Improving Blood Product Transfusion Premedication Plan Documentation: A Single-institution Quality Improvement Effort.

Introduction: Premedication with acetaminophen and/or diphenhydramine to prevent febrile nonhemolytic transfusion reactions and minor allergic transfusion reactions is a common practice based on historical recommendations. However, recent small randomized-controlled trials showed no benefit of premedication. This inconsistency leads to practice variability, which results in the inefficiency of our institution's blood product ordering process. This project aimed to improve the number of transfusion encounters with premedication plan documentation from a baseline of 19% to 80% in 12 months. Methods: A multidisciplinary quality improvement (QI) team used QI tools to design interventions to improve the efficiency of the ordering process for blood products. Measures were tracked monthly and analyzed using statistical process control. Results: From September 2018 to January 2021, 5,351 blood product transfusion visits were scheduled. At baseline, 34% of patients received premedication, and 19% had premedication plans documented. Interventions included a passive computerized provider order entry alert, clinical care pathway development, and clinician education. Postimplementation, the average number of encounters with a premedication plan increased from 19% to 87%, whereas encounters receiving premedication decreased from 34% to 25%. There was no change in the average number of transfusion reactions (1.8 per 100 transfusions). Conclusions: Using QI methods, our team successfully standardized the blood product premedication plan documentation despite unclear best practices regarding blood product transfusion premedication. The team added premedication plan documentation training to new employee orientation for sustainability.

Reducing Time to Discharge after Chemotherapy by Standardizing Workflow and Providing Outpatient Intravenous Hydration.

INTRODUCTION: Patients receiving cyclophosphamide or ifosfamide chemotherapy require intravenous fluid hydration to prevent hemorrhagic cystitis. In selected patients without medical contraindications (ie, excess nausea/vomiting), this hydration may be completed after discharge. We aimed to reduce the time to discharge after completing mesna in patients receiving cyclophosphamide or ifosfamide therapy on an inpatient chemotherapy service. METHODS: The quality improvement team performed a medical record review to capture the time to discharge after mesna therapy and the readmission rate and used quality improvement methods to redesign discharge workflow and increase patient involvement with the discharge process. RESULTS: From August 2017 through July 2018, there were 160 admission encounters (73 patients) for cyclophosphamide or ifosfamide on a dedicated chemotherapy service. Of those encounters, 89 (55.6%) were appropriate for outpatient hydration; 48 (53.9%) of these encounters involved a patient who elected to receive outpatient hydration. Although the median time to discharge for the whole cohort did not change, in encounters where patients chose intravenous outpatient hydration, the median time to discharge was reduced from 2.82 to 0.66 hours (76.6% reduction) after implementing the new discharge workflow. No patients experienced readmission within 48 hours. CONCLUSIONS: Discharge workflow redesign and standardization reduced the time to discharge after chemotherapy in patients who chose outpatient hydration. Outpatient intravenous hydration after cyclophosphamide or ifosfamide appears safe and feasible in selected patient populations.

Stakeholder perceptions and scientific evidence linking wildfire mitigation treatments to societal outcomes.

A number of watershed partnerships have emerged in the western US to address the impacts of wildfire through investing in wildfire mitigation activities. To motivate collective action and design effective risk mitigation programs, these stakeholders draw on evidence linking wildfire mitigation to outcomes of interest. To advance knowledge in this area, we 1) assessed the strength of existing scientific evidence linking wildfire mitigation treatments with societal outcomes and 2) measured the importance of this evidence to watershed partnerships in the western US. To address objective one, we created a systematic evidence map to identify the most common wildfire mitigation treatment and societal outcome relationships reported. From the more than 100 studies examined, we found that the most commonly studied linkages were related to the impacts of thinning on infrastructure and timber. To answer objective two, we surveyed 38 professionals affiliated with organizations involved in eight watershed partnerships in the western US. We asked about the relative importance and strength of evidence linking wildfire treatments to societal outcomes for their watershed partnership, and used this information to create an importance-strength analysis and gap analysis. We found that most linkages were considered important to these organizations, and that the biggest gap identified was for evidence linking mulching to water quality or quantity outcomes. Forest and wildfire specialists perceived a larger need for additional evidence generation than other professional groups. Jointly, the results from this study point to areas of evidence generation important for watershed partnerships and other organizations involved in wildfire mitigation, and suggest a need to more thoroughly disseminate information about existing evidence to this new group of stakeholders investing in wildfire risk mitigation.

