Enacted and perceived HIV stigma was examined among substance-using young people living with HIV (YPLH) in Los Angeles, San Francisco, and New York City (N = 147). Almost all YPLH (89%) reported perceived stigma, and 31% reported enacted experiences in the past 3 months; 64% reported experiences during their lifetime. The HIV stigma questions were characterized by factors of avoidance, social rejection, abuse, and shame. In multivariate models, enacted stigma was associated with gay or bisexual identity, symptomatic HIV or AIDS, and bartering sex. Perceived stigma was associated with female gender, symptomatic HIV or AIDS, bartering sex, lower injection drug use, and fewer friends and family knowing serostatus. Gay or bisexual YPLH who were also HIV symptomatic or AIDS diagnosed experienced more HIV stigma than their heterosexual peers.

The non-enteric Gram-negative human pathogens, B. catarrhalis, H. ducreyi, H. influenzae, N. gonorrhoeae and N. meningitidis, do not have repeating O-antigens as part of their principle surface glycolipid, the lipooligosaccharide (LOS). Because they have similar LOS structures, we studied the conservation of LOS oligosaccharide epitopes among these organisms. Twenty-one monoclonal antibodies (mAbs) generated by immunizing mice with H. influenzae, N. gonorrhoeae and N. meningitidis were studied for cross reactivity. Five mAbs generated against non-typable H. influenzae were the only strain-specific antibodies. Ten mAbs reacted to LOS epitope(s) common to a genera or species, and six mAbs bound to epitope(s) on the LOS of strains from different genera. Some cross reactive mAbs bound to LOS bands of similar molecular weights, while others bound to bands of varying molecular weights. mAb 3F11, whose epitope mimics a human blood-group antigen, bound to a 4.8 kDa LOS band in N. gonorrhoeae and H. ducreyi, two pathogens that infect genital epithelium. mAb 3D9, whose epitope consists of 2-keto-3-deoxyoctulosonic acid (KDO), reacted with different LOS bands in N. gonorrhoeae, H. influenzae and some R mutants of S. minnesota. A 14 kb restriction fragment containing lipooligosaccharide synthesis genes responsible for the assembly of the 3D9 epitope in H. influenzae hybridized to all H. influenzae strains tested but did not hybridize to gonococcal and S. minnesota strains that expressed this epitope. These studies demonstrate that conserved LOS epitope(s) exist among different species and genera of non-enteric human pathogens and that different genetic mechanisms may have evolved in these pathogens to assemble some of these conserved epitopes.

OBJECTIVE

To evaluate community-provided trauma-focused cognitive behavior therapy (TF-CBT) compared with usual community treatment for children with intimate partner violence (IPV)-related posttraumatic stress disorder (PTSD) symptoms.

METHODS

Randomized controlled trial conducted using blinded evaluators.

METHODS

Recruitment, screening, and treatment were conducted at a community IPV center between September 1, 2004, and June 30, 2009.

METHODS

Of 140 consecutively referred 7- to 14-year-old children, 124 participated.

METHODS

Children and mothers were randomly assigned to receive 8 sessions of TF-CBT or usual care (child-centered therapy).

METHODS

Total child PTSD symptoms assessed using child and parent structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version [K-SADS-PL]) and self-report (University of California at Los Angeles PTSD Reaction Index [RI]). Secondary child outcomes were scores on the K-SADS-PL (PTSD symptom clusters), Screen for Child Anxiety Related Emotional Disorders (SCARED) (anxiety), Children's Depression Inventory (depression), Kaufman Brief Intelligence Test (cognitive functioning), and Child Behavior Checklist (total behavior problems).

RESULTS

Intent-to-treat analysis using last observation carried forward showed superior outcomes for TF-CBT on the total K-SADS-PL (mean difference, 1.63; 95% confidence interval [CI], 0.44-2.82), RI (mean difference, 5.5; 95% CI, 1.37-9.63), K-SADS-PL hyperarousal (mean difference, 0.71; 95% CI, 0.22-1.20), K-SADS-PL avoidance (0.55; 0.07-1.03), and SCARED (mean difference, 5.13; 95% CI, 1.31-8.96). Multiple imputation analyses confirmed most of these findings. The TF-CBT completers experienced significantly greater PTSD diagnostic remission (χ(2) = 4.67, P = .03) and had significantly fewer serious adverse events.

