{"entity": "researcher", "timestamp": "2026-06-15T17:46:16.652Z", "family": "Hailer", "given": "Nils P", "initials": "NP", "orcid": "0000-0002-3233-2638", "affiliations": ["Department of Surgical Sciences, Orthopaedics, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/4c8bb8c013184ef7b482ffe6f8f1380b.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/4c8bb8c013184ef7b482ffe6f8f1380b"}}, "publications": [{"entity": "publication", "iuid": "2c25ac8902974f2bad8f06180c49be2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c25ac8902974f2bad8f06180c49be2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c25ac8902974f2bad8f06180c49be2f"}}, "title": "Treatment of Periprosthetic Joint Infection with Intravenous Vancomycin: Do We Hit the Target?", "authors": [{"family": "Haglund", "given": "Rasmus", "initials": "R"}, {"family": "Tornberg", "given": "Ulrika", "initials": "U"}, {"family": "Claesson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Hailer", "given": "Nils P", "initials": "NP", "orcid": "0000-0002-3233-2638", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8bb8c013184ef7b482ffe6f8f1380b.json"}}], "type": "journal article", "published": "2024-12-18", "journal": {"title": "Antibiotics (Basel)", "issn": "2079-6382", "volume": "13", "issue": "12", "issn-l": null}, "abstract": "Background/objectives: Vancomycin is commonly used in the treatment of periprosthetic joint infection (PJI), and trough concentrations are measured to ascertain that they are within the therapeutic range. It has not been investigated what proportion of vancomycin concentrations during treatment of PJI patients is accurately within this range, how many dose adjustments are commonly needed, and which patient factors predispose towards aberrations from the desired range. Method: In this single-center cohort study, we investigated vancomycin trough concentrations in 108 patients with surgically treated PJI who received IV administered vancomycin treatment post-operatively. Patients were identified in our local arthroplasty register, and data beyond what was available in the register were collected from electronic medical charts. Results: Of the final study cohort, 41% were women, and the median age was 71 (IQR 63-79) years. Most patients had PJI of the hip (73%), the majority (54%) underwent a debridement, antibiotics and implant retention (DAIR) procedure prior to vancomycin treatment, and 39% received vancomycin-loaded bone cement during the preceding revision procedure. Of 791 vancomycin trough measurements, only 58.2% were within the target range of 15-20 mg/L, 18.5% were below, and 23.4% were above. A total of 71% of all patients required at least one dose adjustment, and the median length of vancomycin treatment was 8 days. We observed positive correlations of vancomycin trough concentrations with both age (Spearman's rho = 0.35, p < 0.001) and pre-treatment creatinine concentrations (Spearman's rho = 0.34, p < 0.001), but no statistically significant difference between patients who had received vancomycin-loaded bone cement and those who had not. Conclusions: In our PJI patients, a high proportion of vancomycin trough concentrations were outside the therapeutic range, despite adherence to local and national guidelines. We can also confirm that caution needs to be exerted in patients of advanced age and those with compromised kidney function. Alternative broad-spectrum antibiotics that do not require as extensive therapeutic drug monitoring should be further explored.", "doi": "10.3390/antibiotics13121226", "pmid": "39766617", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11727632"}, {"db": "pii", "key": "antibiotics13121226"}], "notes": [], "created": "2025-02-17T09:20:45.877Z", "modified": "2025-02-17T09:20:46.439Z"}, {"entity": "publication", "iuid": "866d56297cbc40a4b9f857305c123888", "links": {"self": {"href": "https://publications.scilifelab.se/publication/866d56297cbc40a4b9f857305c123888.json"}, "display": {"href": "https://publications.scilifelab.se/publication/866d56297cbc40a4b9f857305c123888"}}, "title": "Effects of denosumab treatment on the expression of receptor activator of nuclear kappa-B ligand (RANKL) and TNF-receptor TNFRSF9 after total hip arthroplasty-results from a randomized placebo-controlled clinical trial.", "authors": [{"family": "Sk\u00f6ld", "given": "C", "initials": "C", "orcid": "0000-0002-2583-5448", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6b2783b9b194e66886445cbafe37bb8.json"}}, {"family": "Kultima", "given": "K", "initials": "K", "orcid": "0000-0002-0680-1410", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ae376585168459681f5e2cae0c75b96.json"}}, {"family": "Freyhult", "given": "E", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Larsson", "given": "A", "initials": "A", "orcid": "0000-0003-3161-0402", "researcher": {"href": "https://publications.scilifelab.se/researcher/2276de26382b402aa384ac231f30f156.json"}}, {"family": "Gordh", "given": "T", "initials": "T", "orcid": "0000-0003-1454-3148", "researcher": {"href": "https://publications.scilifelab.se/researcher/de40b19a854f4dda88986d2e00e8f091.json"}}, {"family": "Hailer", "given": "N P", "initials": "NP", "orcid": "0000-0002-3233-2638", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8bb8c013184ef7b482ffe6f8f1380b.json"}}, {"family": "Mallmin", "given": "H", "initials": "H", "orcid": "0000-0002-0074-7484", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb14dfd7144c4a06970d45cbbdc0e97d.json"}}], "type": "journal article", "published": "2022-09-00", "journal": {"title": "Osteoporos Int", "issn": "1433-2965", "volume": "33", "issue": "9", "pages": "1-8", "issn-l": "0937-941X"}, "abstract": "We investigated whether the drug denosumab modulates the inflammatory response after total hip arthroplasty in a randomized controlled trial. Significantly increased expression of RANKL was found in patients treated with denosumab. This could provide an explanation for the rebound effect with rapid loss of BMD seen after discontinuation of denosumab treatment.