Assessing public support for restrictions on transport of invasive wild pigs (Sus scrofa) in the United States.

Wild pigs (Sus scrofa) are a non-native invasive species in the United States that cause significant economic loss, transmit disease, and inflict damage upon natural resources, agriculture, livestock, and property. Geographic distribution of wild pigs in the United States has nearly tripled since 1982, with anthropogenic influences playing a significant role in the expansion. In this regard, there is speculation that a driver of the expansion may be human-mediated movement of wild pigs to new areas for the purpose of sport hunting. In response, states have implemented a variety of wild pig control policies, including legal restrictions on their transport. The success of such policies depends, in part, on their level of public support, which in turn may be influenced by individuals' attitudes concerning wild pigs, their interest in maintaining wild pig populations (e.g., for sport hunting), and their knowledge and awareness of the threats wild pigs pose. Multiple regression was used to analyze data collected from a nationwide survey concerning attitudes toward wild pigs and policies that restrict their transport. Results indicate that a majority of individuals in the United States have negative attitudes toward wild pigs and support policies that restrict their transport and penalize transgressors. Consistent with other invasive species research, findings suggest that as knowledge and awareness of wild pigs increase, so too does support for policies restricting and penalizing transport of wild pigs. Contrary to previous studies, this research also finds that hunters are more likely to support restrictions on wild pig transport than are non-hunters. Overall, these findings suggest that legal restrictions on the transport of wild pigs, even in states with large hunter populations, enjoy broad public support and may help to curb the expansion of wild pig populations.

A Multidisciplinary Self-Directed Learning Module Improves Knowledge of a Quality Improvement Instrument: The HEART Pathway.

We created and tested an educational intervention to support implementation of an institution wide QI project (the HEART Pathway) designed to improve care for patients with acute chest pain. Although online learning modules have been shown effective in imparting knowledge regarding QI projects, it is unknown whether these modules are effective across specialties and healthcare professions. Participants, including nurses, advanced practice clinicians, house staff and attending physicians (N = 486), were enrolled into an online, self-directed learning course exploring the key concepts of the HEART Pathway. The module was completed by 97% of enrollees (469/486) and 90% passed on the first attempt (422/469). Out of 469 learners, 323 completed the pretest, learning module and posttest in the correct order. Mean test scores across learners improved significantly from 74% to 89% from the pretest to the posttest. Following the intervention, the HEART Pathway was used for 88% of patients presenting to our institution with acute chest pain. Our data demonstrate that this online, self-directed learning module can improve knowledge of the HEART Pathway across specialties-paving the way for more efficient and informed care for acute chest pain patients.

Cost analysis of the History, ECG, Age, Risk factors, and initial Troponin (HEART) Pathway randomized control trial.

INTRODUCTION: The HEART Pathway is a diagnostic protocol designed to identify low-risk patients presenting to the emergency department with chest pain that are safe for early discharge. This protocol has been shown to significantly decrease health care resource utilization compared with usual care. However, the impact of the HEART Pathway on the cost of care has yet to be reported. METHODS AND RESULTS: We performed a cost analysis of patients enrolled in the HEART Pathway trial, which randomized participants to either usual care or the HEART Pathway protocol. For low-risk patients, the HEART Pathway recommended early discharge from the emergency department without further testing. We compared index visit cost, cost at 30 days, and cardiac-related health care cost at 30 days between the 2 treatment arms. Costs for each patient included facility and professional costs. Cost at 30 days included total inpatient and outpatient costs, including the index encounter, regardless of etiology. Cardiac-related health care cost at 30 days included the index encounter and costs adjudicated to be cardiac-related within that period. Two hundred seventy of the 282 patients enrolled in the trial had cost data available for analysis. There was a significant reduction in cost for the HEART Pathway group at 30 days (median cost savings of $216 per individual), which was most evident in low-risk (Thrombolysis In Myocardial Infarction score of 0-1) patients (median savings of $253 per patient) and driven primarily by lower cardiac diagnostic costs in the HEART Pathway group. CONCLUSIONS: Using the HEART Pathway as a decision aid for patients with undifferentiated chest pain resulted in significant cost savings.

