| 1. |
- Iversen, Søren, et al.
(författare)
-
Alteration of Bacterial Communities in Anterior Nares and Skin Sites of Patients Undergoing Arthroplasty Surgery : Analysis by 16S rRNA and Staphylococcal-Specific tuf Gene Sequencing
- 2020
-
Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n = 83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p = 0.04) and staphylococcal (p = 0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p = 0.001) abundance and Staphylococcus hominis (p = 0.01) relative staphylococcal abundance. In nares, significant reductions occurred for Staphylococcus hominis (p = 0.02), Staphylococcus haemolyticus (p = 0.02), and Staphylococcus pasteuri (p = 0.003) relative to other staphylococci. Staphylococcus aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. Staphylococcus epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.
|
|
| 2. |
- Månsson, Emeli, 1978-, et al.
(författare)
-
Comparative genomics of Staphylococcus epidermidis from prosthetic : from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence
- 2021
-
Ingår i: Microbial Genomics. - London, United Kingdom : Society for General Microbiology. - 2057-5858. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- There is increased awareness of the worldwide spread of specific epidemic multidrug-resistant (MDR) lineages of the human commensal Staphylococcus epidermidis. Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and k-mers) that distinguish S. epidermidis causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from S. epidermidis from PJIs prospectively collected over 10 years in Sweden, and contemporary S. epidermidis from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated. Publicly available S. epidermidis sequences were used for international extrapolation and validation of findings. Our data show that S. epidermidis causing PJIs differed from nasal isolates not by virulence but by traits associated with resistance to compounds used in prevention of PJIs: β-lactams, aminoglycosides and chlorhexidine. Almost a quarter of the PJI isolates did not belong to any of the previously described major nosocomial lineages, but the AMR-related traits were also over-represented in these isolates, as well as in international S. epidermidis isolates originating from PJIs. Genes previously associated with virulence in S. epidermidis were over-represented in individual lineages, but failed to reach statistical significance when adjusted for population structure. Our findings suggest that the current strategies for prevention of PJIs select for nosocomial MDR S. epidermidis lineages that have arisen from horizontal gene transfer of AMR-related traits into multiple genetic backgrounds.
|
|
| 3. |
|
|
| 4. |
- Månsson, Emeli, 1978-, et al.
(författare)
-
Methicillin-Resistant Staphylococcus epidermidis Lineages in the Nasal and Skin Microbiota of Patients Planned for Arthroplasty Surgery
- 2021
-
Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus epidermidis, ubiquitous in the human nasal and skin microbiota, is a common causative microorganism in prosthetic joint infections (PJIs). A high proportion of PJI isolates have been shown to harbor genetic traits associated with resistance to/tolerance of agents used for antimicrobial prophylaxis in joint arthroplasties. These traits were found within multidrug-resistant S. epidermidis (MDRSE) lineages of multiple genetic backgrounds. In this study, the aim was to study whether MDRSE lineages previously associated with PJIs are present in the nasal and skin microbiota of patients planned for arthroplasty surgery but before hospitalization. We cultured samples from nares, inguinal creases, and skin over the hip or knee (dependent on the planned procedure) taken two weeks (median) prior to admittance to the hospital for total joint arthroplasty from 66 patients on agar plates selecting for methicillin resistance. S. epidermidis colonies were identified and tested for the presence of mecA. Methicillin-resistant S. epidermidis (MRSE) were characterized by Illumina-based whole-genome sequencing. Using this method, we found that 30/66 (45%) of patients were colonized with MRSE at 1-3 body sites. A subset of patients, 10/66 (15%), were colonized with MDRSE lineages associated with PJIs. The qacA gene was identified in MRSE isolates from 19/30 (63%) of MRSE colonized patients, whereas genes associated with aminoglycoside resistance were less common, found in 11/30 (37%). We found that MDRSE lineages previously associated with PJIs were present in a subset of patients' pre-admission microbiota, plausibly in low relative abundance, and may be selected for by the current prophylaxis regimen comprising whole-body cleansing with chlorhexidine-gluconate containing soap. To further lower the rate of S. epidermidis PJIs, the current prophylaxis may need to be modified, but it is important for possible perioperative MDRSE transmission events and specific risk factors for MDRSE PJIs to be investigated before reevaluating antimicrobial prophylaxis.
|
|
| 5. |
- Petersen, Tanja Gram, et al.
