National trends in Staphylococcus aureus infection rates: impact on economic burden and mortality over a 6-year period (1998-2003).

BACKGROUND: We evaluated historical trends in the Staphylococcus aureus infection rate, economic burden, and mortality in US hospitals from 1998 through 2003. METHODS: The Nationwide Inpatient Sample was used to assess trends over time of S. aureus infection during 1998-2003. Historical trends were determined for 5 strata of hospital stays, including all inpatient stays, surgical procedure stays, invasive cardiovascular surgical stays, invasive orthopedic surgical stays, and invasive neurosurgical stays. RESULTS: During the 6-year study period from 1998 through 2003, the rate of S. aureus infection increased significantly for all inpatient stays (from 0.74% to 1.0%; annual percentage change (APC), 7.1%; P=.004), surgical stays (from 0.90% to 1.3%; APC, 7.9%; P=.001), and invasive orthopedic surgical stays (from 1.2% to 1.8%; APC, 9.3%; P<.001). For invasive neurosurgical stays, the rate of S. aureus infection did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (from 1.4% to 1.8%; P=.034). The total economic burden of S. aureus infection for hospitals also increased significantly for all stay types, with the annual percentage increase ranging from 9.2% to 17.9% (P<.05 for all). In 2003, the total economic burden of S. aureus infection was estimated to be $14.5 billion for all inpatient stays and $12.3 billion for surgical patient stays. However, there were significant decreases in the risk of S. aureus-related in-hospital mortality from 1998 to 2003 for all inpatient stays (from 7.1% to 5.6%; APC, -4.6%; P=.001) and for surgical stays (from 7.1% to 5.5%; APC, -4.6%; P=.002). CONCLUSIONS: The inpatient S. aureus infection rate and economic burden of S. aureus infections for US hospitals increased substantially from 1998 to 2003, whereas the in-hospital mortality rate decreased.     

Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders

Upon the discovery of numerous genes involved in the pathogenesis of neurodevelopmental disorders, several studies showed that a significant proportion of these genes converge on common pathways and protein networks. Here, we used a reversed approach, by screening the AnkyrinG protein-protein interaction network for genetic variation in a large cohort of 1009 cases with neurodevelopmental disorders. We identified a significant enrichment of de novo potentially disease-causing variants in this network, confirming that this protein network plays an important role in the emergence of several neurodevelopmental disorders.Subject terms: Genetics research, Neurological disorders     

Health and disease as practical concepts: exploring function in context-specific definitions

Medicine, Health Care and Philosophy - Despite the longstanding debate on definitions of health and disease concepts, and the multitude of accounts that have been developed, no consensus has been...     

Three-Dimensional Model-Based Segmentation in Echocardiography Using High Temporal Tissue and Blood Flow Information

Accurate 3-D surface segmentation is a challenging task in echocardiography because of the relatively low image quality. We introduce a new method for 3-D segmentation of the endocardium involving temporal decorrelation of echo signals originating from tissue and blood using radiofrequency (RF) signals acquired in 3-D Doppler mode. Temporal features were extracted in 3-D Doppler mode, where a sequence of RF lines is recorded for each image line. Each set of RF lines is highly correlated because of the high pulse repetition frequency. However, for high blood flow, the RF signals will decorrelate over time in contrast to the endocardium, which will remain relatively highly correlated over time. These decorrelation features permit differentiation between myocardial tissue and blood flow. We describe an implementation of a 3-D segmentation model in which temporal information is used as external constraint. The model was validated in a phantom and in vivo in healthy volunteers (n = 5). The phantom study revealed that the model successfully segmented the artificial blood lumen even for low flow velocity and illustrated the sensitivity of the segmentations to flow rate. In healthy volunteers, high Dice similarity indices indicate that 3-D segmentation of the endocardial border in vivo is feasible.     