Social Media in Professional Medicine: New Resident Perceptions and Practices.

BACKGROUND: For younger generations, unconstrained online social activity is the norm. Little data are available about perceptions among young medical practitioners who enter the professional clinical arena, while the impact of existing social media policy on these perceptions is unclear. OBJECTIVE: The objective of this study was to investigate the existing perceptions about social media and professionalism among new physicians entering in professional clinical practice; and to determine the effects of formal social media instruction and policy on young professionals' ability to navigate case-based scenarios about online behavior in the context of professional medicine. METHODS: This was a prospective observational study involving the new resident physicians at a large academic medical center. Medical residents from 9 specialties were invited to participate and answer an anonymous questionnaire about social media in clinical medicine. Data were analyzed using SAS 9.4 (Cary, NC), chi-square or Fisher's exact test was used as appropriate, and the correct responses were compared between different groups using the Kruskal-Wallis analysis of variance. RESULTS: Familiarity with current institutional policy was associated with an average of 2.2 more correct responses (P=.01). Instruction on social media use during medical school was related to correct responses for 2 additional questions (P=.03). On dividing the groups into no policy exposure, single policy exposure, or both exposures, the mean differences were found to be statistically significant (3.5, 7.5, and 9.4, respectively) (P=.03). CONCLUSIONS: In this study, a number of young physicians demonstrated a casual approach to social media activity in the context of professional medical practice. Several areas of potential educational opportunity and focus were identified: (1) online privacy, (2) maintaining digital professionalism, (3) safeguarding the protected health information of patients, and (4) the impact of existing social media policies. Prior social media instruction and/or familiarity with a social media policy are associated with an improved performance on case-based questions regarding online professionalism. This suggests a correlation between an instruction about online professionalism and more cautious online behavior. Improving the content and delivery of social media policy may assist in preserving institutional priorities, protecting patient information, and safeguarding young professionals from online misadventure.

Facilitating a School-Based Prevention of Commercial Sexual Exploitation of Children.

The challenges of developing and researching a school-based prevention program using the participatory culture-specific intervention model are described here. We outline the problem of commercial sexual exploitation of children that motivated our project and the characteristics of students most at risk (African American girls in middle school). We provide an analysis of the factors that can facilitate creation and implementation of similar prevention programs in schools. These factors include establishing partnerships with community resources, including school insiders, and establishing trust, especially with students placed at risk.

Effects of load on good morning kinematics and EMG activity.

Many strength and conditioning coaches utilize the good morning (GM) to strengthen the hamstrings and spinal erectors. However, little research exists on its electromyography (EMG) activity and kinematics, and how these variables change as a function of load. The purpose of this investigation was to examine how estimated hamstring length, integrated EMG (IEMG) activity of the hamstrings and spinal erectors, and kinematics of the lumbar spine, hip, knee, and ankle are affected by changes in load. Fifteen trained male participants (age = 24.6 ± 5.3 years; body mass = 84.7 ± 11.3 kg; height = 180.9 ± 6.8 cm) were recruited for this study. Participants performed five sets of the GM, utilizing 50, 60, 70, 80, and 90% of one-repetition maximum (1RM) in a randomized fashion. IEMG activity of hamstrings and spinal erectors tended to increase with load. Knee flexion increased with load on all trials. Estimated hamstring length decreased with load. However, lumbar flexion, hip flexion, and plantar flexion experienced no remarkable changes between trials. These data provide insight as to how changing the load of the GM affects EMG activity, kinematic variables, and estimated hamstring length. Implications for hamstring injury prevention are discussed. More research is needed for further insight as to how load affects EMG activity and kinematics of other exercises.

Sexualized and dangerous relationships: listening to the voices of low-income african american girls placed at risk for sexual exploitation.

