Toll-like receptor (TLR) 2 has recently been associated with cellular responses to numerous microbial products, including LPS and bacterial lipoproteins. However, many preparations of LPS contain low concentrations of highly bioactive contaminants described previously as “endotoxin protein,” suggesting that these contaminants could be responsible for the TLR2-mediated signaling observed upon LPS stimulation. To test this hypothesis, commercial preparations of LPS were subjected to a modified phenol re-extraction protocol to eliminate endotoxin protein. While it did not influence the ability to stimulate cells from wild-type mice, repurification eliminated the ability of LPS to activate cells from C3H/HeJ (Lpsd) mice. Additionally, only cell lines transfected with human TLR4, but not human or murine TLR2, acquired responsiveness to both re-extracted LPS and to a protein-free, synthetic preparation of lipid A. These results suggest that neither human nor murine TLR2 plays a role in LPS signaling in the absence of contaminating endotoxin protein.

Clinical and social factors available within hours of hospital presentation and extractable from an EMR predicted mortality and readmission at 30 days. Incorporating complex social factors increased the model's accuracy, suggesting that such factors could enhance risk adjustment models designed to compare hospital readmission rates.

Borrelia burgdorferi lipoproteins activate inflammatory cells through Toll-like receptor 2 (TLR2), suggesting that TLR2 could play a pivotal role in the host response to B. burgdorferi. TLR2 does play a critical role in host defense, as infected TLR2−/− mice harbored up to 100-fold more spirochetes in tissues than did TLR2+/+ littermates. Spirochetes persisted at extremely elevated levels in TLR2-deficient mice for at least 8 wk following infection. Infected TLR2−/− mice developed normal Borrelia-specific Ab responses, as measured by quantity of Borrelia-specific Ig isotypes, the kinetics of class switching to IgG, and the complexity of the Ags recognized. These findings indicate that the failure to control spirochete levels in tissues is not due to an impaired acquired immune response. While macrophages from TLR2−/− mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes. These TLR2-independent responses could play a role during the inflammatory response to B. burgdorferi, as infected TLR2−/− mice developed greater ankle swelling than wild-type littermates. Thus, while TLR2-dependent signaling pathways play a major role in the innate host defense to B. burgdorferi, both inflammatory responses and the development of the acquired humoral response can occur in the absence of TLR2.

Background Administrative data are used in clinical research, but the validity of ICD-9 codes to identify cirrhotic patients has not been well established. Goals Determine the diagnostic accuracy of ICD-9 codes for cirrhosis in clinical practice Study We conducted a retrospective cohort study of patients from a safety-net hospital between 2008-2011. Patients were initially identified using ICD-9 codes for cirrhosis or a resultant complication. The gold-standard diagnosis of cirrhosis was histology and/or imaging based on medical record review. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) for each ICD-9 code were calculated. Diagnostic accuracy was assessed by the c-statistic using receiver operator characteristic curve analysis. Results We identified 2,893 patients with an ICD-9 code for cirrhosis, of whom 50.2% had one ICD-9 code, 20.3% had two different codes, and 29.5% had three or more codes. Cirrhosis was confirmed in 44.0% of patients with one ICD-9 code, 82.6% with two codes, and 95.7% of those with at least three codes. Ascites had a significantly lower PPV for cirrhosis than other ICD-9 codes (p<0.001). The optimal combination of ICD-9 codes to identify cirrhotic patients included all codes except that of ascites, with a c-statistic of 0.71 in our derivation cohort. The sensitivity of this combination was confirmed to be 98% in a validation cohort of 285 patients with known cirrhosis. Conclusions Administrative data can identify patients with cirrhosis with high accuracy, although ascites has a significantly lower positive predictive value than other ICD-9 codes.