\n\nTo evaluate whether denosumab, a human monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand (RANKL), modulates the inflammatory response after cementless total hip arthroplasty (THA) in patients with osteoarthritis of the hip.\n\nSixty-four patients operated with cementless THA were randomized to two doses of 60-mg denosumab or placebo 1-3 days and 6 months postoperatively. Serum samples were analyzed by a multiplex extension assay detecting 92 inflammation-related proteins. Bone turnover markers were assessed. Proteins were analyzed using linear mixed effect models. Validation of conspicuous findings was performed with ELISA.\n\nTwo proteins were significantly affected by denosumab treatment: RANKL and tumor necrosis factor receptor super family member 9 (TNFRSF9). Serum levels of RANKL were more than twice as high in the denosumab than in the placebo group 3 months after surgery (ratio 2.10, p<0.001). Six and 12 months after surgery, the expression of RANKL was still elevated in the denosumab-treated group (ratios 1.50, p < 0.001; 1.47, p =0.002). The expression of TNFRSF9 was lower in the denosumab group at 3 months (ratio 0.68, p<0.001). In the denosumab group, concentrations of bone turnover markers were substantially reduced after 3 months, remained suppressed after 6 and 12 months, but increased above baseline at 24 months after surgery.\n\nTwo subcutaneous denosumab injections 6 months apart increase RANKL and depress TNFRSF9 after THA. This provides a possible explanation for the rebound effect on bone turnover markers as well as bone mineral density (BMD) upon withdrawal of denosumab. None of the other measured markers of inflammation was influenced by denosumab treatment.", "doi": "10.1007/s00198-022-06423-w", "pmid": "35608639", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9463208"}, {"db": "pii", "key": "10.1007/s00198-022-06423-w"}], "notes": [], "created": "2022-12-02T08:48:20.134Z", "modified": "2022-12-02T08:48:20.308Z"}, {"entity": "publication", "iuid": "dab2208caeea405eac67dbba14f79339", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dab2208caeea405eac67dbba14f79339.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dab2208caeea405eac67dbba14f79339"}}, "title": "Risk of Revision After Arthroplasty Associated with Specific Gene Loci: A Genomewide Association Study of Single-Nucleotide Polymorphisms in 1,130 Twins Treated with Arthroplasty.", "authors": [{"family": "Br\u00fcggemann", "given": "Anders", "initials": "A", "orcid": "0000-0002-3600-253", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbd0a479f8464bc6b309e1ecd9b7a9ea.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Micha\u00eblsson", "given": "Karl", "initials": "K", "orcid": "0000-0003-2815-1217", "researcher": {"href": "https://publications.scilifelab.se/researcher/eff63868e95240f695d47e871e31947f.json"}}, {"family": "Hailer", "given": "Nils P", "initials": "NP", "orcid": "0000-0002-3233-2638", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8bb8c013184ef7b482ffe6f8f1380b.json"}}], "type": "journal article", "published": "2022-01-04", "journal": {"title": "J Bone Joint Surg Am", "issn": "1535-1386", "issn-l": null, "volume": "104", "issue": "7", "pages": "610-620"}, "abstract": "The risk of revision surgery following total joint arthroplasty (TJA) may be influenced by genetic factors. Therefore, we sought to identify genetic variants associated with the risk of revision surgery in a genomewide association study.\r\n\r\nWe investigated a cohort of 1,130 twins from the Swedish Twin Registry treated with TJA. During a mean of 9.4 years of follow-up, 75 individuals underwent revision surgery for aseptic loosening (the primary outcome) and 94, for any reason (the secondary outcome). Genetic information was collected using the Illumina OmniExpress and PsychArray panels, and the Haplotype Reference Consortium served as the reference for gene imputation. Adjusted Cox regression models were fitted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).\r\n\r\nNine single-nucleotide polymorphisms (SNPs) reached genomewide significance for aseptic loosening. The first SNP, rs77149046, located in the endosome-lysosome associated apoptosis and autophagy regulator family member 2 (ELAPOR2) gene, conferred an HR of 5.40 (CI, 3.23-9.02; p = 1.32\u00d710-10), followed by 4 SNPs within the region coding for sodium-dependent taurine and beta-alanine transporter (SLC6A6), with HRs ranging from 3.35 to 3.43. The sixth SNP, rs7853989 (HR, 3.46; CI, 2.33-5.13; p = 6.91\u00d710-10), was located in a region coding for the ABO blood group system. This SNP has been described as predictive for blood type B. Seven significant SNPs were found for the risk of revision for any reason, with the first 4 again being located in the SLC6A6 region. The leading SNP, rs62233562, conferred an HR of 3.11 (CI, 2.19-4.40; p = 1.74\u00d710-10) for revision surgery. Similar HRs were found for SNPs 3:14506680 (p = 1.78\u00d710-10), rs2289129 (p = 1.78\u00d710-10), and rs17309567 (p = 3.16\u00d710-10). The fifth SNP, rs11120968, was located in the calmodulin-binding transcription activator 1 (CAMTA1) gene (HR, 2.34; CI, 1.74-3.13, p = 1.45\u00d710-8).\r\n\r\nWe identified 12 unique SNPs associated with an increased risk of revision surgery. Among these, 2 were in ELAPOR2, which is closely linked to bone formation. Another SNP is located in a gene region encoding for the ABO system, which merits further studies of causal relationships.\r\n\r\nPrognostic Level III. See Instructions for Authors for a complete description of levels of evidence.", "doi": "10.2106/JBJS.21.00750", "pmid": "34982741", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "00004623-990000000-00431"}], "notes": [], "created": "2022-01-20T12:59:36.162Z", "modified": "2024-01-16T13:48:37.826Z"}]}