Usefulness of high-sensitivity C-reactive protein to predict mortality in patients with atrial fibrillation (from the Atherosclerosis Risk In Communities [ARIC] Study)

High-sensitivity C-reactive protein (hs-CRP) is a marker for the risk of cardiovascular and overall mortality. However, information about the association between hs-CRP and mortality in patients with atrial fibrillation is scarce. A total of 293 participants of the Atherosclerosis Risk In Communities study with a history of AF and hs-CRP levels available were studied. During a median follow-up of 9.4 years, 134 participants died (46%). The hazard ratio of all-cause mortality associated with the highest versus the lowest tertile of hs-CRP was 2.52 (95% confidence interval 1.49 to 4.25) after adjusting for age, gender, history of cardiovascular diseases, and cardiovascular risk factors. A similar trend was observed for cardiovascular mortality (57 events; hazard ratio 1.90, 95% confidence interval 0.81 to 4.45). The Congestive heart failure, Hypertension, Age >75 years, Diabetes, and previous Stroke or transient ischemic attack (CHADS2) score was also associated with all-cause and cardiovascular mortality, with an adjusted hazard ratio of 3.39 (95% confidence interval 1.91 to 6.01) and 8.71 (95% confidence interval 2.98 to 25.47), respectively, comparing those with a CHADS2 score >2 versus a CHADS2 score of 0. Adding hs-CRP to a predictive model including the CHADS2 score was associated with an improvement of the C-statistic for total mortality (from 0.627 to 0.677) and for cardiovascular mortality (from 0.700 to 0.718). In conclusion, high levels of hs-CRP constitute an independent marker for the risk of mortality in patients with atrial fibrillation.     

Successful daptomycin treatment for Staphylococcus lugdunensis endocarditis

Staphylococcus lugdunensis, a coagulase-negative Staphylococcus species, is an increasingly relevant pathogen in the clinical setting. The organism has been isolated as a source of multiple clinical manifestations, including endocarditis. Herein, the authors present 2 cases of Staphylococcus lugdunensis endocarditis. These cases demonstrate the enhanced virulence and wide range of disease severity this organism creates. This enhanced virulence, undoubtedly present in these cases, led to novel daptomycin antibiotic regimen. To the best of the authors knowledge, these are the first reported cases using daptomycin in the treatment of Staphylococcus lugdunensis endocarditis.     

Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity

Natural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. This effect is achieved through a complex mosaic of inhibitory and activating receptors expressed by NK cells that ultimately determine the magnitude of the NK-cell response. The T-cell immunoglobulin- and mucin domain-containing (Tim)-3 receptor was initially identified as a T-helper 1-specific type I membrane protein involved in regulating T-cell responses. Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. Tim-3 protein is expressed on essentially all mature CD56(dim)CD16(+) NK cells and is expressed heterogeneously in the immature CD56(bright)CD16(-) NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56(bright)CD16(-) NK cells after stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a maturation marker on NK cells. Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. However, when Tim-3 was cross-linked with antibodies it suppressed NK cell-mediated cytotoxicity. These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3.     

Older Adult Norms for the Southern California Figure-Ground Visual Perception Test

Older adult norms for men are provided for the Southern California Figure-Ground Visual Perception Test (FG; Ayres, 1966), based on the performance of 117 patients from a geriatric medicine and rehabilitation facility ranging in age from 40 to 77 years. Reasons are presented for administering the entire test rather than using the traditional cutoff. When comparing FG performance to norms of younger adults (Bieliauskas, Newberry, Gerstenberger, 1988), results indicate that figure-ground discrimination is poorer in older individuals. The norms provided here serve to complement the previous study employing FG, and it is hoped that they will encourage its wider use.     

The impact of race on outcomes following emergency surgery: an American College of Surgeons National Surgical Quality Improvement Program assessment

Background

Despite significant evolutions in health care, outcome discrepancies exist among demographic cohorts. We sought to determine the impact of race on emergency surgery outcomes.

Methods

This is a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2005 through 2009) for all patients aged ≥16 years undergoing emergency abdominal surgery. Primary outcomes included morbidity and mortality.

Results

We identified 75,280 patients (mean age 48.2 ± 19.9 years, 51.7% female; 79% white, 9.9% black, 5.0% Hispanic, 3.7% Asian, 1.3% American Indian or Alaskan, .2% Pacific Islander). Annual rates of emergency operations ranged from 7.3% to 8.5% (P = .22). The overall complication (18.6%) and mortality rate (4.6%) was highest in the black population (24.3%, 5.3%) followed by whites (18.7%, 4.6%), with the lowest rate in Hispanic (11.7%, 1.8%) and Pacific Islander populations (10.2%, 1.8%; P < .001). Compared with whites, blacks had a 1.25-fold (1.17 to 1.34; P < .001) increased risk of complications, but similar mortality (P = .168). When combining minorities, overall complications were 1.059-fold (1.004 to 1.12; P = .034) higher, however, mortality was reduced 1.7-fold (1.07 to 1.34; P = .001).

Conclusions

Following emergency abdominal surgery, minority race is independently associated with increased complications and reduced mortality.     

The pediatric surgeon's road to research independence: utility of mentor-based National Institutes of Health grants

Background

The current research environment for academic surgeons demands that extramural funding be obtained. Financial support from the National Institutes of Health (NIH) is historically the gold standard for funding in the biomedical research community, with the R01 funding mechanism viewed as indicator of research independence. The NIH also supports a mentor-based career development mechanism (K-series awards) in order to support early-stage investigators. The goal of this study was to investigate the grants successfully awarded to pediatric surgeon-scientists and then determine the success of the K-series award recipients at achieving research independence.

Methods

In July 2012, all current members of the American Pediatric Surgery Association (APSA) were queried in the NIH database from 1988–2012 through the NIH Research Portfolio Online Reporting Tools. The following factors were analyzed: type of grant, institution, amount of funding, and funding institute or center.

Results

Among current APSA members, there have been 83 independent investigators receiving grants, representing 13% of the current APSA membership, with 171 independent grants funded through various mechanisms. Six percent currently have active NIH funding, with $7.2 million distributed in 2012. There have been 28 K-series grants awarded. Of the recipients of expired K08 awards, 39% recipients were subsequently awarded an R01 grant. A total of 63% of these K-awarded investigators transitioned to an independent NIH award mechanism.

Conclusions

Pediatric surgeon-scientists successfully compete for NIH funding. Our data suggest that although the K-series funding mechanism is not the only path to research independence, over half of the pediatric surgeons who receive a K-award are successful in the transition to independent investigator.     

Progress toward a Staphylococcus aureus vaccine

High attack rates and the ability of Staphylococcus aureus to develop resistance to all antibiotics in medical practice heightens the urgency for vaccine development. S. aureus causes many disease syndromes, including invasive disease, pneumonia, and skin and soft tissue infections. It remains unclear whether a single vaccine could protect against all of these. Vaccine composition is also challenging. Active immunization with conjugated types 5 and 8 capsular polysaccharides, an iron scavenging protein, isdB, and passive immunization against clumping factor A and lipoteichoic acid have all proven unsuccessful in clinical trials. Many experts advocate an approach using multiple antigens and have suggested that the right combination of antigens has not yet been identified. Others advocate that a successful vaccine will require antigens that work by multiple immunologic mechanisms. Targeting staphylococcal protein A and stimulating the T-helper 17 lymphocyte pathway have each received recent attention as alternative approaches to vaccination in addition to the more traditional identification of opsonophagocytic antibodies. Many questions remain as to how to successfully formulate a successful vaccine and to whom it should be deployed.