| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 5. |
- Wood, Hannah L., 1980, et al.
(författare)
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The effect of environmental stressors on the early development of the Norway lobster Nephrops norvegicus (L.).
- 2015
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Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 473, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- The marine environment is changing and becoming less stable as a result of direct (e.g. lower pH) and indirect (e.g. salinity fluctuations from changing rainfall) effects of climate change. The larval stages may be a bottleneck for reproductive success and recruitment, therefore the potential for environmental stressors to impact upon larval recruitment is high; the ability to tolerate environmental stress in early life history is crucial to an individual's overall fitness. This study investigated the effect of hypercapnia and salinity stress on the early life stages of the Norway Lobster Nephrops norvegicus. Sensitivity to hypercapnia was shown to be highly brood specific with large differences in mortality between broods under hypercapnic stress. Furthermore, this environmental stressor was demonstrated to increase the energetic demand on the larvae, which could potentially have a negative effect later in development. Salinity stress experiments were not designed to test brood specific effects but did demonstrate increased energy usage (higher MR and lower weight) under salinity stress. Although the larvae were tolerant to present levels of salinity stress future changes in this stressor may alter species distribution. This study demonstrated that environmental stressors have the potential to have a large effect on future recruitment. Further, future studies need to consider mechanisms that affect an individual's tolerance from conception, such as epigenetics, maternal provisioning and genetic factors, to determine what makes some individuals tolerant where others are not.
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| 6. |
- Eriksson, Hannah K., et al.
(författare)
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Does the Alpha-defensin Immunoassay or the Lateral Flow Test Have Better Diagnostic Value for Periprosthetic Joint Infection? : A Systematic Review
- 2018
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 476:5, s. 1065-1072
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Forskningsöversikt (refereegranskat)abstract
- Background: Measuring alpha-defensin concentrations in synovial fluid may help to diagnose periprosthetic joint infection (PJI). There are two commercially available methods for measuring alpha-defensin in synovial fluid: the enzyme-linked immunosorbent assay-based Synovasure (R) alpha-defensin immunoassay, which gives a numeric readout within 24 hours, and the Synovasure lateral flow test, which gives a binary readout within 20 minutes. There is no compilation of the existing literature to support the use of one of these two tests over the other.Questions/purposes: Does the immunoassay or the lateral flow test have better diagnostic value (sensitivity and specificity) in diagnosing PJI?Methods: We followed PRISMA guidelines and identified all studies on alpha-defensin concentration in synovial fluid as a PJI diagnostic marker, indexed to April 14, 2017, in PubMed, JSTOR, Google Scholar, and OVID databases. The search retrieved 1578 records. All prospective and retrospective studies on alpha-defensin as a PJI marker (PJI classified according to the criteria of the Musculoskeletal Infection Society) after THA or TKA were included in the analysis. All studies used only one of the two commercially available test methods, but none of them was comparative. After excluding studies with overlapping patient populations, four studies investigating the alpha-defensin immunoassay and three investigating the lateral flow test remained. Alpha-defensin immunoassay studies included 482 joints and lateral flow test studies included 119. The quality of the trials was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The heterogeneity among studies was evaluated by the I-2 index, indicating that the heterogeneity of the included studies was low. Pooled sensitivity, specificity, positive and negative likelihood ratios, and receiver operating curves were calculated for each method and compared with each other.Results: The alpha-defensin immunoassay had superior overall diagnostic value compared with the lateral flow test (area under the curve, 0.98 versus 0.75) with higher sensitivity (96% [90%-98%] versus 71% [55%-83%], p < 0.001), but no difference in specificity with the numbers available (96% [93%-97%] versus 90% [81%-95%], p = 0.060).Conclusions: Measurement of alpha-defensin in synovial fluid is a valuable complement to existing diagnostic criteria, and the immunoassay test detects PJI more accurately than the lateral flow test. The lateral flow test has lower sensitivity, making it difficult to rule out infection, but its relatively high specificity combined with the advantage of a quick response time can make it useful to rule in infection perioperatively.Level of Evidence: Level III, diagnostic study.
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| 7. |
- Eriksson, Hannah K., MD, et al.
(författare)
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Early Staphylococcal Periprosthetic joint infection (PJI) caused by Staphylocci resistant to rifampicin : Inferior outcomes after Debridement, Antibiotics and Implant retention (DAIR)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The purpose of this retrospective cohort study was to investigate whether rifampicin resistance in early periprosthetic joint infection (PJI) caused by Staphylococci (Coagulase negative staphylococci (CoNS) or Staphyloccocus aureus (SA)) affects the treatment outcome after debridement, antibiotics and implant retention (DAIR).Patients and methods: 81 patients (42 women) with a mean age of 72 (41-93) years affected by early PJI (30 knees, 51 hips) were included. Early PJI was defined as infection diagnosed within 6 weeks after the index surgical procedure, where index procedures could be either primary or revision surgeries. The diagnosis of PJI was based on MSIS (Musculoskeletal Infection Society) criteria and all patients were treated surgically by DAIR, repeated if needed. Infection-free survival was estimated using the Kaplan Meier method, and Cox regression models were fitted to assess the risk of unsuccessful treatment outcome, adjusted for the potential confounders sex, joint (hip or knee), type of index surgery (primary or revision) and age (dichotomised into age ˂ 70 or ≥ 70). Outcome measures: The primary endpoint was to compare treatment outcome in patients with PJI caused by rifampicin-resistant or rifampicin-sensitive Staphylococci after one DAIR procedure and secondary endpoint to compare outcome after two DAIR procedures. Results: The treatment was unsuccessful in 58% of patients after one DAIR procedure and in 42% after two DAIR procedures. In the group of patients with rifampicin-resistant Staphylococci, treatment was unsuccessful in 80% after one DAIR and 70% after two DAIR procedures. In patients with rifampicin-sensitive bacteria, 49% of the patients had an unsuccessful treatment after one DAIR and 33% after two DAIR. Patients with rifampicin-resistant staphylococcal PJI had a risk of infection relapse of 1.9 (95% CI: 1.1-3.6, p=0.04) after one DAIR when compared with patients with rifampicin-sensitive bacteria, and a 4.1 (95% CI: 1.2-14.1, p=0.03) -fold risk of treatment failure after two DAIR procedures.Conclusion: Staphylococcal resistance to rifampicin is associated with inferior outcomes in early PJI treated by DAIR. These findings are suggestive of a change in practice since DAIR may not be a useful strategy under these circumstances.
