Fracture-related infection: Prevalence and application of the new consensus definition in a cohort of 1004 surgically treated ankle fractures

Background Surgical treatment of ankle fractures comes with a substantial risk of complications, including infection. An unambiguously definition of fracture-related infections (FRI) has been missing. Recently, FRI has been defined by a consensus group with a diagnostic algorithm containing suggestive and confirmatory criteria. The aim of the current study was to report the prevalence of FRI in patients operated for ankle fractures and to assess the applicability of the diagnostic algorithm from the consensus group. Patients and methods Records of all patients with surgically treated ankle fractures from 2015 to 2019 were retrospectively reviewed for signs of postoperative infections. Patients with suspected infection were stratified according to confirmatory or suggestive criteria of FRI. Rate of FRI among patients with confirmatory and suggestive criteria were calculated. Results Suspected infection was found in 104 (10%) out of 1004 patients. Among those patients, confirmatory criteria were met in 76/104 (73%) patients and suggestive criteria were met in 28/104 (27%) at first evaluation. Patients with clinical confirmatory criteria (N = 76) were diagnosed with FRI. Patients with suggestive criteria were further examined with either bacterial sampling at the outpatient clinic, revision surgery including bacterial sampling, or a wait-and-see approach. Eleven (39%) of the 28 patients had positive cultures and were therefore diagnosed as having FRI at second evaluation. In total 87 (9%) patients were diagnosed with FRI according to the consensus definition. Only 73 (70%) of the 104 patients with suspected FRI had adequate bacterial sampling. Conclusion The prevalence of FRI, applying the FRI-consensus criteria, for patients with surgically treated ankle fractures was 9%. Twenty-two percent of patients who met the confirmatory criteria had negative bacterial cultures. The current study shows that we did not have a systematic approach to patients with suspected FRI as recommended by the consensus group. A systematic approach to adequate bacterial sampling when FRI is suspected is paramount. The consensus definition of FRI and its diagnostic algorithm facilitates such an approach.publishedVersio

Risk factors for fracture-related infection after ankle fracture surgery

Introduction Ankle fracture surgery comes with a risk of fracture-related infection (FRI). Identifying risk factors are important in preoperative planning, in management of patients, and for information to the individual patient about their risk of complications. In addition, modifiable factors can be addressed prior to surgery. The aim of the current paper was to identify risk factors for FRI in patients operated for ankle fractures. Methods A cohort of 1004 patients surgically treated for ankle fractures at Haukeland University Hospital in the period of 2015–2019 was studied retrospectively. Patient charts and radiographs were assessed for the diagnosis of FRI. Binary logistic regression was used in analyses of risk factors. Regression coefficients were used to calculate the probability for FRI based on the patients’ age and presence of one or more risk factors. Results FRI was confirmed in 87 (9%) of 1004 patients. Higher age at operation (p < .001), congestive heart failure (CHF), p = 0.006), peripheral artery disease (PAD, p = 0.001), and current smoking (p = .006) were identified as risk factors for FRI. PAD and CHF were the risk factors displaying the strongest association with FRI with an adjusted odds ratio of 4.2 (95% CI 1.8–10.1) and 4.7 (95% CI 1.6–14.1) respectively. Conclusion The prevalence of FRI was 9% after surgical treatment of ankle fractures. The combination of risk factors found in this study demonstrate the need for a thorough, multidisciplinary, and careful approach when faced with an elderly or frail patient with an ankle fracture. The results of this study help the treating surgeons to inform their patients of the risk of FRI prior to ankle fracture surgery.publishedVersio

Single PFAS and PFAS mixtures affect nuclear receptor- and oxidative stress-related pathways in precision-cut liver slices of Atlantic cod (Gadus morhua)