CONCLUSIONS

Community TF-CBT effectively improves children's IPV-related PTSD and anxiety.

BACKGROUND

clinicaltrials.gov Identifier: NCT00183326.

We describe a methodology for assigning individual estimates of long-term average air pollution concentrations that accounts for a complex spatio-temporal correlation structure and can accommodate spatio-temporally misaligned observations. This methodology has been developed as part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study funded by the U.S. EPA to investigate the relationship between chronic exposure to air pollution and cardiovascular disease. Our hierarchical model decomposes the space-time field into a "mean" that includes dependence on covariates and spatially varying seasonal and long-term trends and a "residual" that accounts for spatially correlated deviations from the mean model. The model accommodates complex spatio-temporal patterns by characterizing the temporal trend at each location as a linear combination of empirically derived temporal basis functions, and embedding the spatial fields of coefficients for the basis functions in separate linear regression models with spatially correlated residuals (universal kriging). This approach allows us to implement a scalable single-stage estimation procedure that easily accommodates a significant number of missing observations at some monitoring locations. We apply the model to predict long-term average concentrations of oxides of nitrogen (NOx) from 2005-2007 in the Los Angeles area, based on data from 18 EPA Air Quality System regulatory monitors. The cross-validated R2 is 0.67. The MESA Air study is also collecting additional concentration data as part of a supplementary monitoring campaign. We describe the sampling plan and demonstrate in a simulation study that the additional data will contribute to improved predictions of long-term average concentrations.

BACKGROUND

Hypernatremia is common in the intensive care unit (ICU). We assessed the prevalence of hypernatremia and its impact on mortality and ICU length of stay (LOS).

METHODS

Retrospective analysis.

METHODS

All patients admitted to a medical ICU of a university hospital during a 35-month observation period.

METHODS

Hypernatremia (serum sodium>> 149 mmol/L) after admission to the ICU.

METHODS

Main outcomes were 28-day hospital mortality and ICU LOS. Demographic factors, main diagnosis, and severity of illness. Cox proportional hazards regression models were used for data analysis.

RESULTS

Of 981 patients, 90 (9%) had hypernatremia, on admission to the ICU in 21 (2%) and developed during the ICU stay in 69 patients (7%). Of these 981 patients, 235 (24%) died; LOS was 8 +/- 9 (SD) days. Mortality rates were 39% and 43% in patients with hypernatremia on admission or that developed after admission compared with 24% in patients without hypernatremia (P < 0.01). LOS was 20 +/- 16 days in patients with hypernatremia compared with 8 +/- 10 days in patients without hypernatremia (P < 0.001). In multivariable analysis, hypernatremia was an independent risk factor for mortality (relative risk, 2.1; 95% confidence interval, 1.4 to 3.3).

CONCLUSIONS

Retrospective design, absence of data for long-term mortality.

CONCLUSIONS

Most cases of hypernatremia in the ICU developed after admission, suggesting an iatrogenic component in its evolution. Hypernatremia is associated with increased mortality. Strategies for preventing hypernatremia in the ICU should be encouraged.

Arachidonic acid is released by phospholipase A(2) and converted into hundreds of distinct bioactive mediators by a variety of cyclooxygenases (COX), lipoxygenases (LO), and cytochrome P450s. Because of the size and diversity of the eicosanoid class of signaling molecules produced, a thorough and systematic investigation of these biological processes requires the simultaneous quantitation of a large number of eicosanoids in a single analysis. We have developed a robust liquid chromatography/tandem mass spectrometry method that can identify and quantitate over 60 different eicosanoids in a single analysis, and we applied it to agonist-stimulated RAW264.7 murine macrophages. Fifteen different eicosanoids produced through COX and 5-LO were detected either intracellularly or in the media following stimulation with 16 different agonists of Toll-like receptors (TLR), G protein-coupled receptors, and purinergic receptors. No significant differences in the COX metabolite profiles were detected using the different agonists; however, we determined that only agonists creating a sustained Ca(2+) influx were capable of activating the 5-LO pathway in these cells. Synergy between Ca(2+) and TLR pathways was detected and discovered to be independent of NF-kappaB-induced protein synthesis. This demonstrates that TLR induction of protein synthesis and priming for enhanced phospholipase A(2)-mediated eicosanoid production work through two distinct pathways.

Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric repeats onto the 3' ends of eukaryotic chromosomes. Activation of telomerase may prevent telomeric shortening and correlates with cell immortality in the germline and certain tumor cells. Candidate hematopoietic stem cells (HSC) from adult bone marrow express low levels of telomerase, which is upregulated with proliferation and/or differentiation. To address this issue, we stimulated purified candidate HSC from human adult bone marrow with stem cell factor (SCF), interleukin-3 (IL-3), and Flt3-ligand (FL). After 5 days in culture, activity was detected in total cell extracts from IL-3-, SCF + FL-, SCF + IL-3-, FL + IL-3-, and SCF + IL-3 + FL-stimulated cultures, but not from cells cultured in SCF or FL alone. Within the CD34(+) fraction of the cultured cells, significant activity was found in the CD34(+)CD71(+) fraction. In addition, PKH26 staining confirmed that detectable telomerase activity was present in dividing PKH26(lo) cells, whereas nondividing PKH26(hi) cells were telomerase negative. Because in these experiments no distinction could be made between cycling "candidate" stem cells that had retained or had lost self-renewal properties, fetal liver cells with a CD34(+)CD38(-) phenotype, highly enriched for cycling stem cells, were also examined and found to express readily detectable levels of telomerase activity. Given the replication-dependent loss of telomeric DNA in hematopoietic cells, these observations suggest that the observed telomerase activity in candidate stem cells is either expressed in a minor subset of stem cells or, more likely, is not sufficient to prevent telomere shortening.

Common variable immunodeficiency (CVID) is characterized by a severe hypogammaglobulinemia. While the clinical picture is dominated by recurrent respiratory and gastrointestinal infections, a subgroup of up to 30% of the patients develops additional autoimmune phenomena, including thrombocytopenia and autoimmune hemolytic anemia. So far no classification allowed a prediction of the coincidence of immunodeficiency and autoimmunity. Here, we propose the size of the peripheral CD19(hi)CD2(lo/neg) B cell pool as a marker for CVID patients with autoimmune cytopenia and splenomegaly. Interestingly similar B cell populations are also found in patients with SLE and may not only be an epiphenomenon of the disease.

Controversy exists whether high frequency oscillatory ventilation with an active expiratory phase (HFO-A) should be used at low ventilator pressures or high alveolar volumes to minimize lung injury in the atelectasis-prone lung. We therefore ventilated 20 anesthetized, tracheostomized rabbits made surfactant-deficient by lung lavage in 1 of 3 ways: HFO-A at a high lung volume (HFO-A/HI), HFO-A at a low lung volume (HFO-A/LO), or conventional mechanical ventilation (CMV); all received 100% oxygen for 7 h. We examined oxygenation, lung mechanics, and lung pathology. Arterial oxygenation in the HFO-A/HI rabbits was kept greater than 350 mm Hg. Mean lung volume above FRC in these animals was 23.4 ml/kg. In rabbits ventilated with HFO-A/LO and CMV, arterial oxygen tensions were 70 to 100 mm Hg. Mean lung volumes were 7.8 and 4.3 ml/kg, respectively. Total respiratory system pressure-volume curves (P-V curves) showed no change from baseline in the HFO-A/HI group after 7 h of ventilation. The low lung volume groups (HFO-A/LO and CMV) showed a diminution in hysteresis of their P-V curves, lower total respiratory system compliance, more hyaline membranes and severe airway epithelial damage. (All changes significant with p less than 0.05). We conclude that maintenance of alveolar volume is a key mechanism in the prevention of lung injury during mechanical ventilation of the atelectasis-prone lung. For optimal outcome using high frequency oscillatory ventilation, alveoli must be actively reexpanded and then kept expanded using appropriate mean airway pressures.

BACKGROUND

Although the early use of a risk stratification score in upper GI bleeding is recommended, existing risk scores are not widely used in clinical practice.

OBJECTIVE

We sought to develop and validate an easily calculated bedside risk score, AIMS65, by using data routinely available at initial evaluation.

METHODS

Data from patients admitted from the emergency department with acute upper GI bleeding were extracted from a database containing information from 187 U.S. hospitals. Recursive partitioning was applied to derive a risk score for in-hospital mortality by using data from 2004 to 2005 in 29,222 patients. The score was validated by using data from 2006 to 2007 in 32,504 patients. Accuracy to predict mortality was assessed by the area under the receiver operating characteristic (AUROC) curve.

