Anders Dahl

Enterococcus faecalis Infective Endocarditis A Pilot Study of the Relationship Between Duration of Gentamicin Treatment and Outcome

Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min (P=0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P<0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively (P=0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P=0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P=0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results.Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations.nnMethods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min ( P =0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P <0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively ( P =0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P =0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P =0.009) compared with those treated after 2007.nnConclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results.nn# Clinical Perspective {#article-title-50}

Effective image database search via dimensionality reduction

Image search using the bag-of-words image representation is investigated further in this paper. This approach has shown promising results for large scale image collections making it relevant for Internet applications. The steps involved in the bag-of-words approach are feature extraction, vocabulary building, and searching with a query image. It is important to keep the computational cost low through all steps. In this paper we focus on the efficiency of the technique. To do that we substantially reduce the dimensionality of the features by the use of PCA and addition of color. Building of the visual vocabulary is typically done using k-means. We investigate a clustering algorithm based on the leader follower principle (LF-clustering), in which the number of clusters is not fixed. The adaptive nature of LF-clustering is shown to improve the quality of the visual vocabulary using this. In the query step, features from the query image are assigned to the visual vocabulary. The dimensionality reduction enables us to do exact feature labeling using kD-tree, instead of approximate approaches normally used. Despite the dimensionality reduction to between 6 and 15 dimensions we obtain improved results compared to the traditional bag-of-words approach based on 128 dimensional SIFT feature and k-means clustering.

Clinical utility of 18 F-FDG positron emission tomography/computed tomography scan vs. 99m Tc-HMPAO white blood cell single-photon emission computed tomography in extra-cardiac work-up of infective endocarditis

The extra-cardiac work-up in infective endocarditis (IE) comprises a search for primary and secondary infective foci. Whether 18FDG-PET/CT or WBC-SPECT/CT is superior in detection of clinically relevant extra-cardiac manifestations in IE is unexplored. The objectives of this study were to identify the numbers of positive findings detected by each imaging modality, to evaluate the clinical relevance of these findings and to define the reproducibility for extra-cardiac foci in patients with definite IE. Each modality was evaluated for numbers and location of positive extra-cardiac foci in patients with definite IE. A team of 2u2009×u20092 cardiologists evaluated each finding to determine clinical relevance. Clinical utility was determined by 4 criteria converted into an ordinal scale. Using the manifestation with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. To evaluate reproducibility for each modality, an imaging core laboratory reviewed all findings. In 55 IE patients, 91 pathological foci were found by FDG-PET/CT and 37 foci were identified by WBC-SPECT/CT (pu2009<u20090.001). The clinical utility of FDG-PET/CT was significantly higher than that of WBC-SPECT/CT when comparing clinical utility score (2.06 vs. 1.17; pu2009=u20090.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for WBC-SPECT/CT (k 0.69, 95% CI 0.49–0.89) and substantial to excellent for FDG-PET/CT (k 0.79, 95% CI 0.61–0.98). FDG-PET/CT has a significantly higher clinical utility score than WBC SPECT/CT and is potentially superior to WBC-SPECT/CT in detection of extra-cardiac pathology in patients with IE.

Risk Factors of Endocarditis in Patients With Enterococcus faecalis Bacteremia: External Validation of the NOVA Score

BACKGROUNDnThe NOVA score is a recently developed diagnostic tool used to identify patients with increased risk of infective endocarditis (IE) among patients with Enterococcus faecalis bacteremia. We aimed to validate the NOVA score and to identify risk factors for IE.nnnMETHODSnFrom 1 January 2010 to 31 December 2013, we included 647 consecutive patients with E. faecalis bacteremia. The NOVA score was used in a slightly adapted form; 2/2 positive blood cultures resulted in 5 points, unknown origin of infection in 4 points, prior valve disease in 2 points, and heart murmur in 1 point.nnnRESULTSnIE was diagnosed in 78 patients (12%). Monomicrobial E. faecalis bacteremia (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.6-8.0), prosthetic heart valve (HR, 6.2; 95% CI, 3.8-10.1), male sex (HR, 2.0; 95% CI, 1.1-3.8), and community acquisition (HR, 1.8; 95% CI, 1.1-2.9) were independently associated with IE. The adapted NOVA score was applied in the 240 patients examined by echocardiography. A low score (<4) was found in 40 patients (17%), implying a low likelihood of IE. Of the 78 patients with IE, 76 had a high score (≥4), resulting in a sensitivity of 97%, specificity of 23%, a negative predictive value of 95%, and a positive predictive value of 38%.nnnCONCLUSIONSnMonomicrobial E. faecalis bacteremia, community acquisition, prosthetic heart valve, and male sex are associated with increased risk of IE. In our retrospective cohort, the adapted NOVA score performed well, suggesting that it could be useful in guiding clinical decisions.

Molecular imaging in Libman-Sacks endocarditis

Abstract We present a 54-year-old woman with systemic lupus erythematosus (SLE), fever, pericardial effusion and a mitral valve vegetation. 18F-Fluorodesoxyglucose positron emission tomography CT (18F-FDG-PET-CT) showed very high accumulation of the isotope at the mitral valve. The patient underwent cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, 18F-FDG-PET-CT clearly demonstrated the increased glucose uptake caused by infiltrating white blood cells in the ongoing inflammatory process at the mitral valve. In conclusion, 18F-FDG-PET-CT cannot be used to distinguish between IE and non-infective Libman-Sacks vegetations.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study

OBJECTIVESnIt is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization.nnnMETHODSnUsing Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group.nnnRESULTSnWe identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratiou2009=u20090.66 (95% confidence interval: 0.46-0.94) and hazard ratiou2009=u20090.59 (95% confidence interval: 0.37-0.96), respectively].nnnCONCLUSIONSnNo major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.

Correlation of iris biometrics and DNA

The presented work concerns prediction of complex human phenotypes from genotypes. We were interested in correlating iris color and texture with DNA. Our data consist of 212 eye images along with DNA: 32 single-nucleotide polymorphisms (SNPs). We used two types of biometrics to describe the eye images: One for iris color and one for iris texture. Both biometrics were high dimensional and a sparse principle component analysis (SPCA) reduced the dimensions and resulted in a representation of data with good interpretability. The correlations between the sparse principal components (SPCs) and the 32 SNPs were found using a canonical correlation analysis (CCA). The result was a single significant canonical correlation (CC) for both biometrics. Each CC comprised two correlated canonical variables, consisting of a linear combination of SPCs and a linear combination of SNPs, respectively. The significant canonical variables for color and texture were primarily explained by the first SPC (SPC1). Therefore, we made a visual inspection of the first SPCs. The color based SPC1 explained a blue to brown variation in iris color and the texture based SPC1 gave a general explanation of iris texture. The SNPs (rs12896399, rs3733542, rs6475555, rs12913832) and (rs12896399, rs3733542, rs12913832) had the highest correlation to the canonical variable for color and texture, respectively. Three of the most contributing SNPs were the same for both biometrics, revealing a covariance between iris color and texture.

Surface Detection Using Round Cut

We propose an iterative method for detecting closed surfaces in a volumetric data, where an optimal search is performed in a graph build upon a triangular mesh. Our approach is based on previous techniques for detecting an optimal terrain-like or tubular surface employing a regular grid. Unlike similar adaptations for triangle meshes, our method is capable of capturing complex geometries by iteratively refining the surface, where we obtain a high level of robustness by applying explicit mesh processing to intermediate results. Our method uses on-surface data support, but it also exploits data information about the region inside and outside the surface. This provides additional robustness to the algorithm. We demonstrate the capabilities of the approach by detecting surfaces of CT scanned objects.

Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia

The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex [CC]), and then evaluated the most significantly associated genes in a replication sample of 240 SAB cases (122 complicated and 118 uncomplicated, frequency matched for age, sex, and CC) using targeted sequence capture. In the discovery sample, gene-based analysis using the SKAT-O program identified 334 genes associated with complicated SAB at p<3.5 x 10−3. These, along with eight biologically relevant candidate genes were examined in the replication sample. Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated SAB (p = 1.2 x 10−4) after Bonferroni correction. In Firth-bias corrected logistic regression analysis of individual variants, the strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10−4). This variant is strongly correlated with a missense variant (rs2657879, p = 4.4 x 10−3) in which the minor allele (associated here with complicated SAB) has been previously associated with lower plasma concentration of glutamine. In a microarray-based gene-expression analysis, individuals with SAB exhibited significantly lower expression levels of GLS2 than healthy controls. Similarly, Gls2 expression is lower in response to S. aureus exposure in mouse RAW 264.7 macrophage cells. Compared to wild-type cells, RAW 264.7 cells with Gls2 silenced by CRISPR-Cas9 genome editing have decreased IL1-β transcription and increased nitric oxide production after S. aureus exposure. GLS2 is an interesting candidate gene for complicated SAB due to its role in regulating glutamine metabolism, a key factor in leukocyte activation.

Duration and complications of diabetes mellitus and the associated risk of infective endocarditis

BACKGROUNDnLong duration of diabetes mellitus (DM) is associated with an increased risk of infection, however no studies have yet focused on the duration of DM and the associated risk of infective endocarditis (IE).nnnMETHODSnPatients with DM were identified through the Danish Prescription Registry, 1996-2015. Duration of DM was split in follow-up periods of: 0-5u202fyears, 5-10u202fyears, 10-15u202fyears, and >15u202fyears. Multivariable adjusted Poisson regression was used to calculate incidence rate ratios (IRR) according to study groups. DM late-stage complications and the associated risk of IE were investigated as time-varying covariates using the validated Diabetes Complications Severity Index (DCSI).nnnRESULTSnWe included 299,551 patients with DM. In patients with DM duration of 0-5u202fyears, 5-10u202fyears, 10-15u202fyears, and >15u202fyears, the incidence rates of IE were 0.24, 0.33, 0.58, and 0.96 cases of IE/1000 person years, respectively. Patients with DM duration 5-10u202fyears, 10-15u202fyears, and >15u202fyears were associated with a higher risk of IE with an IRR of 1.24 (95% CI: 1.02-1.51), 1.92 (95% CI: 1.52-2.43) and 3.05 (95% CI: 2.11-4.40), respectively, compared with DM duration 0-5u202fyears. Patients with a DCSI score of 2, 3 and >3 were associated with a higher risk of IE compared with patients with a DCSI score of 0, IRRu202f=u202f1.78 (95% CI: 1.34-2.36), IRRu202f=u202f2.34 (95% CI: 1.73-3.16), and IRRu202f=u202f2.59 (95% CI: 1.92-3.48), respectively.nnnCONCLUSIONnThis study shows a stepwise increase in the risk of IE with DM duration and severity independent of age and known comorbidity.