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Background: Oxaliplatin-induced peripheral neuropathy negatively affects the quality of life for patients with gastrointestinal cancers and may cause neuropathic pain. Measures of peripheral nerve structure or function, such as intraepidermal nerve fiber density (IENFD) during treatment could reduce neuropathy severity through individualized dose reduction. Objective: The aim was to evaluate the predictive values of IENFD, quantitative sensory testing (QST), and nerve conduction studies (NCS) for significant neuropathy and neuropathic pain. Methods: Fifty-five patients were examined prospectively before, during, and six months following treatment using skin biopsies, QST and NCS. Clinically significant neuropathy six months after treatment was defined as reduced Total Neuropathy Score of more than five and neuropathic pain was assessed according to International Association for the Study of Pain criteria. Results: Thirty patients had a clinically significant neuropathy, and 14 had neuropathic pain. Vibration detection threshold (VDT) before treatment was correlated with clinically significant neuropathy six months after treatment (OR 0.54, p = 0.01) and reductions in cold detection threshold (CDT) after 25% of treatment (OR 1.38, p = 0.04) and heat pain threshold (HPT) after 50% of treatment (OR 1.91, p = 0.03) with neuropathic pain. Cut off values of 5 for baseline VDT and changes of more than –0.05 °C and –0.85 °C in CDT and HPT were estimated. Sensitivity and specificity was low to moderate. There was no correlation between changes in IENFD or NCS and significant neuropathy or neuropathic pain. Conclusions: Vibration detection thresholds and thermal detection thresholds may be useful for prediction of clinically significant and painful neuropathy, respectively. However, low to moderate sensitivity and specificity may limit the predictive value in clinical practice.

Clinical forensic assessments of injuries’ life-threatening danger may have an impact on the legal aftermath following a violent assault. The pursuit of evidence-based guidelines should ensure a user-independent and reproducible forensic practice. However, does it? The aim of this study was to evaluate the forensic life-threatening danger assessments after a protocol implementation in 2016. The evaluation concerned usability and reproducibility of the protocol, and its influence on assessment severity. We analyzed the level of inter- and intra-rater agreement using 169 blinded, prior-protocol cases that were reassessed by two forensic specialists. We compared assessment made the year before and after protocol implementation (n = 262), and the forensic specialists’ reassessments with the prior-protocol cases’ original assessments (n = 169). Whether to make an assessment, the levels of agreement varied between weak agreement (inter-rater, Κ = 0.43; assessor 1, Κ = 0.57) and strong agreement (assessor 2, Κ = 0.90). Regarding severity, the levels of agreement varied between strong agreement (inter-rater, Κ = 0.87; assessor 1: Κ = 0.90) and almost perfect agreement (assessor 2: Κ = 0.94). The assessments were statistically significant redistributed after the implementation (chi-square test: p

Objective To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty. Design Randomised, blinded, placebo controlled trial with follow-up at 90 days. Setting Five Danish hospitals, September 2018 to March 2020. Participants 485 adult participants undergoing total knee arthroplasty. Intervention A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia. Main outcome measures The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P Results 485 participants were randomised: 161 to DX1, 162 to DX2, and 162 to placebo. Data from 472 participants (97.3%) were included in the primary outcome analysis. The median (interquartile range) morphine consumptions at 0-48 hours were: DX1 37.9 mg (20.7 to 56.7); DX2 35.0 mg (20.6 to 52.0); and placebo 43.0 mg (28.7 to 64.0). Hodges-Lehmann median differences between groups were: −2.7 mg (98.3% confidence interval −9.3 to 3.7), P=0.30 between DX1 and DX2; 7.8 mg (0.7 to 14.7), P=0.008 between DX1 and placebo; and 10.7 mg (4.0 to 17.3), P Conclusion Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain. Trial registration Clinicaltrials.gov NCT03506789 .

