSE: For many patients with cancer, the frequency of surveillance after primary treatment depends on the risk for cancer recurrence or progression. Lack of risk-aligned surveillance means too many unnecessary surveillance procedures for low-risk patients and not enough for high-risk patients. Using bladder cancer as an example, we examined whether practice determinants differ between Department of Veterans Affairs sites where risk-aligned surveillance was more (risk-aligned sites) or less common (need improvement sites). METHODS: We used our prior quantitative data to identify two risk-aligned sites and four need improvement sites. We performed semistructured interviews with 40 Veterans Affairs staff guided by the Tailored Implementation for Chronic Diseases framework that were deductively coded. We integrated quantitative data (risk-aligned site v need improvement site) and qualitative data from interviews, cross-tabulating salient determinants by site type. RESULTS: There were 14 participants from risk-aligned sites and 26 participants from need improvement sites. Irrespective of site type, we found a lack of knowledge on guideline recommendations. Additional salient determinants at need improvement sites were a lack of resources (“the next available without overbooking is probably seven to eight weeks out”) and an absence of routines to incorporate risk-aligned surveillance (“I have my own guidelines that I've been using for 35 years”). CONCLUSION: Knowledge, resources, and lack of routines were salient barriers to risk-aligned bladder cancer surveillance. Implementation strategies addressing knowledge and resources can likely contribute to more risk-aligned surveillance. In addition, reminders for providers to incorporate risk into their surveillance plans may improve their routines.

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steadily increasing. A diagnosis of CKD/ESRD has been associated with adverse surgical outcomes across numerous procedures. However, few studies have quantified the prevalence and perioperative safety risks of patients with CKD/ESRD undergoing urological surgery. The current study assesses the impact of CKD/ ESRD on perioperative outcomes such as length of stay (LOS), 30and 90-day readmission, and mortality at 365 days after major urological surgery in New York State.METHODS: Using the New York Statewide Planning and Research Cooperative System (SPARCS) database, all patients undergoing the 4 most common major urological operations -radical prostatectomy (RP), radical cystectomy (RC), partial nephrectomy (PN), and radical nephrectomy (RN) -were identified from 2009 to 2015. Patients were divided into non-CKD, mild CKD, moderate CKD and severe CKD/ESRD groups based on diagnosis codes.RESULTS: A total of 54,625 cases were identified from 2009-2015. The proportion of patients who had either CKD or ESRD increased across all procedures over the study period. CKD/ESRD (Fig 1 A/B) were independently associated with increased LOS, 30-day, and 90-day readmission in RP and RN. Likewise, renal dysfunction was associated with increased LOS in PN, and increased 90-day readmission in RC. Finally, ESRD was associated with increased mortality at one year for RC, PN and RN (OR 2.52, 8.54, 1.63). Stratification of renal dysfunction revealed that moderate and severe CKD/ESRD were the most significant predictors of worse perioperative outcomes across all procedures.CONCLUSIONS: This study is the largest real-world cohort of patients with CKD/ESRD who underwent major urological operations. Across all 4 procedures, patients with CKD/ESRD had significantly greater risk of adverse outcomes. Despite this, the number of these patients presenting for urological procedures continues to rise. As the global demographics of urological patients continue to evolve, urologists must be aware of the untoward patient safety risks associated with renal dysfunction and equipped to care for this increasingly complex population.