INTRODUCTION: Youth from low-income, urban backgrounds face significant challenges to maintaining a positive developmental trajectory. Dangerous neighborhoods and stressed relationships are common in these settings and threaten adaptation by weakening the natural assets that undergird resilience. African American girls in these contexts face specific, multiple risks, including gender stereotyping, violence, and sexual exploitation. The commercial sexual exploitation of children (CSEC) is a multibillion-dollar industry victimizing over 1 million children around the globe. The typical victim in 1 city in the southeastern United States is an African American girl 12-14 years old. There has been little research investigating the characteristics of girls placed at risk for CSEC and even less research on the personal perspectives of these girls. METHODS: Over 3 school terms we provided preventive intervention groups for 36 African American middle school girls who were placed at risk because they lived in neighborhoods with high rates of interpersonal violence and CSEC. Two group leaders and a process recorder took detailed notes on each group session. Our focus on group conversations over a period of weeks increased the probability of recording spontaneous, open comments by the children and is a promising method with this population. The data were analyzed qualitatively and resulted in an account of the girls' own views of the environmental challenges and personal experiences that may influence their development. RESULTS: The girls' language during the group sessions contained 4 themes: difficulty forming trusting relationships, frequent peer aggression, familiarity with adult prostitution, and sexuality as a commodity. CONCLUSION: Our research shows how girls placed at risk for CSEC view their own lives. These children described violence and sexual exploitation and cited limited supports to protect them from these risks. Understanding the perspectives of these girls should generate future research and intervention strategies to support their coping and resilience.

Stress CMR reduces revascularization, hospital readmission, and recurrent cardiac testing in intermediate-risk patients with acute chest pain.

OBJECTIVES: The aim of this study was to determine the effect of stress cardiac magnetic resonance (CMR) imaging in an observation unit (OU) on revascularization, hospital readmission, and recurrent cardiac testing in intermediate-risk patients with possible acute coronary syndromes (ACS). BACKGROUND: Intermediate-risk patients commonly undergo hospital admission with high rates of coronary revascularization. It is unknown whether OU-based care with CMR is a more efficient alternative. METHODS: A total of 105 intermediate-risk participants with symptoms of ACS but without definite ACS on the basis of the first electrocardiogram and troponin were randomized to usual care provided by cardiologists and internists (n = 53) or to OU care with stress CMR (n = 52). The primary composite endpoint of coronary artery revascularization, hospital readmission, and recurrent cardiac testing at 90 days was determined. The secondary endpoint was length of stay from randomization to index visit discharge; safety was measured as ACS after discharge. RESULTS: The median age of participants was 56 years (range 35 to 91 years), 54% were men, and 20% had pre-existing coronary disease. Index hospital admission was avoided in 85% of the OU CMR participants. The primary outcome occurred in 20 usual care participants (38%) versus 7 OU CMR participants (13%) (hazard ratio: 3.4; 95% confidence interval: 1.4 to 8.0, p = 0.006). The OU CMR group experienced significant reductions in all components: revascularizations (15% vs. 2%, p = 0.03), hospital readmissions (23% vs. 8%, p = 0.03), and recurrent cardiac testing (17% vs. 4%, p = 0.03). Median length of stay was 26 h (interquartile range: 23 to 45 h) in the usual care group and 21 h (interquartile range: 15 to 25 h) in the OU CMR group (p < 0.001). ACS after discharge occurred in 3 usual care participants (6%) and no OU CMR participants. CONCLUSIONS: In this single-center trial, management of intermediate-risk patients with possible ACS in an OU with stress CMR reduced coronary artery revascularization, hospital readmissions, and recurrent cardiac testing, without an increase in post-discharge ACS at 90 days. (Randomized Investigation of Chest Pain Diagnostic Strategies; NCT01035047).

Provider-directed imaging stress testing reduces health care expenditures in lower-risk chest pain patients presenting to the emergency department.