METHODS

Mortality, length of stay (LOS), and cost of admission.

RESULTS

The 5 factors present at admission with the best discrimination were albumin less than 3.0 g/dL, international normalized ratio greater than 1.5, altered mental status, systolic blood pressure 90 mm Hg or lower, and age older than 65 years. For those with no risk factors, the mortality rate was 0.3% compared with 31.8% in patients with all 5 (P < .001). The model had a high predictive accuracy (AUROC = 0.80; 95% CI, 0.78-0.81), which was confirmed in the validation cohort (AUROC = 0.77, 95% CI, 0.75-0.79). Longer LOS and increased costs were seen with higher scores (P < .001).

CONCLUSIONS

Database data used does not include outcomes such as rebleeding.

CONCLUSIONS

AIMS65 is a simple, accurate risk score that predicts in-hospital mortality, LOS, and cost in patients with acute upper GI bleeding.

CD223 (LAG-3) is an activation-induced cell surface molecule, structurally similar to the T cell coreceptor CD4, that binds MHC class II molecules with high affinity. Little is known about the expression and function of murine CD223. Here, we show that mRNA expression is restricted to the thymic medulla, splenic red pulp and sparse cells in the adult brain cortex. In contrast, surprisingly high expression was seen in defined tracts at the base of the cerebellum and in the choroid plexus of day 7 postnatal brain. mCD223:Ig, but not CD4:Ig, fusion proteins stained cells expressing MHC class II molecules. Analysis of mCD223 cell surface expression was performed with a new monoclonal antibody (mAb) that recognizes an epitope in the D2 domain. Although it blocked mCD223 function in vitro, it did not block binding of mCD223 to MHC class II molecules. While very few TCRalpha beta T cells in the spleen and thymus of naive mice express surface mCD223 (<3 %), approximately 18 % TCR gamma delta T cells and approximately 10 % NK cells are positive. This small population of TCRalpha beta T cells are cycling memory T cells (BrdU(+), CD44(hi), CD62L(lo)). In contrast, all T cells express mCD223 2-3 days post activation. This study and the anti-CD223 mAb should greatly assist in the elucidation of CD223 function.

BACKGROUND

Cardiovascular implantable electronic device (CIED) therapy can reduce morbidity and mortality, but this benefit can be diminished by CIED infection. Currently, there are limited published data on the mortality and cost associated with CIED infection.

METHODS

We analyzed the risk-adjusted total and incremental admission mortality, long-term mortality, admission length of stay (LOS), and admission cost associated with infection in a retrospective cohort of 200 219 Medicare fee-for-service patients admitted for CIED generator implantation, replacement, or revision between January 1, 2007, and December 31, 2007.

RESULTS

There were a total of 5817 admissions with infection. Infection was associated with significant increases in adjusted admission mortality (rate ratios, 4.8-7.7; standardized rates, 4.6%-11.3%) and long-term mortality (rate ratios, 1.6-2.1; standardized rates, 26.5%-35.1%), depending on CIED type. Importantly, approximately half of the incremental long-term mortality occurred after discharge. The adjusted LOS was significantly longer with infection (length of stay mean ratios, 2.5-4.0; standardized length of stay, 15.5-24.3 days), depending on CIED type. The standardized adjusted incremental and total admission costs with infection were $14 360 to $16 498 and $28 676 to $53 349, respectively, depending on CIED type. The largest incremental cost with infection was intensive care, which accounted for more than 40% of the difference. Adjusted long-term mortality rate and cost ratios with infection were significantly greater for pacemakers than for implantable cardioverter/defibrillators or cardiac resynchronization therapy/defibrillator devices.

CONCLUSIONS

Infection associated with CIED procedures resulted in substantial incremental admission mortality and long-term mortality that varied with the CIED type and occurred, in part, after discharge. Almost half of the incremental admission cost was for intensive care.