(författare)
-
Ten-year follow-up of fracture risk in a systematic population-based screening program : the risk-stratified osteoporosis strategy evaluation (ROSE) randomised trial
- 2024
-
Ingår i: EClinicalMedicine. - 2589-5370. ; 71
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program. Methods: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65–80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed. Findings: All randomised women were included February 4, 2010–January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality. Interpretation: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake. Funding: INTERREG and the Region of Southern Denmark.
|
|
| 6. |
- Pingel, Jessica, et al.
(författare)
-
Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
|
|
| 7. |
- Rendboe, Amalie Katrine, et al.
(författare)
-
The Epidome : a species-specific approach to assess the population structure and heterogeneity of Staphylococcus epidermidis colonization and infection
- 2020
-
Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough generally known as a human commensal, Staphylococcus epidermidis is also an opportunistic pathogen that can cause nosocomial infections related to foreign body materials and immunocompromized patients. Infections are often caused by multidrug-resistant (MDR) lineages that are difficult and costly to treat, and can have a major adverse impact on patients’ quality of life. Heterogeneity is a common phenomenon in both carriage and infection, but present methodology for detection of this is laborious or expensive.In this study, we present a culture-independent method, labelled Epidome, based on an amplicon sequencing-approach to deliver information beyond species level on primary samples and to elucidate clonality, population structure and temporal stability or niche selection of S. epidermidis communities.ResultsBased on an assessment of > 800 genes from the S. epidermidis core genome, we identified genes with variable regions, which in combination facilitated the differentiation of phylogenetic clusters observed in silico, and allowed classification down to lineage level. A duplex PCR, combined with an amplicon sequencing protocol, and a downstream analysis pipeline were designed to provide subspecies information from primary samples. Additionally, a probe-based qPCR was designed to provide valuable absolute abundance quantification of S. epidermidis. The approach was validated on isolates representing skin commensals and on genomic mock communities with a sensitivity of < 10 copies/μL. The method was furthermore applied to a sample set of primary skin and nasal samples, revealing a high degree of heterogeneity in the S. epidermidis populations. Additionally, the qPCR showed a high degree of variation in absolute abundance of S. epidermidis.ConclusionsThe Epidome method is designed for use on primary samples to obtain important information on S. epidermidis abundance and diversity beyond species-level to answer questions regarding the emergence and dissemination of nosocomial lineages, investigating clonality of S. epidermidis communities, population dynamics, and niche selection. Our targeted-sequencing method allows rapid differentiation and identification of clinically important nosocomial lineages in low-biomass samples such as skin samples.
|
|
| 8. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 9. |
- Strøm, Michael, et al.
(författare)
-
Assessment of EVAR Competence : Validity of a Novel Rating Scale (EVARATE) in a Simulated Setting
- 2018
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 56:1, s. 137-144
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims of this study were to investigate the validity evidence for a novel procedure specific assessment tool of competence in endovascular aortic repair (EVAR) and to establish a pass/fail level for the assessment. Methods: Computed tomography angiography data of a 55 mm in diameter infrarenal aortic aneurysm was implemented into an endovascular simulator. Twenty-three physicians with varying EVAR experiences were video-recorded when performing a standard EVAR procedure on the simulator. Two experienced EVAR operators assessed the participants using the novel rating scale, “EndoVascular Aortic Repair Assessment of Technical Expertise” (EVARATE). Validity was studied according to the framework endorsed by the American Educational Research Association. Results: The EVARATE scale had a high internal consistency (Cronbach's alpha =.90). The inter-rater reliability was acceptable (Intraclass Correlation Coefficient =.68, p =.005). Specific EVAR experience correlated significantly with the EVARATE score (Spearman's rho =.62, p =.002), but general endovascular experience did not. Consequence analysis showed that the EVARATE assessment could distinguish novices from intermediates (p <.01) and from experts (p <.001). A pass/fail score was determined using the contrasting groups’ method. Conclusion: This paper presents the initial validity evidence for a novel procedure specific assessment tool, EVARATE, for operator competence in endovascular aortic repair investigated in a simulated setting. The assessment tool can be used to provide structured formative feedback to trainees.
|
|
| 10. |
|
|