BACKGROUND: Among intermediate- to high-risk patients with chest pain, we have shown that a cardiac magnetic resonance (CMR) stress test strategy implemented in an observation unit (OU) reduces 1-year health care costs compared with inpatient care. In this study, we compare 2 OU strategies to determine among lower-risk patients if a mandatory CMR stress test strategy was more effective than a physicians' ability to select a stress test modality. METHODS AND RESULTS: On emergency department arrival and referral to the OU for management of low- to intermediate-risk chest pain, 120 individuals were randomly assigned to receive (1) a CMR stress imaging test (n=60) or (2) a provider-selected stress test (n=60: stress echo [62%], CMR [32%], cardiac catheterization [3%], nuclear [2%], and coronary CT [2%]). No differences were detected in length of stay (median CMR=24.2 hours versus 23.8 hours, P=0.75), catheterization without revascularization (CMR=0% versus 3%), appropriateness of admission decisions (CMR 87% versus 93%, P=0.36), or 30-day acute coronary syndrome (both 3%). Median cost was higher among those randomly assigned to the CMR-mandated group ($2005 versus $1686, P<0.001). CONCLUSIONS: In patients with lower-risk chest pain receiving emergency department-directed OU care, the ability of a physician to select a cardiac stress imaging modality (including echocardiography, CMR, or radionuclide testing) was more cost-effective than a pathway that mandates a CMR stress test. Contrary to prior observations in individuals with intermediate- to high-risk chest pain, in those with lower-risk chest pain, these results highlight the importance of physician-related choices during acute coronary syndrome diagnostic protocols. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00869245.

Stress CMR imaging observation unit in the emergency department reduces 1-year medical care costs in patients with acute chest pain: a randomized study for comparison with inpatient care.

OBJECTIVES: This study sought to compare the direct cost of medical care and clinical events during the first year after patients with intermediate risk acute chest pain were randomized to stress cardiac magnetic resonance (CMR) observation unit (OU) testing versus inpatient care. BACKGROUND: In a recent study, randomization to OU-CMR reduced median index hospitalization cost compared with the cost of inpatient care in patients presenting to the emergency department with intermediate risk acute chest pain. METHODS: Emergency department patients with intermediate risk chest pain were randomized to OU-CMR (OU care, cardiac markers, stress CMR) or inpatient care (admission, care per admitting provider). This analysis reports the direct cost of cardiac-related care and clinical outcomes (myocardial infarction, revascularization, cardiovascular death) during the first year of follow-up subsequent to discharge. Consistent with health economics literature, provider cost was calculated from work-related relative value units using the Medicare conversion factor; facility charges were converted to cost using departmental-specific cost-to-charge ratios. Linear models were used to compare cost accumulation among study groups. RESULTS: We included 109 randomized subjects in this analysis (52 OU-CMR, 57 inpatient care). The median age was 56 years; baseline characteristics were similar in both groups. At 1 year, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p = 0.72) with 1 patient in each group experiencing a cardiac event after discharge. First-year cardiac-related costs were significantly lower for participants randomized to OU-CMR than for participants receiving inpatient care (geometric mean = $3,101 vs. $4,742 including the index visit [p = 0.004] and $29 vs. $152 following discharge [p = 0.012]). During the year following randomization, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p = 0.72). CONCLUSIONS: An OU-CMR strategy reduces cardiac-related costs of medical care during the index visit and over the first year subsequent to discharge, without an observed increase in major cardiac events. (Cost Comparison of Cardiac Magnetic Resonance Imaging [MRI] Use in Emergency Department [ED] Patients With Chest Pain; NCT00678639).

Stress cardiac magnetic resonance imaging with observation unit care reduces cost for patients with emergent chest pain: a randomized trial.

STUDY OBJECTIVE: We determine whether imaging with cardiac magnetic resonance imaging (MRI) in an observation unit would reduce medical costs among patients with emergent non-low-risk chest pain who otherwise would be managed with an inpatient care strategy. METHODS: Emergency department patients (n=110) at intermediate or high probability for acute coronary syndrome without electrocardiographic or biomarker evidence of a myocardial infarction provided consent and were randomized to stress cardiac MRI in an observation unit versus standard inpatient care. The primary outcome was direct hospital cost calculated as the sum of hospital and provider costs. Estimated median cost differences (Hodges-Lehmann) and distribution-free 95% confidence intervals (Moses) were used to compare groups. RESULTS: There were 110 participants with 53 randomized to cardiac MRI and 57 to inpatient care; 8 of 110 (7%) experienced acute coronary syndrome. In the MRI pathway, 49 of 53 underwent stress cardiac MRI, 11 of 53 were admitted, 1 left against medical advice, 41 were discharged, and 2 had acute coronary syndrome. In the inpatient care pathway, 39 of 57 patients initially received stress testing, 54 of 57 were admitted, 3 left against medical advice, and 6 had acute coronary syndrome. At 30 days, no subjects in either group experienced acute coronary syndrome after discharge. The cardiac MRI group had a reduced median hospitalization cost (Hodges-Lehmann estimate $588; 95% confidence interval $336 to $811); 79% were managed without hospital admission. CONCLUSION: Compared with inpatient care, an observation unit strategy involving stress cardiac MRI reduced incident cost without any cases of missed acute coronary syndrome in patients with emergent chest pain.

Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis.

T helper (Th) 17 cells have recently been implicated in psoriasis pathogenesis, but mechanisms of how these cells traffic into inflamed skin are unknown. By immunostaining for interleukin (IL)-17A and IL-22, we show numerous cells present in psoriasis lesions that produce these cytokines. We next found that Th17 cytokines (IL-17A, IL-22, and tumor necrosis factor (TNF)-alpha) markedly increased the expression of CC chemokine ligand (CCL) 20, a CC chemokine receptor (CCR)6 ligand, in human keratinocyte monolayer and raft cultures in a dose- and time-dependent manner. Lastly, we showed in mice that subcutaneous injection with recombinant IL-17A, IL-22, or TNF-alpha led to the upregulation of both CCL20 and CCR6 expression in skin as well as cutaneous T-cell infiltration. Taken together, these data show that Th17 cytokines stimulate CCL20 production in vitro and in vivo, and thus provide a potential explanation of how CCR6-positive Th17 cells maintain their continual presence in psoriasis through a positive chemotactic feedback loop.

Efalizumab therapy for atopic dermatitis causes marked increases in circulating effector memory CD4+ T cells that express cutaneous lymphocyte antigen.

Efalizumab is an mAb directed against CD11a, a molecule involved in T-cell activation and extravasation from blood into tissue. Ten patients with severe atopic dermatitis were treated with efalizumab for 84 days, and peripheral blood mononuclear cells were analyzed for expression of activation and adhesion markers. Efalizumab treatment led to decreases in CD11a mean fluorescence intensity (MFI) on naive, central memory, and effector memory CD4+ and CD8+ T cell subsets. MFI for CD18 was decreased in both CD4+ and CD8+ T cells. Percentages of cells positive for cutaneous lymphocyte antigen (CLA) were increased fourfold in all CD4+ and CD8+ T cell subsets. Increases in the percentages of CD4+ and CD8+ T cells expressing beta7 and CD49d were also observed. No significant changes were observed in the percentages of CD4+ and CD8+ T cells that produced either IFN-gamma or IL-4. In summary, efalizumab treatment resulted in (i) decreases in CD11a and CD18 expression in all circulating T-cell subsets and (ii) increases in the percentages of blood T cells expressing tissue homing markers (CLA, beta7, CD49d). These data suggest that blockade of T-cell extravasation into tissue is the major pathway by which efalizumab leads to improvement in cutaneous inflammation.

Efalizumab for severe atopic dermatitis: a pilot study in adults.

BACKGROUND: Severe atopic dermatitis (AD) often cannot be adequately controlled with topical agents. The continuous use of current systemic therapies for AD is limited by end-organ toxicities. A safe and effective systemic therapy for patients with recalcitrant AD is greatly needed. OBJECTIVE: To evaluate the potential safety and efficacy of efalizumab, an inhibitor of T cell activation and migration, in adults with severe AD. METHODS: An investigator-initiated, prospective, open-label, pilot study was conducted involving ten subjects with severe AD. Subjects received an initial conditioning subcutaneous dose of efalizumab of 0.7 mg/kg followed by 1.0 mg/kg weekly for another 11 weeks for a total of 12 doses. The primary efficacy outcome was the change in the mean Eczema Area and Severity Index (EASI) score from baseline as measured at week 12. Monitoring of adverse events continued for 8 weeks after discontinuation of therapy. RESULTS: EASI scores improved from a mean baseline score of 37.1 +/- 13.5 to 17.6 +/- 14.5 at week 12 (52.3% improvement; P < .0001). Six out of ten subjects reached at least a 50% improvement in EASI score by week 12. Pruritus levels decreased from 6.9 cm +/- 1.8 cm to 4.9 cm +/- 2.5 cm utilizing a visual analogue score (P < .015). Overall, efalizumab was well tolerated. There were three significant adverse events during the course of this study, including thrombocytopenia, viral gastroenteritis, and a subject with worsening of disease beyond baseline levels after drug discontinuation. LIMITATIONS: It is difficult to apply these findings to larger populations of patients with AD because this study lacked a control group and involved a small number of subjects with very severe disease. Long-term efficacy and safety of efalizumab in this population is not known. CONCLUSIONS: Efalizumab therapy resulted in significant clinical improvements in six of ten subjects with severe AD. Efalizumab may serve as a good alternative to current systemic immunosuppressants used for AD; however, double-blind placebo-controlled studies are needed to test its efficacy and safety.