The aim of the present study was to investigate effects of per- and polyfluoroalkyl substances (PFAS), both single compounds and a mixture of these, using precision-cut liver slices (PCLS) from Atlantic cod (Gadus morhua). PCLS were exposed for 48 h to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) (10, 50 and 100 μM), and three mixtures of these at equimolar concentrations (10, 50 and 100 μM). Transcriptomic responses were assessed using RNA sequencing. Among exposures to single PFAS, PFOS produced the highest number of differentially expressed genes (DEGs) compared to PFOA and PFNA (86, 25 and 31 DEGs, respectively). Exposure to the PFAS mixtures resulted in a markedly higher number of DEGs (841). Clustering analysis revealed that the expression pattern of the PFAS mixtures were more similar to PFOS compared to PFOA and PFNA, suggesting that effects induced by the PFAS mixtures may largely be attributed to PFOS. Pathway analysis showed significant enrichment of pathways related to oxidative stress, cholesterol metabolism and nuclear receptors in PFOS-exposed PCLS. Fewer pathways were significantly enriched following PFOA and PFNA exposure alone. Significantly enriched pathways following mixture exposure included lipid biosynthesis, cancer-related pathways, nuclear receptor pathways and oxidative stress-related pathways such as ferroptosis. The expression of most of the genes within these pathways was increased following PFAS exposure. Analysis of non-additive effects in the 100 μM PFAS mixture highlighted genes involved in the antioxidant response and membrane transport, among others, and the majority of these genes had synergistic expression patterns in the mixture. Nevertheless, 90% of the DEGs following mixture exposure showed additive expression patterns, suggesting additivity to be the major mixture effect. In summary, PFAS exposure promoted effects on cellular processes involved in oxidative stress, nuclear receptor pathways and sterol metabolism in cod PCLS, with the strongest effects observed following PFAS mixture exposure.publishedVersio

Association of Delayed Surgery for Ankle Fractures and Patient-Reported Outcomes

Background: Several studies probe the association between prolonged time to surgery and postoperative complications in ankle fractures, but little is known about how a longer wait time affects clinical outcomes. The present study aims to assess the association between time from injury to surgery and patient-reported outcomes after operative treatment of severe ankle fractures. Method: Patients treated operatively for low-energy ankle fractures that also involve the posterior malleolus from 2014 to 2016 were included. Patient charts were reviewed for patient demographics, type of trauma, fracture characteristics, treatment given, and complications. Ankle function was evaluated on a follow-up visit by clinical examination, radiographs, and patient-reported outcome measures (Self-Reported Foot and Ankle Score [SEFAS], RAND-36, visual analog scale [VAS] of Pain, VAS of Satisfaction). We compared patients treated within 1 week to those treated later than a week from injury for analyses. Results: Follow-up visits of 130 patients were performed at mean 26 (SD 9) months after surgery. Patient demographics and fracture characteristics were similar between groups. Mean SEFAS was 34 (SD 10) in patients treated later than a week from injury vs 38 (SD 9) in those treated earlier (P = .012). Patients operated on later than 7 days from injury reported more pain (P = .008) and lower satisfaction than those treated earlier (P = .016). Conclusion: In this retrospective patient series of low-energy ankle fractures with posterior malleolar fragments, we found that waiting >7 days for definitive surgery was associated with poorer clinical outcomes and more pain compared with those who had surgery earlier.publishedVersio

Perioperative, short, and long-term mortality related to fixation in primary total hip arthroplasty: a study of 79,557 patients in the Norwegian Arthroplasty Register

Background and purpose — There are reports on perioperative deaths in cemented total hip arthroplasty (THA), and THA revisions are associated with increased mortality. We compared perioperative (intraoperatively or within 3 days of surgery), short-term and long-term mortality after all-cemented, all-uncemented, reverse hybrid (cemented cup and uncemented stem), and hybrid (uncemented cup and cemented stem) THAs. Patients and methods — We studied THA patients in the Norwegian Arthroplasty Register from 2005 to 2018, and performed Kaplan–Meier and Cox survival analyses with time of death as end-point. Mortality was calculated for all patients, and in 3 defined risk groups: high-risk patients (age ≥ 75 years and ASA > 2), intermediate-risk patients (age ≥ 75 years or ASA > 2), low-risk patients (age < 75 years and ASA ≤ 2). We also calculated mortality in patients with THA due to a hip fracture, and in patients with commonly used, contemporary, well-documented THAs. Adjustement was made for age, sex, ASA class, indication, and year of surgery. Results — Among the 79,557 included primary THA patients, 11,693 (15%) died after 5.8 (0–14) years’ follow-up. Perioperative deaths were rare (30/105) and found in all fixation groups. Perioperative mortality after THA was 4/105 in low-risk patients, 34/105 in intermediate-risk patients, and 190/105 in high-risk patients. High-risk patients had 9 (CI 1.3–58) times adjusted risk of perioperative death compared with low-risk patients. All 4 modes of fixation had similar adjusted 3-day, 30-day, 90-day, 3–30 day, 30–90 day, 90-day–10-year, and 10-year mortality risk. Interpretation — Perioperative, short-term, and long-term mortality after primary THA were similar, regardless of fixation type. Perioperative deaths were rare and associated with age and comorbidity, and not type of fixation.publishedVersio