Collective efficacy, i.e., perception of mutual trust and willingness to help each other, is a measure of neighborhood social capital and has been associated with positive health outcomes including lower rates of assaults, homicide, premature mortality, and asthma. Collective efficacy is frequently considered a "cause", but we hypothesized that environmental features might be the foundation for or the etiology of personal reports of neighborhood collective efficacy. We analyzed data from the Los Angeles Family and Neighborhood Study (LAFANS) together with geographical data from Los Angeles County to determine which social and environmental features were associated with personal reports of collective efficacy, including presence of parks, alcohol outlets, elementary schools and fast food outlets. We used multi-level modeling controlling for age, education, annual family income, sex, marital status, employment and race/ethnicity at the individual level. At the tract level, we controlled for tract-level disadvantage, the number of off-sale alcohol outlets per roadway mile, the number of parks and the number of fast food outlets within the tract and within 1/2 mile of the tract's boundaries. We found that parks were independently and positively associated with collective efficacy; alcohol outlets were negatively associated with collective efficacy only when tract-level disadvantage was not included in the model. Fast food outlets and elementary schools were not linearly related to collective efficacy. Certain environmental features may set the stage for neighborhood social interactions, thus serving as a foundation for underlying health and well-being. Altering these environmental features may have greater than expected impact on health.

OBJECTIVE

We aimed to quantify the frequency and nature of early complications after implantable cardioverter-defibrillator (ICD) implantation in general practice, and estimate the incremental costs of those complications to the health care system.

BACKGROUND

Cardioverter-defibrillator implantation rates are rising quickly. Little has been published regarding the outcomes and costs of these procedures in unselected populations.

METHODS

Using Medicare Provider Analysis and Review (MedPAR) files, we identified 30,984 admissions containing procedure codes for new ICD or cardiac resynchronization therapy defibrillator implantation in fiscal year 2003. The frequencies of eight complicating diagnoses during these admissions were determined. Length of stay (LOS) and total hospital costs, derived using whole-hospital cost to charge ratios, were calculated for each admission. The incremental effects of any and each complication on LOS and hospital cost were estimated in multivariable models, adjusting for demographic factors and comorbid conditions.

RESULTS

The mean cost for all admissions was 42,184 dollars (median 37,902 dollars) with mean LOS of 4.7 days (median 2.0 days). One or more complications were coded in 10.8% of admissions, most commonly "mechanical complication of the ICD" and hemorrhage/hematoma. The occurrence of any complication increased adjusted LOS by 3.4 days and costs by 7,251 dollars. Each of the individual complications was associated with highly significant increases in both LOS (1 to 10 days) and hospital cost (5,000 dollars to 20,000 dollars).

CONCLUSIONS

In fiscal 2003, 10.8% of Medicare patients undergoing cardioverter-defibrillator implantation experienced one or more early complications, associated with significant increases in LOS and costs. Efforts to reduce these complications could have significant clinical and financial benefits.

Macrophages promote both injury and repair after myocardial infarction, but discriminating functions within mixed populations remains challenging. Here we used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4⁺LYVE1⁺MHC-II^loCCR2^- resident cardiac macrophages self-renew with negligible blood monocyte input. Monocytes partially replaced resident TIMD4^-LYVE1^-MHC-II^hiCCR2^- macrophages and fully replaced TIMD4^-LYVE1^-MHC-II^hiCCR2⁺ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets. Ischemic injury reduced TIMD4⁺ and TIMD4^- resident macrophage abundance, whereas CCR2⁺ monocyte-derived macrophages adopted multiple cell fates within infarcted tissue, including those nearly indistinguishable from resident macrophages. Recruited macrophages did not express TIMD4, highlighting the ability of TIMD4 to track a subset of resident macrophages in the absence of fate mapping. Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, revealing a nonredundant, cardioprotective role of resident cardiac macrophages.

OBJECTIVE

Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.

METHODS

We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis.

RESULTS

We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI.

CONCLUSIONS

Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

BACKGROUND

This report describes the unusually high response rate of metastatic synovial sarcoma to high dose ifosfamide (14-18 g/m2) when that drug was used to treat 13 consecutive patients with recurrent metastatic synovial sarcoma before surgery (or thoracotomies) to provide optimal salvage therapy for these patients.

