Chronic kidney disease and value-based care: Lessons from innovation, iteration, and ideation in primary care.

Value-based primary care has reduced health care costs, improved the quality of rendered care, and enhanced the patient experience. Value-based care emphasizes prevention, outreach, follow-up, patient engagement, and comprehensive, whole-person health. Primary care Accountable Care Organizations have leveraged technology-enabled workflows, practice transformation, and cutting-edge data and analytics to achieve success. These efforts are increasingly aided by predictive modeling used in the context of patient identification and prioritization algorithms. Value-based kidney care programs can glean salient takeaways from successful value-based primary care methods and models. The kidney care community is experiencing unprecedented transformation as novel payer programs and financial models burgeon. The authors contend these efforts can be accelerated by the adoption of techniques honed in value-based primary care. To optimize value-based kidney care, though, nephrology thought leaders must transcend the archetype of value-based primary care. To do so, the nephrology community must: (1) impel behavioral change among fee-for-service adherents; (2) harness emerging policy, guidelines, and quality measures; (3) adopt innovative tools, technologies, and therapies. In aggregating lessons from value-based primary care-and leveraging novel methodologies and approaches-the kidney care community will be better equipped to achieve the quadruple aim for kidney care.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA.