| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Nygren, David, et al.
(författare)
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Low Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients
- 2022
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Ingår i: International Journal of General Medicine. - : Dove Medical Press Ltd. - 1178-7074. ; 15, s. 5843-5848
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Alpha- 1-antitrypsin (AAT) has been shown to inhibit SARS-CoV-2 cell entry and suggested as a therapeutic agent for COVID-19. Furthermore, epidemiological association of high prevalence of Alpha- 1-antitrypsin deficiency (AATD) and regional severity of COVID-19-impact has been hypothesized. In our study setting, the estimated prevalence rates of mild (PI*MZ, PI*SS or PI*MS) and moderate-to-severe AATD (PI*ZZ or PI*SZ) are high, 9% and 0.2%, respectively. Our primary aim was to examine the prevalence rate of AATD among hospitalized COVID-19-patients. Methods: In this prospective observational study, enrollment occurred from December 2020 to January 2021 in two COVID-19-units at Skane University Hospital, Lund, Sweden. Case definition was a patient hospitalized due to COVID-19. Patients were screened for AATD with PI-typing and if results were inconclusive, PCR for the S- and Z-genes were performed. Patients were categorized as severe or moderate COVID-19 and 30-day-mortality data were collected. The primary outcome was prevalence rate of AATD. The secondary outcome investigated association between presence of mild AATD and severe COVID-19. Results: We enrolled 61 patients with COVID-19. Two patients out of 61 (3%) had mild AATD (PI*MZ) and none had moderate-tosevere AATD. 30/61 (49%) had severe COVID-19. Both patients with mild AATD developed severe COVID-19. Yet, presence of AATD was not significantly associated with severe COVID-19 (p=0.24). Conclusion: Mild AATD (PI*MS or PI*MZ) was rare in a small cohort of hospitalized patients with COVID-19 in a study setting with a high background prevalence of AATD.
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| 3. |
- Ahlström, Gerd, et al.
(författare)
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Similarities and differences between China and Sweden regarding the core features of palliative care for people aged 60 or older : a systematic scoping review
- 2022
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Ingår i: BMC Palliative Care. - : Springer Science and Business Media LLC. - 1472-684X. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the increasing longevity of the world's population, with an unprecedented rise in the number of people who need palliative care (PC), there has been sparse research regarding palliative care for older people, especially when it comes to comparison of PC between healthcare systems and cultures. The aim of this systematic scoping review was to identify the characteristics of the body of literature and to examine the knowledge gaps concerning PC research for older people (> 60 years) in two healthcare systems and cultures, mainland China and Sweden.METHODS: The guidelines PRISMA (Preferred Reporting Items for Systematic Reviews), and PICOS (Patient/population, Intervention, Comparison/control, and Outcome) were used. Empirical studies on patients 60 years or older, next of kin or staff participating in a palliative care intervention or setting were included. They were conducted in mainland China or in Sweden during 2007-2019, were published in English and were extracted from seven databases: Embase, PubMed, Scopus, Cinahl, PsycInfo, Academic Search Complete and Cochrane Library. Two independent researchers conducted the selection of studies, data extraction and methodological evaluation. Any disagreements were resolved in consultation with a third researcher. The analysis was manifest directed content analysis based on PICOS domains.RESULTS: Of the 15 studies, four were from mainland China and 11 from Sweden. Both countries included older patients with cancer but also other end-stage diseases such as heart failure and dementia. The studies differed in design, method and the content of the interventions. The study in China based on traditional Chinese medicine concerns traditional Chinese folk music. The six qualitative studies from Sweden were evaluations of five interventions.CONCLUSIONS: Despite the high age of the participating patients, there was no focus on an ageing perspective concerning palliative care. To adapt to the changes taking place in most societies, future research should have increased focus on older persons' need for palliative care and should take account of issues concerning research ethics, ethnicity and culture.REGISTERED IN PROSPERO: CRD42020078685 , available from.
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| 4. |
- Aldén, Markus, et al.
(författare)
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Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3045. ; 44:3, s. 1115-1126
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and in-tegrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.
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| 5. |
- Aldman, Malin Hagstrand, et al.
(författare)
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Endocarditis due to Staphylococcus lugdunensis-a retrospective national registry-based study
- 2021
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 40, s. 1103-1106
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Tidskriftsartikel (refereegranskat)abstract
- We present characteristics of infective endocarditis (IE) caused by Staphylococcus lugdunensis and compare with IE caused by Staphylococcus aureus and other CoNS, in the National Swedish Registry of IE (2008-2018). Thirty episodes of S. lugdunensis IE were registered, of which 21 cases affected native valves, and 7 patients were subjected to surgery. The mortality rate at 30 days was significantly higher for S. lugdunensis IE (20%, n = 6), than for IE caused by other CoNS (7%) or S. aureus (9%) p = 0.016. Septic embolisation was only reported in two cases (7%). The most common treatment was isoxazolyl penicillin (n = 18).