Tissue heavy metal concentrations of stranded California sea lions (Zalophus californianus) in Southern California.

Concentrations of nine heavy metals (As, Cd, Cu, Fe, Hg, Pb, Mn, Mo and Zn) were determined in the hepatic and renal tissues of 80 stranded California sea lions (Zalophus californianus). Significant age-dependant increases were observed in liver and kidney concentrations of cadmium and mercury, and renal zinc concentrations. Hepatic iron concentrations were significantly higher in females than males. Animals with suspected domoic acid associated pathological findings had significantly higher concentrations of liver and kidney cadmium; and significantly higher liver mercury concentrations when compared to animals classified with infectious disease or traumatic mortality. Significantly higher hepatic burdens of molybdenum and zinc were found in animals that died from infectious diseases. This is the largest study of tissue heavy metal concentrations in California sea lions to date. These data demonstrate how passive monitoring of stranded animals can provide insight into environmental impacts on marine mammals.

Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines.

T helper (Th) 17 cells, a novel T-cell subset, have been implicated in the pathogenesis of psoriasis and other autoimmune inflammatory diseases. Interleukin (IL)-23 stimulates survival and proliferation of Th17 cells, and thus serves as a key master cytokine regulator for these diseases. In psoriasis, IL-23 is overproduced by dendritic cells and keratinocytes, and this cytokine stimulates Th17 cells within dermis to make IL-17A and IL-22. IL-22, in particular, drives keratinocyte hyperproliferation in psoriasis. Future targeting of these key cytokines is likely to lead to dramatic clinical improvement in patients with psoriasis. This review focuses on the numerous recent studies on the roles of IL-23 and Th17 cells in the pathogenesis of psoriasis.

Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes.

Quiescent epidermis anchors to laminin 5 in the basement membrane via integrin alpha6beta4. Wounding elevates expression of laminin 5, generating leading keratinocytes (LKs) that migrate via beta1 integrins. Laminin 5 was evaluated as a regulator of cell signaling, and mRNA and protein expression in LKs. An in vitro wound model was developed based on suspension and re-adhesion of quiescent human keratinocytes (HKs). DNA microarrays identified multiple mRNAs elevated 1.5 hours after suspension and re-adhesion including activation transcription factor 3 (ATF3). In vitro and in vivo, levels of ATF3 protein elevate in nuclei of LKs, but not in nuclei of the following cells, 2 hours after suspension or wounding but decline by 12-18 hours post injury. Significantly, null defects in laminin 5 or integrin beta4 that inhibit anchorage chronically elevate ATF3 in vivo. This suggests that adhesion to laminin 5, but not other ligands, suppresses activation. On suspension, ATF3 and other transcripts in the microarrays are elevated by phosphorylated p38 mitogen-activated protein kinase (P-p38), a stress kinase that regulates mRNA and cell motility. Inhibition of P-p38 with SB203580 prevents phosphorylation of ATF2, a transcription factor for ATF3 in LKs. Re-adhesion to laminin 5 via alpha6beta4 dephosphorylates P-p38 and suppresses ATF3 protein relative to cells in suspension. Thus, wounding of quiescent HKs disrupts laminin 5 adhesion to activate p38, generating mRNA transcripts that define LKs. Adhesion to deposits of laminin 5 via alpha6beta4 suppresses P-p38 and activation mRNAs including ATF3. Defects in laminin 5 and alpha6beta4 sustain P-p38 with probable pathological effects on transcription and migration.