Fixation, sex, and age: highest risk of revision for uncemented stems in elderly women - data from 66,995 primary total hip arthroplasties in the Norwegian Arthroplasty Register

Background and purpose: There is no consensus on best method of fixation in hip arthroplasty. We investigated different modes of fixation in primary total hip arthroplasty (THA) and the influence of age and sex, to assess need for a differentiated approach. Patients and methods: The study was based on data from the Norwegian Arthroplasty Register in the period 2005–2017. Included were all-cemented, all-uncemented, reverse hybrid (uncemented stem and cemented cup), and hybrid (cemented stem and uncemented cup) THA designs that were commonly used, contemporary and well documented, using different causes of revision as endpoints. Results: From the included 66,995 primary THAs, 2,242 (3.3%) were revised. Compared with all-cemented THAs, all-uncemented had a higher risk of revision due to any cause (RR 1.4; CI 1.2–1.6), mainly due to an increased risk of periprosthetic fracture (RR 5.2; CI 3.2–8.5) and dislocation (RR 2.2; CI 1.5–3.0). Women had considerably higher risk of revision due to periprosthetic fracture after all-uncemented THA (RR 12; CI 6–25), compared with cemented. All-uncemented THAs in women of age 55–75 years (RR 1.3; CI 1.0–1.7) and over 75 years of age (RR 1.8; CI 1.2–2.7), and reverse hybrid THAs in women over the age of 75 (RR 1.5; CI 1.1–1.9) had higher risk of revision compared with cemented. Hybrid THAs (RR 1.0; CI 0.9–1.2) and reverse hybrid THAs (RR 1.0; CI 0.7–1.3) had similar risk of revision due to any cause as cemented THAs. Interpretation: Uncemented stems (all-uncemented and reverse hybrid THAs) had increased risk of revision in women over 55 years of age, mainly due to periprosthetic fracture and dislocation, and should probably not be used in THA in these patients.publishedVersio

No difference in risk of revision due to infection between clindamycin and cephalosporins as antibiotic prophylaxis in cemented primary total knee replacements: a report from the Norwegian Arthroplasty Register 2005–2020

Background and purpose: Systemic antibiotic prophylaxis with clindamycin, which is often used in penicillin- or cephalosporin-allergic patients’, has been associated with a higher risk of surgical revision for deep prosthetic joint infection (PJI) than cloxacillin in primary total knee replacement (TKR). We aimed to investigate whether clindamycin increases the risk of surgical revisions due to PJI compared with cephalosporins in primary cemented TKR. Patients and methods: Data from 59,081 TKRs in the Norwegian Arthroplasty Register (NAR) 2005–2020 was included. 2,655 (5%) received clindamycin and 56,426 (95%) received cephalosporins. Cox regression analyses were performed with adjustment for sex, age groups, diagnosis, and ASA score. Survival times were calculated using Kaplan–Meier estimates and compared using Cox regression with revision for PJI as endpoint. The cephalosporins cefalotin and cefazolin were also compared. Results: Of the TKRs included, 1.3% (n = 743) were revised for PJI. 96% (n = 713) had received cephalosporins and 4% (n = 30) clindamycin for perioperative prophylaxis. Comparing cephalosporins (reference) and clindamycin, at 3-month follow-up the adjusted hazard ratio rate (HRR) for PJI was 0.7 (95% confidence interval [CI] 0.4–1.4), at 1 year 0.9 (CI 0.6–1.5), and at 5 years 0.9 (CI 0.6–1.4). Analysis using propensity score matching showed similar results. Furthermore, comparing cefalotin (reference) and cefazolin, HRR was 1.0 (CI 0.8–1.4) at 3 months and 1.0 (CI 0.7–1.3) at 1-year follow-up. Conclusion: We found no difference in risk of revision for PJI when using clindamycin compared with cephalosporins in primary cemented TKRs. It appears safe to continue the use of clindamycin in penicillin- or cephalosporin-allergic patients.publishedVersio