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| 8. |
- Eriksson, Hannah K., MD, et al.
(författare)
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Early Staphylococcal Periprosthetic Joint Infection (PJI) Treated with Debridement, Antibiotics, and Implant Retention (DAIR) : Inferior Outcomes in Patients with Staphylococci Resistant to Rifampicin
- 2023
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Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown how rifampicin resistance in staphylococci causing a periprosthetic joint infection (PJI) affects outcomes after debridement, antibiotics, and implant retention (DAIR). We thus aimed to compare the risk of relapse in DAIR-treated early PJI caused by staphylococci with or without rifampicin resistance. In total, 81 patients affected by early PJI were included, and all patients were treated surgically with DAIR. This was repeated if needed. The endpoint of relapse-free survival was estimated using the Kaplan–Meier method, and Cox regression models were fitted to assess the risk of infection relapse for patients infected with rifampicin-resistant bacteria, adjusted for age, sex, type of joint, and type of index surgery. In patients with rifampicin-resistant staphylococci, relapse was seen in 80% after one DAIR procedure and in 70% after two DAIR procedures. In patients with rifampicin-sensitive bacteria, 51% had an infection relapse after one DAIR procedure and 33% had an infection relapse after two DAIR procedures. Patients with rifampicin-resistant staphylococcal PJI thus had an increased adjusted risk of infection relapse of 1.9 (95% CI: 1.1–3.6, p = 0.04) after one DAIR procedure compared to patients with rifampicin-sensitive bacteria and a 4.1-fold (95% CI: 1.2–14.1, p = 0.03) increase in risk of infection relapse after two DAIR procedures. Staphylococcal resistance to rifampicin is associated with inferior outcomes after DAIR. These findings suggest that DAIR may not be a useful strategy in early PJI caused by rifampicin-resistant staphylococci.
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| 9. |
- Eriksson, Hannah K., et al.
(författare)
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Linezolid in the treatment of periprosthetic joint infection caused by coagulase-negative staphylococci
- 2019
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Ingår i: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:9, s. 683-690
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Tidskriftsartikel (refereegranskat)abstract
- Background: Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CoNS) is increasingly common and is sometimes treated with off-label use of linezolid.Methods: We conducted a retrospective study of patients with PJI caused by CoNS treated with surgical intervention and orally administrated linezolid during the period 1995-2014 (n = 28). Clinical outcomes and adverse events related to linezolid administration were evaluated. Mean time to follow-up was 4.3 years (range: 0.2-12).Results: Twenty-two of 28 patients were infection-free at follow-up. No CoNS strain was resistant to vancomycin, but 16 of 28 were resistant to rifampicin, 23 of 28 to clindamycin and 20 of 27 to quinolones. The mean duration of linezolid treatment was 4.2 weeks (range: 1-12). Eleven of 28 patients had an adverse event related to the antimicrobial treatment, and four had to discontinue linezolid, but all adverse events were reversible within 2 months after discontinuation.Conclusions: Oral linezolid administration combined with adequate surgical treatment may be useful for the treatment of PJIs caused by CoNS.
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| 10. |
- Eriksson, Hannah K., MD, et al.
(författare)
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Low accuracy in preoperative tissue biopsies for diagnosing chronic periprosthetic joint infection : an observational retrospective single-centre study
- 2023
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Ingår i: Journal of international medical research. - : Sage Publications. - 0300-0605 .- 1473-2300. ; 51:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective Diagnosing periprosthetic joint infection (PJI) can be challenging. The ability to distinguish between septic and aseptic failure of a joint prosthesis is crucial for treatment strategy optimisation and prognosis prediction. Preoperative tissue cultures are included in many diagnostic algorithms; however, studies report different degrees of concordance (63%-85%) with intraoperative cultures. This study aimed to investigate the diagnostic performance of tissue biopsies in the preoperative diagnostic process with the 2018 International Consensus Meeting criteria as a reference and to describe the concordance between microbiological findings in pre- and intraoperative biopsies.Methods This observational retrospective study included 44 patients requiring revision surgery of a total hip or knee arthroplasty, where the diagnostic workup included biopsies of periprosthetic tissue. The accuracy of preoperative biopsies was calculated, and concordance between microbiological findings in pre- and intraoperative biopsies was described.Results The accuracy was 59%, with a sensitivity of 50% and specificity of 79%. Full concordance between microbiological findings in pre- and intraoperative biopsies was found in 64% of the cases.Conclusion An open biopsy of periprosthetic tissue cannot reliably confirm or exclude PJI, and, therefore, should not be performed.
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