Tankyrase represses autoinflammation through the attenuation of TLR2 signaling.

Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.

Hospital uncompensated care and patient experience: An instrumental variable approach.

OBJECTIVE: Examine the endogenous relationship between uncompensated care and hospital patient experience scores. DATA SOURCES/STUDY SETTING: The Hospital Consumer Assessment of Healthcare Providers and Systems Survey, CMS Healthcare Cost Report Information System, and the US Census Bureau. STUDY DESIGN: The exogenous change in uncompensated care caused by the 2014 Medicaid expansion was exploited to measure the effect of uncompensated care on patient experience scores using a 2SLS regression with instrumental variables approach. DATA COLLECTION/EXTRACTION METHODS: U.S. general, short-term hospitals whose DSH status remained constant and had nonmissing data for 2011-2015, which totaled 969 unique hospitals per year. PRINCIPAL FINDINGS: The effect of uncompensated care on patient experience was in the predicted direction, with three of the 10 measures being statistically significant. A one percentage point increase in uncompensated care costs resulted in a 0.25-0.50 percentage point decrease in select patient experience scores. CONCLUSIONS: Results indicate a weak relationship between uncompensated care and patient experience scores, as a reduction in uncompensated care is related to quality improvement for some hospitals. These findings have implications for hospitals as they navigate changing reimbursement structures and policy makers considering changes to Obama-era health care reforms.

The ACA Medicaid Expansion, Disproportionate Share Hospitals, and Uncompensated Care.

OBJECTIVE: To estimate the effect of the first full year of the ACA Medicaid expansion on hospital provision of uncompensated care, with special attention paid to hospitals that treat a disproportionate share of low-income patients. DATA SOURCES: Data from a balanced panel of short-term, general, nonfederal, Medicare-certified hospitals were obtained from Medicare cost reports from 2011 to 2014. STUDY DESIGN/STUDY SETTING: A series of difference-in-differences analyses were performed using hospitals in nonexpansion states as the control group. The dependent variable is hospital provision of uncompensated care. DATA COLLECTION/EXTRACTION METHODS: The data were downloaded from the National Bureau of Economic Research website. PRINCIPAL FINDINGS: The Medicaid expansion significantly reduced hospital provision of uncompensated care in 2014. In particular, within expansion states, DSH hospitals saw reductions beyond those experienced by non-DSH hospitals. CONCLUSIONS: Evidence from this study indicates that the Medicaid expansion served to widen an already broad gap in provision of uncompensated care between hospitals in expansion and nonexpansion states. In addition, within expansion states, variation in uncompensated care between hospitals that treat a disproportionate share of low-income patients and those that do not was reduced, with the former experiencing significantly larger reductions. Lawmakers considering expanding Medicaid and those deciding appropriate levels of DSH payments should consider these findings.