METHODS

Thirteen patients with recurrent or pulmonary metastatic synovial sarcoma seen at the Cedars-Sinai Comprehensive Cancer Center (Los Angeles, CA) from April, 1989 through January, 1993 were treated with high dose ifosfamide (14-18 g/m2). Ifosfamide was infused at the dose of 2 g/m2 over a 4-hour bolus infusion, followed by 2-g/m2 24-hour continuous infusions of ifosfamide, for a total of 14 or 18 g/m2 (6-8 days). Mesna (Mesnex, Bristol-Myers Oncology, Princeton, NJ) was infused with the ifosfamide at equimolar doses. Supplemental sodium bicarbonate (180 mEq) was given daily to prevent severe acidosis. Nine of the thirteen patients were treated with prior chemotherapy for their primary tumors. Prior chemotherapy consisted of doxorubicin (Adriamycin, Adria Labs, Dublin, OH) in all patients and doxorubicin combined with cisplatin in eight of them.

RESULTS

All 13 patients had objective responses to high dose ifosfamide chemotherapy. There were nine partial responses and four complete responses. Five of the patients died of disease at 20-40 months (median, 27 months) from initial therapy. Eight patients have survived from 2 to 43 months (median, 20 months) from initial therapy, and three of these patients are disease free. Those patients surviving disease free had successful surgical removal of their residual metastatic disease after chemotherapy.

CONCLUSIONS

Metastatic synovial sarcoma appears to be particularly sensitive to high dose ifosfamide chemotherapy. This experience suggests that there is a role for high dose ifosfamide chemotherapy in preoperative and postoperative adjuvant chemotherapy for primary synovial sarcoma, which is usually always a high grade malignant lesion with a poor prognosis after surgery alone.

BACKGROUND

In ambulatory care settings, patients with limited English proficiency receive lower quality of care. Limited information is available describing outcomes for inpatients.

OBJECTIVE

To investigate the effect of English proficiency on length of stay (LOS) and in-hospital mortality.

METHODS

Retrospective analysis of administrative data at 3 tertiary care teaching hospitals (University Health Network) in Toronto, Canada.

METHODS

Consecutive inpatient admissions from April 1993 to December 1999 were analyzed for LOS differences first by looking at 23 medical and surgical conditions (59,547 records) and then by a meta-analysis of 220 case mix groups (189,119 records). We performed a similar analysis for in-hospital mortality.

METHODS

LOS and odds of in-hospital death for limited English-proficient (LEP) patients relative to English-proficient (EP) patients.

RESULTS

LEP patients stayed in hospital longer for 7 of 23 conditions (unstable coronary syndromes and chest pain, coronary artery bypass grafting, stroke, craniotomy procedures, diabetes mellitus, major intestinal and rectal procedures, and elective hip replacement), with LOS differences ranging from approximately 0.7 to 4.3 days. A meta-analysis using all admission data demonstrated that LEP patients stayed 6% (approximately 0.5 days) longer overall than EP patients (95% confidence interval, 0.04 to 0.07). LEP patients were not at increased risk of in-hospital death (relative odds, 1.0; 95% confidence interval, 0.9 to 1.1).

CONCLUSIONS

Patients with limited English proficiency have longer hospital stays for some medical and surgical conditions. Limited English proficiency does not affect in-hospital mortality. The effect of communication barriers on outcomes of care in the inpatient setting requires further exploration, particularly for selected conditions in which length of stay is significantly prolonged.

BACKGROUND

12/15-lipoxygenase (12/15-LO) activity leads to the production of the proinflammatory eicosanoids 12-S-hydroxyeicosatetraenoic acid (12SHETE) and 13-S-hydroxyoctadecadienoic acid. We have previously shown a 3.5-fold increase in endothelial intercellular adhesion molecule (ICAM)-1 expression in mice overexpressing the 12/15-LO gene. We examined whether 12/15-LO activity regulated endothelial ICAM-1 expression.

RESULTS

Freshly isolated aortic endothelial cells (EC) from 12/15-LO transgenic mice had significantly greater nuclear factor-kappaB (NF-kappaB) activation and ICAM mRNA expression compared with C57BL/6J control. 12/15-LO transgenic EC showed elevated RhoA activity, and inhibition of RhoA using either C3 toxin or the Rho-kinase inhibitor Y-27632 blocked NF-kappaB activation, ICAM-1 induction, and monocyte adhesion. Furthermore, we show that 12SHETE activates protein kinase Calpha, which forms a complex with active RhoA and is required for NF-kappaB-dependent ICAM expression in response to 12SHETE.