Background and purpose ��� Patients having a knee arthroplasty revision for the indication ���pain without loosening��� may have a higher risk of re-revisions than patients revised for other indications. The primary aim of this study was to compare the survival of knee arthroplasties revised for ���pain without loosening��� compared with ���aseptic loosening.��� The second was to investigate the prosthesis survival rates in 3 surgical subgroups (total knee arthroplasty (TKA)���TKA; partial revision (revision of tibial or femoral component); unicompartmental knee arthroplasty���TKA) and to compare the prosthesis survival rates for 1997���2009 and 2010���2018. Patients and methods ��� 4,299 revisions were identified in the period 1997���2018 from the Danish Knee Arthroplasty Register. Of these, 1,111 (26%) were performed due to ���pain without loosening��� without any other indications, 674 (16%) due to ���pain without loosening��� combined with other indications, and 2,514 (59%) due to ���aseptic loosening���. Survival analysis was performed by a Cox multivariate analysis and Kaplan���Meier curves were presented. Results ��� The cumulated proportions of re-revision after 2, 5, and 20 years were 12% (95% CI 10���14), 18% (CI 16���20), and 23% (CI 20���25) for ���pain without loosening��� versus 11% (CI 9.3���12), 16% (CI 14���17), and 19% (CI 18���21) for ���aseptic loosening.��� There were no statistically significant differences between the 2 indications in repeated analyses for each of the surgical subgroups. The hazard ratio for re-revision comparing ���pain without loosening��� with ���aseptic loosening��� was 1.03 (CI 0.87���1.2). The 8-year risk of re-revision for ���pain without loosening��� was 22% (CI 19���26) versus 22% (CI 20���25) for ���aseptic loosening��� in the period from 1997���2009, and 18% (CI 15���22) versus 14% (CI 13���16) in the period from 2010���2018. Interpretation ��� The risk of re-revision was similar for patients having a knee arthroplasty revision for the indication ���pain without loosening��� compared with ���aseptic loosening.��� However, we observed a slight improvement of prosthesis survival rates after revisions for both indications from 1997���2009 to 2010���2018. We cannot recommend for or against revision in cases with ���pain without loosening��� based on these data alone.

Background and purpose — Bone remodeling as a response to bone trauma, postoperative immobilization, and device-related bone reactions can lead to loss of bone stock and increase the risk of periprosthetic fracture and aseptic loosening. This study investigates the adaptive bone remodeling of the proximal tibia after uncemented total knee arthroplasty (TKA). Patients and methods — We performed a 2-year follow up of 53 patients (mean age 62 (38–70) years, 27 of whom were men, who received an uncemented TKA in a randomized controlled trial with bone mineral density (BMD) as secondary endpoint. Patients were randomized to 2 groups of either monoblock (A) or modular (B) polyethylene design. The TKAs were performed using the uncemented Zimmer Nexgen trabecular metal. Measurements of BMD were done postoperatively and after 3, 6, 12, and 24 months. BMD was measured in 3 regions of interest (ROI). Results and interpretation — In group A statistically significant changes in BMD were seen after 24 months in both the medial and lateral ROI. BMD decreased medially by 15% (p = 0.004) and laterally by 13% (p = 0.01). In group B the BMD changes were limited and after 24 months returned to the preoperative values. The differences in BMD change between groups were statistically significant in both the medial (p = 0.03) and lateral (p = 0.02) ROI. In the distal ROI we found no significant change in BMD in either group. A significantly different bone remodeling pattern of the proximal tibia was seen in the 2 groups with a higher degree of bone loss in the knees that received the monoblock polyethylene design, indicating that the flexible monoblock implant design, previously shown to improve fixation, does not decrease the bone loss of the proximal tibia. Trial registration:ClinicalTrials.gov identifier: NCT01637051.

Dental health care professionals have the opportunity to play a key role in tobacco prevention and cessation among adolescents. Snus use has increased in Norway, especially in the age group 16–24, whereas there has been a decline in smoking. This study investigated attitudes and activities related to snus prevention among dental health care professionals working in the Public Dental Service (PDS) in south‐eastern Norway. A web‐based survey with a total of 557 dentists and dental hygienists in seven counties in Norway, with a response rate of 53.5%, was carried out in 2017. Dentists' and dental hygienists' activities regarding preventive snus use intervention were analysed using the chi‐square test. Intervention was measured with a score (1–5) based on four questions. Bivariate and multivariate linear regression analyses were used to investigate the associations between the explanatory variables of attitudes/activities and the outcome intervention variable. Approximately 87% of the dentists and 58% of the dental hygienists were not familiar with the “minimum intervention method” for tobacco prevention and cessation. Dental hygienists were most active in informing and supporting their patients in prevention and cessation of snus use. The PDS is an underutilized arena for tobacco prevention and cessation among adolescents, and the intervention potential is particularly high among the dentists.