Kaplan-Meier and Cox Regression Are Preferable for the Analysis of Time to Revision of Joint Arthroplasty: Thirty-One Years of Follow-up for Cemented and Uncemented THAs Inserted from 1987 to 2000 in the Norwegian Arthroplasty Register

Background: Previous studies have suggested that the probability function of 1 minus the Kaplan-Meier survivorship overestimates revision rates of implants and that patient death should be included in estimates as a competing risk factor. The present study aims to demonstrate that this line of thinking is incorrect and is a misunderstanding of both the Kaplan-Meier method and competing risks. Methods: This study demonstrated the differences, misunderstandings, and interpretations of classical, competing-risk, and illness-death models with use of data from the Norwegian Arthroplasty Register for 15,734 cemented and 7,867 uncemented total hip arthroplasties (THAs) performed from 1987 to 2000, with fixation as the exposure variable. Results: The mean age was higher for patients who underwent cemented (72 years) versus uncemented THA (53 years); as such, a greater proportion of patients who underwent cemented THA had died during the time of the study (47% compared with 29%). The risk of revision at 20 years was 18% for cemented and 42% for uncemented THAs. The cumulative incidence function at 20 years was 11% for cemented and 36% for uncemented THAs. The prevalence of revision at 20 years was 6% for cemented and 31% for uncemented THAs. Conclusions: Adding death as a competing risk will always attenuate the probability of revision and does not correct for dependency between patient death and THA revision. Adjustment for age and sex almost eliminated differences in risk estimates between the different regression models. In the analysis of time until revision of joint replacements, classical survival analyses are appropriate and should be advocated.publishedVersio

Increasing but levelling out risk of revision due to infection after total hip arthroplasty: a study on 108,854 primary THAs in the Norwegian Arthroplasty Register from 2005 to 2019

Background and purpose — Focus on prevention, surveillance, and treatment of infection after total hip arthroplasty (THA) in the last decade has resulted in new knowledge and guidelines. Previous publications have suggested an increased incidence of surgical revisions due to infection after THA. We assessed whether there have been changes in the risk of revision due to deep infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005–2019. Patients and methods — Primary THAs reported to the NAR from January 1, 2005 to December 31, 2019 were included. Adjusted Cox regression analyses with the first revision due to deep infection after primary THA were performed. We investigated changes in the risk of revision as a function of time of primary THA. Time was stratified into 5-year periods. We studied the whole population of THAs, and the subgroups: all-cemented, all-uncemented, reverse hybrid (cemented cup), and hybrid THAs (cemented stem). In addition, we investigated factors that were associated with the risk of revision, and changes in the time span from primary THA to revision. Results — Of the 108,854 primary THAs that met the inclusion criteria, 1,365 (1.3%) were revised due to deep infection. The risk of revision due to infection, at any time after primary surgery, increased through the period studied. Compared with THAs implanted in 2005–2009, the relative risk of revision due to infection was 1.4 (95% CI 1.2–1.7) for 2010–2014, and 1.6 (1.1–1.9) for 2015–2019. We found an increased risk for all types of implant fixation. Compared to 2005–2009, for all THAs, the risk of revision due to infection 0–30 days postoperatively was 2.2 (1.8–2.8) for 2010–2014 and 2.3 (1.8–2.9) for 2015–2019, 31–90 days postoperatively 1.0 (0.7–1.6) for 2010–2014 and 1.6 (1.0–2.5) for 2015–2019, and finally 91 days–1 year postoperatively 1.1 (0.7–1.8) for 2010–2014 and 1.6 (1.0–2.6) for 2015–2019. From 1 to 5 years postoperatively, the risk of revision due to infection was similar to 2005–2009 for both the subsequent time periods Interpretation — The risk of revision due to deep infection after THA increased throughout the period 2005–2019, but appears to have levelled out after 2010. The increase was mainly due to an increased risk of early revisions, and may partly have been caused by a change of practice rather than a change in the incidence of infection.publishedVersio