Retrospective analysis of 291 cases of Staphylococcus aureus bacteraemia (SAB) from 06/2017 to 06/2019 at the University Hospital of Leipzig, Germany: Investigation of adherence to the SAB care bundle, effects on mortality, clinical outcomes, and characterization of strains

From June 2017 to June 2019, 291 cases of Staphylococcus aureus bacteraemia (SAB) were evaluated retrospectively. Patient baseline characteristics, clinical presentations, empiric and targeted treatment, and clinical outcomes were assessed. Our study aimed to evaluate the adherence to a designated SAB care bundle and to assess whether proper adherence improved patient survival. Furthermore, as data for spa type distributions in MSSA-SAB are scarce for Germany, we aimed to describe circulating spa types and spa Clonal Complexes (spa CC) in our epidemiological setting

Phylogenetic relationships of species of Raymunida (Decapoda: Galatheidae) based on morphology and mitochondrial cytochrome oxidase sequences, with the recognition of four new species

19 pages.-- RECEIVED: 10 April 2000, ACCEPTED: 8 November 2000.The species of the genus Raymunida from the Pacific and Indian oceans are revised using morphological characters and the mitochondrial cytochrome oxidase subunit I sequences. Four new species are described (R. confundens, R. dextralis, R. erythrina, and R. insulata), and the status of R. bellior and R. elegantissima are revised. The species of Raymunida can be identified by subtle morphological characters, which match differences in mitochondrial nucleotide sequences. Therefore, the sequence divergences confirm the specific and phylogenetic value of some morphological characters (e.g., length of the mesial spine on the basal antennal segment, length of the walking legs). Furthermore, they confirm the importance of the color pattern as a diagnostic character. The widespread species (R. elegantissima), known from the Philippines to Fiji, shows minimal divergence between specimens from different localities (maximum of 3 nucleotide differences or 0.2% mean divergence). The phylogenetic reconstruction agreed with the monophyletic condition of Raymunida and its differentiation with respect to the genus Munida (in which Raymunida species had previously been included) and Agononida.Peer reviewe

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer’s disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed “practice effects”). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies

New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis

Aims: In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. Material and methods: Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). Results: Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. Conclusion: The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes

Retrospective analysis of 291 cases of Staphylococcus aureus bacteraemia (SAB) from 06/2017 to 06/2019 at the University Hospital of Leipzig, Germany: Investigation of adherence to the SAB care bundle, effects on mortality, clinical outcomes, and characterization of strains

From June 2017 to June 2019, 291 cases of Staphylococcus aureus bacteraemia (SAB) were evaluated retrospectively. Patient baseline characteristics, clinical presentations, empiric and targeted treatment, and clinical outcomes were assessed. Our study aimed to evaluate the adherence to a designated SAB care bundle and to assess whether proper adherence improved patient survival. Furthermore, as data for spa type distributions in MSSA-SAB are scarce for Germany, we aimed to describe circulating spa types and spa Clonal Complexes (spa CC) in our epidemiological setting

Cognitive decline in Parkinson’s disease: the impact of the motor phenotype on cognition

Objectives Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings

Long-term cognitive decline related to the motor phenotype in parkinson’s disease

Background: Parkinson's disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Objective: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Methods: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M= 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year followup data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M= 66.10; 68.6% males). Results: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients was present and we found differences for motor phenotypes in attention (beta = -0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by -0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Conclusion: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype

Phenotype.

<p>Phenotype.</p

Surface analysis of infected valves.

<p>For surface analysis using scanning electron microscopy (SEM), infected native (A-C; patient 3) and prosthetic (D-F; patient 7) heart valve tissues were cut into small pieces and fixed. After pretreatment and exposure to osmium tetroxide, tissues were dehydrated and mounted on standard SEM stubs with carbon tape. The cured samples were finally sputter-coated with a platinum layer and evaluated with a scanning electron microscope. (A-C) SEM images of the surface of an infected native valve. (A) Overview. (B) Epithelial cell boundaries are discernable. Inset: note that few bacteria are attached to the smooth surface and that these seem to be often damaged (arrow). (C) At higher magnification scattered bacteria showing apparently intact morphology (arrow) can also be found. (D-F) Ultrastructure images of infected biological prosthetic valve. (D) Overview. (E) The surface is characterized by deep holes and cracks where microbes may be concealed; the surface appears rough. Inset: note that the few bacteria attached to the outside often seem to be damaged (arrow). (F) At higher magnification a number of apparently intact bacteria (arrows) showing different morphologies can be found; note the fibrous structure of the substrate, providing ideal adhesion sites.</p

Ultrastructural features of infective endocarditis.

<p>Using focused ion beam scanning electron microscopy (FIB-SEM), 3D reconstructions of infected phagocytic cells were generated. (A) Transversal cut through a native infected valve (patient 3). Cells cluttered with numerous viable bacteria showed evidence of a process of intracellular bacterial survival. Nuclei of human cells are indicated by n (black or white). Note some cells carrying a large number of bacteria that nearly fill the cytoplasmic space. Survival of these cells would be unlikely. Inset: a further example from another area. (B) Transverse cut through a biological prosthesis infected with <i>Staphylococcus aureus</i> (patient 5). Monocytes cluttered with numerous viable bacteria show evidence of a process in which bacteria escape from a phagocytic vacuole into the cytoplasm; the plasma membrane of some cells is partially disrupted (white arrows), indicating cell death and release of bacterial cargo. Nuclei of monocytes showing intact plasma membrane are indicated by n (black), and the nucleus of a heavily damaged immune cell is indicated by n (white); arrowheads denote phagosomes with intact (black) and disrupted membranes (white); white arrows indicate disrupted plasma membranes. Insets: further examples from another area. (C-E, patient 3) 3View-SEM 3D-reconstruction of a 11.2 μm x 13.3 μm x 3.2 μm (xyz) block at 10 nm x 10 nm x 50 nm (xyz) resolution showing two cells cluttered with numerous viable bacteria (yellow); yellow = bacteria, green = cell membrane. (F-H, patient 5) 3View-SEM 3D-reconstruction of a 24.6 μm x 19.2 μm x 5.7 μm (xyz) block at 10 nm x 10 nm x 50 nm (xyz) resolution showing a monocyte cluttered with numerous viable bacteria (yellow); note that the plasma membrane is partially disrupted (arrows), indicating death of the cell. In addition, several bacteria are located within the extracellular space (red); yellow = bacteria, green = cell membrane, blue = nucleus. (I-K, patient 5) High resolution (2.5 nm x 2.5 nm x 5 nm (xyz)); (F) the nucleus of the cell is highly fragmented as is typical for neutrophilic granulocytes.</p