CONCLUSIONS

The 12/15-LO pathway stimulates ICAM-1 expression through the RhoA/protein kinase Calpha-dependent activation of NF-kappaB. These findings identify a major signaling pathway in EC through which 12/15-LO contributes to vascular inflammation and atherosclerosis.

Based on experimental and epidemiological evidence it is hypothesized that estrogen increases breast cancer risk by increasing mitotic activity in breast epithelial cells. Aromatase is crucial to the biosynthesis of estrogens and may therefore play a role in breast cancer development. Supporting data for an etiological role of aromatase in breast tumor biology are several-fold. First, the association between weight and postmenopausal breast cancer risk may be mediated by aromatase. Secondly, a pilot study found a higher aromatase expression in normal breast adipose tissue from breast cancer cases as opposed to healthy women. Thirdly, experimental data in animals suggest that aromatase activity predisposes mammary tissue to preneoplastic and neoplastic changes. In a multiethnic cohort study conducted in Los Angeles and on Hawaii we investigated (i) whether the plasma estrone to androstenedione (E1/A) ratio in different ethnic groups was associated with ethnic differences in breast cancer incidence, and (ii) whether genetic variation in the CYP19 gene encoding the P450 aromatase protein was associated with breast cancer risk. The age- and weight-adjusted ethnic specific E1/A ratios x 100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09). The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far. We found no consistent association of an intronic (TTTA)n repeat polymorphism with breast cancer risk in different ethnic groups. This polymorphism was not associated with differences in the plasma E1/A ratio in a way that would predict its functional relevance. We describe a newly identified TTC deletion in intron 5 of the CYP19 gene that is associated with the (TTTA)n repeat polymorphism. Neither this polymorphism, nor a polymorphism at codon 264 in exon VII of the CYP19 gene, was associated with breast cancer. We did not identify any genetic variation in exon VIII in 54 African-American subjects. We identified rare genetic variants of unknown functional relevance in the promoter 1.4 of the CYP19 gene in 3 out of 24 Latina women. Further investigation into the role of aromatase in breast cancer etiology is important, given that the potential use of aromatase inhibitors as breast cancer chemopreventives depends on these results.

BACKGROUND

The USA300 methicillin resistant Staphylococcus aureus (MRSA) genetic background has rapidly emerged as the predominant cause of community-associated S. aureus infections in the U.S. However, epidemiologic characteristics of S. aureus household transmission are poorly understood.

METHODS

We performed a cross-sectional study of adults and children with S. aureus skin infections and their household contacts in Los Angeles and Chicago. Subjects were surveyed for S. aureus colonization of the nares, oropharynx, and inguinal region and risk factors for S. aureus disease. All isolates underwent genetic typing.

RESULTS

We enrolled 1162 persons (350 index patients and 812 household members). The most common infection isolate characteristic was ST8/SCCmec IV, PVL+ MRSA (USA300) (53%). S. aureus colonized 40% (137/350) of index patients and 50% (405/812) of household contacts. A nares-only survey would have missed 48% of S. aureus and 51% of MRSA colonized persons. Sixty-five percent of households had >1 S. aureus genetic background identified and 26% of MRSA isolates in household contacts were discordant with the index patients' infecting MRSA strain type. Factors independently associated (P < .05) with the index strain type colonizing household contacts were recent skin infection, recent cephalexin use, and USA300 genetic background.

CONCLUSIONS

In our study population, USA300 MRSA appeared more transmissible among household members compared with other S. aureus genetic backgrounds. Strain distribution was complex; >1 S. aureus genetic background was present in many households. S. aureus decolonization strategies may need to address extra-nasal colonization and the consequences of eradicating S. aureus genetic backgrounds infrequently associated with infection.