From the Cover: Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors

Neutrophils are indispensable for clearing infections with the prominent human pathogen Staphylococcus aureus. Here, we report that S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G. The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range. Eap proteins are together essential for NSP inhibition by S. aureus in vitro and promote staphylococcal infection in vivo. The crystal structure of the EapH1/NE complex showed that Eap molecules constitute a unique class of noncovalent protease inhibitors that occlude the catalytic cleft of NSPs. These findings increase our insights into the complex pathogenesis of S. aureus infections and create opportunities to design novel treatment strategies for inflammatory conditions related to excessive NSP activity.Infections with the human pathogen Staphylococcus aureus constitute a major risk to human health. Although this bacterium harmlessly colonizes more than 30% of the population via the nose or skin, it causes severe morbidity and mortality upon invasion of deeper tissues (1). To avert these serious infections, neutrophils play an indispensable role (2). Neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CG), are important for various neutrophil functions. Active NSPs are stored within the azurophilic granules (3), but upon neutrophil activation, they either enter the nucleus to regulate extracellular trap (NET) formation (4) or they are released into the extracellular milieu to kill certain bacteria (5), cleave bacterial virulence factors (5, 6), or regulate immune responses by cleaving chemokines and receptors (7). Recently, a fourth neutrophil serine protease, denoted NSP4, was identified (8).Given the central role of NSPs in neutrophil function, we wondered whether S. aureus had evolved mechanisms to cope with NSPs. In this study, we discover that S. aureus secretes a family of proteins that specifically and potently block NSPs: extracellular adherence protein (Eap) and the hitherto functional orphans Eap-homologue (EapH) 1 and 2. Structural studies presented here show that Eap molecules represent a unique class of noncovalent NSP inhibitors that is distinct from the well-known chelonianin class of inhibitors. These mechanistic insights can initiate development of novel, broad-range NSP inhibitors to be used in various inflammatory conditions. Furthermore, these insights increase our understanding of the pathogenicity of S. aureus and underline the exceptional capability of this pathogen to adapt to its host by modulating the immune response.     

Hyaluronic Acid as a Marker of Hepatic Sinusoidal Obstruction Syndrome Secondary to Oxaliplatin-Based Chemotherapy in Patients with Colorectal Liver Metastases

Background

A considerable number of patients develop sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy for colorectal liver metastases (CLMs). SOS is associated with adverse outcomes after major hepatectomy. Hyaluronic acid (HA) is a marker of hepatic sinusoidal endothelial cell function and may serve as an accurate marker of SOS. This study aimed to assess the value of systemic HA levels and fractional extraction (FE) of HA by the splanchnic area and liver as markers of SOS after oxaliplatin-based chemotherapy for CLMs.

Methods

Forty patients were studied. The presence of SOS was assessed histopathologically. Blood samples from the radial artery and portal and hepatic veins were collected. HA levels were determined by ELISA and the FE of HA was estimated.

Results

SOS was present in 23 patients, 11 of whom demonstrated moderate or severe SOS. Preoperative HA levels were significantly higher in patients with moderate or severe SOS (group B, n = 11) compared to patients with no or mild SOS (group A, n = 29) (51.6 ± 10.2 ng/mL vs. 32.1 ± 3.5 ng/mL, p = 0.030). A cutoff HA level of 44.1 ng/mL yielded a sensitivity of 67 % and specificity of 83 % for detection of SOS. The positive predictive value was 50 % and the negative predictive value 91 %. Both groups exhibited a similar FE of HA by the splanchnic area (?7.9 ± 8.5 % in Group A vs. 7.3 ± 3.6 % in Group B, p = 0.422) and liver (?10.7 ± 6.2 % in Group A vs. 4.6 ± 2.3 % in Group B, p = 0.265).

Conclusions

Systemic HA levels can be used to detect patients at risk of SOS after oxaliplatin-based chemotherapy for CLMs. Additional investigations into the presence of SOS are indicated in patients with elevated HA levels.     

Predicting alcohol dependence from multi-site brain structural measures

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.