Implementation of an Emergency Department Screening and Care Management Referral Process for Patients With Sickle Cell Disease.

PURPOSE OF STUDY: The purpose of the project was to describe the implementation and evaluation of a care management referral program from emergency departments (EDs) to care management services for patients with sickle cell disease (SCD). PRIMARY PRACTICE SETTING: Patients were referred to Community Care of North Carolina (CCNC), which is a private-public collaboration providing care management services and served as a referral hub for the program. Patients received follow-up from either CCNC or the North Carolina Sickle Cell Syndrome Program. METHODOLOGY AND SAMPLE: A multidisciplinary, multiorganizational group streamlined the referral process for patients with SCD who have ongoing care needs by linking patients from the ED to care management services. The article presents a review of program implementation and evaluation over a 3½-year period. The target population were patients who had a diagnosis of SCD and presented to the ED for treatment. Emergency department staff used a modified version of the Emergency Department Sickle Cell Needs Assessment of Needs and Strengths tool to screen for social behavioral health needs in areas such as emotional, financial, pain management, and resources. All forms were faxed to a central number at CCNC for follow-up care management services. Community Care of North Carolina then linked the patient with the appropriate agency and staff for follow-up. RESULTS: More than 900 referrals were received in 3½ years. Pain was the most common reason for referral. An increase in care management intensity was observed over time. All levels of care management intensity saw an increase in the number of patients. IMPLICATIONS FOR CASE MANAGEMENT: Care management occurred across organizations after careful planning among stakeholders. The interagency cooperation permitted the development of a streamlined process. In particular, the creation of a single point for referral was an important component to allow for population-level monitoring and ease of making referrals. Patients with ongoing care needs were identified and there was an increase in the intensity of outpatient care management services delivered.

Kupffer cell-dependent hepatitis occurs during influenza infection.

Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of "collateral damage" of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.

Quantitative PCR for detection of the OT-1 transgene.

BACKGROUND: Transgenic TCR mice are often used experimentally as a source of T cells of a defined specificity. One of the most widely used transgenic TCR models is the OT-1 transgenic mouse in which the CD8+ T cells express a TCR specific for the SIINFEKL peptide of ovalbumin presented on kb. Although OT-1 CD8+ can be used in a variety of different experimental settings, we principally employ adoptive transfer and peptide-driven expansion of OT-1 cells in order to explore the distribution and fate of these antigen-specific OT-1 T cells. We set out to develop a quantitative PCR assay for OT-1 cells in order to assess the distribution of OT-1 CD8+ T cells in tissues that are either intrinsically difficult to dissociate for flow cytometric analysis or rendered incompatible with flow cytometric analysis through freezing or fixation. RESULTS: We show excellent correlation between flow cytometric assessment of OT-1 cells and OT-1 signal by qPCR assays in cell dilutions as well as in in vivo adoptive transfer experiments. We also demonstrate that qPCR can be performed from archival formalin-fixed paraffin-embedded tissue sections. In addition, the non-quantitative PCR using the OT-1-specific primers without the real-time probe is a valuable tool for OT-1 genotyping, obviating the need for peripheral blood collection and subsequent flow cytometric analysis. CONCLUSION: An OT-1 specific qPCR assay has been developed to quantify adoptively transferred OT-1 cells. OT-1 qPCR to determine cell signal is a valuable adjunct to the standard flow cytometric analysis of OT-1 cell number, particularly in experimental settings where tissue disaggregation is not desirable or in tissues which are not readily disassociated.

TNF-alpha controls intrahepatic T cell apoptosis and peripheral T cell numbers.

At the end of an immune response, activated lymphocyte populations contract, leaving only a small memory population. The deletion of CD8(+) T cells from the periphery is associated with an accumulation of CD8(+) T cells in the liver, resulting in both CD8(+) T cell apoptosis and liver damage. After adoptive transfer and in vivo activation of TCR transgenic CD8(+) T cells, an increased number of activated CD8(+) T cells was observed in the lymph nodes, spleen, and liver of mice treated with anti-TNF-alpha. However, caspase activity was decreased only in CD8(+) T cells in the liver, not in those in the lymphoid organs. These results indicate that TNF-alpha is responsible for inducing apoptosis in the liver and suggest that CD8(+) T cells escaping this mechanism of deletion can recirculate into the periphery.

Biology and significance of T-cell apoptosis in the liver.

The liver has emerged as an organ with distinct immunological properties. In this review, we summarize evidence that shows that the liver can remove apoptotic, or non-apoptotic but activated, CD8+ T cells from the circulation and induce apoptosis in these activated T cells by either active or passive mechanisms. Hepatitis viruses, particularly hepatitis C virus, often establish persistent infection. We review evidence that suggests that these viruses exploit intrahepatic tolerance mechanisms to protect themselves from immune attack.