Within the capsule gene complex (cps) of Neisseria meningitidis B a 5.5 kb DNA fragment encodes proteins with strong homologies to enzymes of the lipopolysaccharide biosynthetic pathway of Salmonella typhimurium and Escherichia coli, GalE, RfbB, RfbC and RfbD. A meningococcal galE mutant expressed a truncated lipooligosaccharide (LOS), which terminated at the glucose residue between inner and outer core, and a second galE gene present outside the cps cluster was found to be transcriptionally and functionally inactive and, thus, unable to complement this defect. Because of the defect in the outer core, the LOS of the galE-defective meningococcal mutant was not sialylated. In contrast, carbohydrate analysis of the LOS of an rfb-defective meningococcal mutant revealed no difference from the LOS of the wild-type strain, suggesting that the rfb genes are inactive. This was supported by Northern blot analysis, which showed that expression of the rfb gene products was transcriptionally regulated. The inability of the meningococcal galE mutant, which cannot sialylate the LOS, allowed us to investigate the significance of LOS sialylation in relation to the presence of the polysialic acid capsule. Sialylated LOS, but not the polysialic acid capsule, is necessary to confer complete serum resistance on the meningococcus by inhibition of the alternative complement pathway.

15-Lipoxygenase (15-LO) catalyzes hydroperoxidation of fatty acids, a reaction of potential relevance to inflammation, membrane remodeling, and atherosclerosis. In human leukocytes, 15-lipoxygenation of arachidonic acid produces 15-(S)-hydroxyeicosatetraenoic acid and lipoxin A4, which suppress white cell chemotaxis, adherence, and activation, and antagonize proinflammatory leukotrienes. Interleukin (IL)-13, produced by T-helper subset 2 (TH-2) lymphocytes, specifically and potently induced 15-LO gene expression and enzyme activity in human monocytes. Among other TH-2 lymphokines, this induction of 15-LO is shared by IL-4 but not by IL-10. Interferon-gamma, a product of TH-1 lymphocytes, blocked IL-13-mediated induction of 15-LO. The induction of the anti-inflammatory 15-LO pathway by IL-13 reveals a new facet of IL-13 biology that supports its role as a cytokine with potential to down-regulate inflammatory pathways. The contrasting effects of interferon-gamma and IL-13 on 15-LO induction demonstrate mechanisms by which T-lymphocyte subsets may modulate macrophage/monocyte function in inflammation or atherosclerosis.

BACKGROUND

Preclinical data indicate that docetaxel, platinum salts, and the combination of both drugs are highly synergistic with the anti-HER2 antibody trastuzumab. The University of California at Los Angeles-Oncology Research Network (UCLA-ORN) and the Breast Cancer International Research Group (BCIRG) have conducted two phase II studies to evaluate docetaxel and trastuzumab in combination with either cisplatin or carboplatin for the treatment of women with advanced breast cancer that overexpresses HER2.

METHODS

Each study enrolled 62 patients with HER2-overexpressing tumors. Patients received a median of six cycles of docetaxel at 75 mg/m2 of body surface area and cisplatin (BCIRG 101 study) at 75 mg/m2 or carboplatin (UCLA-ORN study) at AUC = 6 mg/mL. min given on day 1 and then every 21 days. Trastuzumab was given on day 1, cycle 1 (4 mg/kg) and then continued weekly at 2 mg/kg for 1 year or until disease progression. Tumor measurements were obtained at baseline, after three cycles of chemotherapy, and then every 3 months. HER2 gene amplification was determined by fluorescence in situ hybridization.

RESULTS

Patient characteristics were comparable between trials with the exception that 15% of the patients in the UCLA-ORN study had received previous adjuvant taxane therapy. Both regimens were well tolerated, with manageable toxicities. Hematologic toxicities were more frequent in patients in the UCLA-ORN study than in patients in the BCIRG 101 study, whereas the reverse pattern was observed for non-hematologic toxicities. One patient in each study developed reversible congestive heart failure. Responses were observed in 49 of 62 patients in the BCIRG 101 study (overall response rate = 79%, 95% confidence interval [CI] = 66% to 89%) and in 34 of 59 evaluable patients in the UCLA-ORN study (overall response rate = 58%, 95% CI = 44% to 70%). Median times to progression were 9.9 months (95% CI = 8.3 to 13.1 months) and 12.7 months (95% CI = 8.6 to 15.5 months) for patients in the BCIRG 101 and UCLA-ORN studies, respectively. Overall response rates were higher and median time to progression was longer in the subset of patients whose tumors harbored HER2 gene amplification.

CONCLUSIONS

Combinations of docetaxel, a platinum salt, and trastuzumab are feasible and active in patients with advanced breast cancers that overexpress HER2. The BCIRG is conducting ongoing randomized studies of the three-drug combination in both the metastatic and adjuvant settings.