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| 6. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 7. |
- Bahnan, Wael, et al.
(författare)
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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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| 8. |
- Berge, Andreas, et al.
(författare)
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Enterococcus faecalis bacteremia, cardiac implantable electronic device, extraction, and the risk of recurrence
- 2022
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Ingår i: Infection. - : Springer Science and Business Media LLC. - 0300-8126 .- 1439-0973. ; 50:6, s. 1517-1523
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In all patients with cardiac implantable electronic devices (CIED) and Enterococcus faecalis bacteremia (EfsB), endocarditis (IE) and CIED infection should be suspected. Guidelines recommend extraction of the CIED when CIED infection or IE is diagnosed. Whether extraction of the CIED should be done in other situations with EfsB is not known. We aimed to describe the management and outcome of patients with CIED and monomicrobial EfsB, in relation to extraction and recurrent EfsB. Methods: A population-based cohort of patients with monomicrobial EfsB from January 2014 to November 2020 was identified through microbiology registers in the Region Skåne, Sweden. Data on CIED and other clinical features were collected from medical records. Results: Among 1087 episodes of EfsB, 72 patients with CIED and monomicrobial EfsB were identified. Five of these patients were diagnosed with IE (7%), three of whom had echocardiographic changes on the CIED. Four CIED were extracted (6%). Recurrences were found in seven of 68 patients (10%) not subjected to extraction and in none of the extracted. In the group of patients without extraction, community acquisition and predisposition for IE were significantly associated with recurrent infection in univariate analyses. No infections involving the CIED were diagnosed during the recurrences. Conclusions: In patient with monomicrobial EfsB, it seems safe to omit extraction if no structural changes are found on the CIED.
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| 9. |
- Berge, Andreas, et al.
(författare)
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Epidemiology, bacteriology, and clinical characteristics of HACEK bacteremia and endocarditis : a population-based retrospective study
- 2020
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373.
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to describe the epidemiology, bacteriology, clinical presentation, risk factors for endocarditis (IE), diagnostic workup, and outcome of patients with bacteremia caused by the non-influenzae Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella genera (HACEK). A retrospective population-based cohort of patients with bacteremia collected from 2012 to 2017 was identified. Clinical data from identified patients were collected from medical records to classify patients, calculate incidences, analyze risk factors of IE, and describe the management and outcome of the cohort. A total of 118 episodes of HACEK bacteremia were identified, of which 27 were definite IE. The incidence of HACEK bacteremia was 5.2 and of HACEK IE 1.2 episodes per 1,000,000 inhabitants per year. Other focal infections were identified in 55 of 118 of the episodes, most commonly within the abdomen (26 episodes). The propensity to cause IE ranged from 62 in Aggregatibacter actinomycetemcomitans to 6% in Eikenella. Risk factors for IE were cardiac implantable electronical device, predisposing cardiac conditions, community acquisition, long duration of symptoms, multiple positive blood cultures, fever, heart murmur, embolization, and unknown origin of infection. The scoring system DENOVA developed to predict IE in bacteremia with Enterococcus faecalis also had a high sensitivity and specificity for predicting IE in HACEK bacteremia. The 30-day mortality was 4% in IE and 15% in non-IE bacteremia, and only one case of relapse was found. IE is common in bacteremia with Aggregatibacter, Cardiobacterium, and Kingella but relatively rare in Haemophilus and Eikenella. Treatment failures are very rare, and DENOVA can be used to evaluate the need for transesophageal echocardiography.
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| 10. |
- Berge, Andreas, et al.
(författare)
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S taphylococcus aureus bacteraemia, cardiac implantable electronic device, and the risk of endocarditis : a retrospective population–based cohort study
- 2023
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 42:5, s. 583-591
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having infective endocarditis (IE). The objectives were to describe a Swedish population-based cohort of patients with CIED and SAB, to identify risk factors, and to construct a predictive score for IE. Patients over 18 years old in the Stockholm Region identified to have SAB in the Karolinska Laboratory database from January 2015 through December 2019 were matched to the Swedish Pacemaker and Implantable Cardioverter-Defibrillator ICD Registry to identify the study cohort. Data were collected from study of medical records. A cohort of 274 patients with CIED and SAB was identified and in 38 episodes (14%) IE were diagnosed, 19 with changes on the CIED, and 35 with changes on the left side of the heart. The risk factors predisposition for IE, community acquisition, embolization, time to positivity of blood cultures, and growth in blood culture after start of therapy in blood cultures were independently associated to IE. A score to identify patients with IE was constructed, the CTEPP score, and the chosen cut-off generated a sensitivity of 97%, specificity of 25%, and a negative predictive value of 98%. The score was externally validated in a population-based cohort of patients with CIED and SAB from another Swedish region. We found that 14% of patients with CIED and SAB had definite IE diagnosed. The CTEPP-score can be used to predict the risk of IE and, when negative, the risk is negligible.
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