Improving Outcomes in Patients With Sepsis.

Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function.

Evaluation of apoptogenic adenovirus type 5 oncolytic vectors in a Syrian hamster head and neck cancer model.

Human adenovirus (HAdV) vectors are intensely investigated for virotherapy of a wide variety of human cancers. Here, we have evaluated the effect of two apoptogenic HAdV5 vectors in an immunocompetent Syrian hamster animal model of head and neck cancer. We established two cell lines of hamster cheek pouch squamous cell carcinomas, induced by treatment with 9,10-dimethyl-1,2-benzanthracene. These cell lines, when infected with HAdV5 mutants lp11w and lp11w/Δ55 K (which are defective in the expression of either E1B-19 K alone or both E1B-19 K and E1B-55 K proteins) exhibited enhanced apoptotic and cytotoxic responses. The cheek pouch tumor cells transplanted either subcutaneously at the flanks or in the cheek pouches of hamsters readily formed tumors. Intratumoral administration of HAdV5-E1B mutants efficiently suppressed the growth of tumors at both sites. Histological examination of orthotopic tumors revealed reduced vascularity and the expression of the viral fiber antigen in virus-administered cheek pouch tumors. These tumors also exhibited increased caspase-3 levels, suggesting that virus-induced apoptosis may contribute to tumor growth suppression. Our results suggest that the apoptogenic HAdV5 vectors may have utility for the treatment of human head and neck cancers.

Improved physician consult response times in an academic Emergency Department after implementation of an institutional guideline.

BACKGROUND: Physician consultation in the Emergency Department (ED) can account for a significant portion of ED length of stay, which can lead to poor clinical outcomes. OBJECTIVE: The purpose of this study was to determine whether an institutional guideline could lead to a reduction in time between consult request and admission decision. This guideline codified a 90-min expected time interval to arrive and complete an admission disposition where the consulting and admitting service were the same in an academic ED with weekly audits and reports to departmental chairs and hospital administrators. METHODS: This was a study of consultation times of patients who presented to an academic ED 6 months before the adoption of an institutional guideline and 6 months after the adoption of the guideline. Data measurement in both periods included the length of time from ED consult order to admission disposition, time of ED discharge, number of ED consultations (single and multiple), ED admissions, and the hospital discharge time of admitted patients. RESULTS: Physician consult response time decreased from 121 min to 100 min (p < 0.0001), and patients left the ED 18 min earlier (p = 0.0221) after implementation of the consultation guideline despite more ED visits, consultations, and admissions in the post-implementation time period. Patients were discharged from the inpatient setting 50 min later (p < 0.0001) after implementation of the guideline. CONCLUSION: An institutional guideline codifying timely ED consultations led to a significant reduction in the time from ED consultation to admission disposition while also allowing patients to leave the ED earlier in a high-occupancy academic medical center. However, the discharge time of admitted hospital patients was later after implementation of the guideline.

Reduction of central venous catheter associated blood stream infections following implementation of a resident oversight and credentialing policy.

BACKGROUND: This study assesses the impact that a resident oversight and credentialing policy for central venous catheter (CVC) placement had on institution-wide central line associated bloodstream infections (CLABSI). We therefore investigated the rate of CLABSI per 1,000 line days during the 12 months before and after implementation of the policy. METHODS: This is a retrospective analysis of prospectively collected data at an academic medical center with four adult ICUs and a pediatric ICU. All patients undergoing non-tunneled CVC placement were included in the study. Data was collected on CLABSI, line days, and serious adverse events in the year prior to and following policy implementation on 9/01/08. RESULTS: A total of 813 supervised central lines were self-reported by residents in four departments. Statistical analysis was performed using paired Wilcoxon signed rank tests. There were reductions in median CLABSI rate (3.52 vs. 2.26; p = 0.015), number of CLBSI per month (16.0 to 10.0; p = 0.012), and line days (4495 vs. 4193; p = 0.019). No serious adverse events reported to the Pennsylvania Patient Safety Authority. CONCLUSIONS: Implementation of a new CVC resident oversight and credentialing policy has been significantly associated with an institution-wide reduction in the rate of CLABSI per 1,000 central line days and total central line days. No serious adverse events were reported. Similar resident oversight policies may benefit other teaching institutions, and support concurrent organizational efforts to reduce hospital acquired infections.

A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus.

Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola, the etiological agent of smallpox. In humans, MPXV causes a disease similar to smallpox and is considered to be an emerging infectious disease. Moreover, the use of MPXV for bioterroristic/biowarfare activities is of significant concern. Available small animal models of human monkeypox have been restricted to mammals with poorly defined biologies that also have limited reagent availability. We have established a murine MPXV model utilizing the STAT1-deficient C57BL/6 mouse. Here we report that a relatively low-dose intranasal (IN) infection induces 100% mortality in the stat1(-)(/)(-) model by day 10 postinfection with high infectious titers in the livers, spleens, and lungs of moribund animals. Vaccination with modified vaccinia virus Ankara (MVA) followed by a booster vaccination is sufficient to protect against an intranasal MPXV challenge and induces an immune response more robust than that of a single vaccination. Furthermore, antiviral treatment with CMX001 (HDP-cidofovir) and ST-246 protects when administered as a regimen initiated on the day of infection. Thus, the stat1(-)(/)(-) model provides a lethal murine platform for evaluating therapeutics and for investigating the immunological and pathological responses to MPXV infection.

MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice.

Breast cancer is the leading cause of cancer death among women. We have shown previously an antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of breast cancer growth and metastasis in an immunocompetent mouse model. For this, we have used a mouse breast cancer cell line (EO771) and syngeneic C57BL/6 mice. EO771 cells were implanted into the mammary fat pad of C57BL/6 mice. Replication-deficient recombinant adenovirus expressing MBP-1 was administered intratumorally to determine gene therapeutic potential. The results showed a significant regression of primary and distant (lung) tumor growth. Animals exhibited prolonged survival on treatment with MBP-1 compared with the control group (dl312). Subsequent studies suggested that MBP-1 inhibits matrix metalloproteinase expression in human breast cancer cells. Cells transduced with MBP-1 displayed inhibition of migration in a wound-healing assay. The conditioned medium from MBP-1-transduced cells blocked in vitro tube formation assay and inhibited expression of several angiogenic molecules. Taken together, our study shows that MBP-1 acts as a double-edged sword by inhibiting primary and metastatic tumor growth and modulating matrix metalloproteinase expression with a therapeutic potential against breast cancer progression.

Use of the i-STAT portable clinical analyzer in mice.

The use of portable chemistry analyzers is an attractive option for obtaining clinical pathology panels in mice, because these analyzers require only small volumes of whole blood. However, in studies with other animals, portable analyzers do not always agree with results obtained using standard laboratory equipment. The authors evaluated the use of the i-STAT handheld portable clinical analyzer compared to the use of standard nonportable laboratory instruments in mice. As shown with other species, the i-STAT results did not always agree with standard laboratory instruments; however, the i-STAT does show reliability for certain chemistry assays.