BACKGROUND: Knee fractures may lead to post-traumatic knee osteoarthritis and subsequent TKA in some patients. However, absolute risk estimates and risk factors for TKA in patients with knee fractures compared with those of the general population remain largely unknown. Such knowledge would help establish the treatment burden and direct patient counseling after a knee fracture is sustained.QUESTIONS/PURPOSES: (1) What is the short-term risk of TKA after knee fracture? (2) What is the long-term risk of TKA after knee fracture? (3) What are the risk factors for TKA in patients with knee fractures?METHODS: A nationwide 20-year, matched-case comparison cohort study of prospectively collected data from the Danish National Patient Registry included all patients at least 15 years old with International Classification of Diseases, 10th revision codes DS724, DS820, or DS821 (knee fractures) on the date their knee fracture was registered. Each patient with a knee fracture was matched (by sex and age) to five people without knee fractures from the general Danish population on the date the knee fracture patient's knee fracture was registered (population controls). Patients with knee fractures and people in the population control group were followed from the date the knee fracture patient's knee fracture was registered to the date of TKA, amputation, knee fusion, emigration, death, or end of follow-up in April 2018. TKA risks for patients with knee fractures versus those for population controls and TKA risk factors in patients with knee fractures were estimated using hazard ratios (HRs) with 95% CIs. A total of 48,791 patients with knee fractures (median age 58 years [interquartile range 41-73]; 58% were female) were matched to 263,593 people in the population control group.RESULTS: The HR for TKA in patients with knee fractures compared with population controls was 3.74 (95% CI 3.44 to 4.07; p < 0.01) in the first 3 years after knee fracture. Among knee fracture patients, the risk of undergoing TKA was 2% (967 of 48,791) compared with 0.5% (1280 of 263,593) of people in the population control group. After the first 3 years, the HR was 1.59 (95% CI 1.46 to 1.71) and the number of patients with knee fractures with TKA events divided by the number at risk was 2% (849 of 36,272), compared with 1% (2395 of 180,418) of population controls. During the 20-year study period, 4% of patients with knee fractures underwent TKA compared with 1% of population controls. Risk factors for TKA in patients with knee fractures were: primary knee osteoarthritis (OA) versus no primary knee OA (HR 9.57 [95% CI 5.39 to 16.98]), surgical treatment with external fixation versus open reduction and internal fixation and reduction only (HR 1.92 [95 % CI 1.01 to 3.66]), proximal tibia fracture versus patellar fracture (HR 1.75 [95 % CI 1.30 to 2.36]), and distal femur fracture versus patellar fracture (HR 1.68 [95 % CI 1.08 to 2.64]). Surgical treatment of knee fractures was also a risk factor for TKA. The HRs for TKA in patients with knee fractures who were surgically treated versus those who were treated non-surgically were 2.05 (95% CI 1.83 to 2.30) in the first 5 years after knee fracture and 1.19 (95% CI 1.01 to 1.41) after 5 years.CONCLUSIONS: Patients with knee fractures have a 3.7 times greater risk of TKA in the first 3 years after knee fracture, and the risk remains 1.6 times greater after 3 years and throughout their lifetimes. Primary knee OA, surgical treatment of knee fractures, external fixation, proximal tibia fractures, and distal femur fractures are TKA risk factors. These risk estimates and risk factors highlight the treatment burden of knee fractures, building a foundation for future studies to further counsel patients on their risk of undergoing TKA based on patient-, fracture-, and treatment-specific factors.LEVEL OF EVIDENCE: Level III, prognostic study.

BackgroundThe external validity of randomized controlled trials (RCTs) is critical for the relevance of trial results in a clinical setting. We aimed to assess the external validity of RCTs investigating postoperative pain treatment after total hip and knee arthroplasty (THA and TKA) by comparing patient characteristics in these trials with a clinical cohort. Further, we assessed the use of exclusion criteria of the included RCTs.MethodsWe searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant RCTs up to June 2019. Data on patient characteristics from this research population were compared with an unselected clinical cohort from the Danish Hip and Knee Arthroplasty Registries in the period 2005–2019. Trends in patient characteristics and the use of exclusion criteria were assessed with control charts.ResultsIn total, 550 RCTs with 48 962 participants were included in the research cohort. The clinical cohort included 101 439 THA patients and 90 505 TKA patients. Patient characteristics (age, body mass index (BMI), American Society of Anesthesiologists (ASA) score and sex distribution) in the research cohort resembled those of the clinical cohort. Age, BMI and ASA scores did not change over time in the research cohort. In the clinical cohort, age increased among both THA and TKA patients, and BMI and ASA scores increased among TKA patients. Most commonly used exclusion criteria in the RCTs were high ASA score (62%), older age (45%), obesity (32%) and chronic opioid use (41%). Exclusion of chronic opioid users and individuals with obesity increased over time.ConclusionPatient characteristics in research trials investigating postoperative pain management after THA and TKA currently resemble those of a clinical cohort. However, individuals in the clinical cohort are getting older, and TKA patients more obese with increasing ASA scores. Concomitantly, RCTs increase the tendency to exclude patients with older age, obesity, chronic pain and/or opioid use. This trending discrepancy can hinder the generalizability of future research results, and therefore increased focus on pragmatic trials resembling real-world conditions are needed.PROSPERO registration numberCRD42019125691

Preclinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological modulation of inflammatory cytokines in ischemic stroke. Experimental evidence shows that targeting tumor necrosis factor (TNF) and interleukin (IL)-1 holds promise, and these cytokines are considered prime targets in the development of new stroke therapies. So far, however, information on the cellular expression of TNF and IL-1 in the human ischemic brain is sparse.We studied 14 cases of human post-mortem ischemic stroke, representing 21 specimens of infarcts aged 1 to > 8 days. We characterized glial and leukocyte reactions in the infarct/peri-infarct (I/PI) and normal-appearing tissue (NAT) and the cellular location of TNF, TNF receptor (TNFR)1 and TNFR2, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1Ra). The immunohistochemically stained tissue sections received a score reflecting the number of immunoreactive cells and the intensity of the immunoreactivity (IR) in individual cells where 0 = no immunoreactive cells, 1 = many intermediately to strongly immunoreactive cells, and 2 = numerous and intensively immunoreactive cells. Additionally, we measured blood TNF, TNFR, and IL-1 levels in surviving ischemic stroke patients within the first 8 h and again at 72 h after symptom onset and compared levels to healthy controls.We observed IL-1α and IL-1β IR in neurons, glia, and macrophages in all specimens. IL-1Ra IR was found in glia, in addition to macrophages. TNF IR was initially found in neurons located in I/PI and NAT but increased in glia in older infarcts. TNF IR increased in macrophages in all specimens. TNFR1 IR was found in neurons and glia and macrophages, while TNFR2 was expressed only by glia in I/PI and NAT, and by macrophages in I/PI. Our results suggest that TNF and IL-1 are expressed by subsets of cells and that TNFR2 is expressed in areas with increased astrocytic reactivity. In ischemic stroke patients, we demonstrate that plasma TNFR1 and TNFR2 levels increased in the acute phase after symptom onset compared to healthy controls, whereas TNF, IL-1α, IL-1β, and IL-1Ra did not change.Our findings of increased brain cytokines and plasma TNFR1 and TNFR2 support the hypothesis that targeting post-stroke inflammation could be a promising add-on therapy in ischemic stroke patients.

Objectives: To investigate the effects of lower limb strength training in addition to neuromuscular exercise and education (ST + NEMEX-EDU) compared to neuromuscular exercise and education alone (NEMEX-EDU) on self-reported physical function in patients with knee osteoarthritis (KOA). Design: Patient-blinded, parallel-group randomized controlled trial (RCT). Methods: The trial included 90 patients in secondary care with radiographic and symptomatic KOA, ineligible for knee replacement. Both groups exercised twice weekly for 12 weeks. Additional strength training consisted of a single, fatiguing knee extension set (30-60RM) before four sets of leg-press (8-12RM). Primary outcome was the between-group difference on the subscale activities of daily living from the Knee Injury and Osteoarthritis Outcome Score (KOOSADL) at 12 weeks. Secondary outcomes included KOOS symptoms, pain, function in sport and recreation, and quality of life, 40 m walk, stair climb, leg extension power, EuroQol-5D-5L, pain medication usage, and adverse events. Results: There was no statistically significant between-group difference in KOOSADL at 12-weeks; adjusted mean difference −1.15 (−6.78 to 4.48). Except for the stair climb test, which demonstrated an adjusted mean difference of 1.15 (0.09–2.21) in favor of ST + NEMEX-EDU, all other outcomes showed no statistically significant between-group differences. Neither group improved leg extension power. Conclusion: The addition of lower-limb strength training, using a low-dose approach, to neuromuscular exercise and education carried no additional benefits on self-reported physical function or on most secondary outcomes. Both groups displayed similar improvements at 12-week follow-up. Hence, the current low-dose strength training approach provided no additional clinical value in this group of KOA patients. Trial identifier (ClinicalTrials.gov): NCT03215602.

PURPOSE: To examine the association between use of statins and risk of deterioration of peripheral nerve function.METHODS: We prospectively followed patients who initiated statin treatment and compared them with statin never-users (non-users). At the time of inclusion and at 1-year follow-up, participants underwent tests for peripheral nerve function (ie nerve conduction studies, quantitative sensory testing), skin biopsies and ratings of symptoms and signs of neuropathy. We selected five tests of nerve function and the intraepidermal nerve fibre density (IENFD) a priori as primary outcomes. We used linear regression to test for differences between statin users and non-users with Holm-Bonferroni-corrected statistical significance level of .05.RESULTS: Comparisons were based on 57 statin users and 46 non-users. Changes in nerve function test results during follow-up were not uniform with regard to direction and were statistically not significant with the exception of IENFD (change in IENFD: statin users 1 fibre/mm vs. non-statin users -2 fibres/mm; P-value = .006). None of the participants developed overt peripheral neuropathy. However, five statin users developed neuropathy-like symptoms and a post hoc analysis showed a significant decrease in vibration sensitivity compared to asymptomatic statin users.CONCLUSION: Statin use was not clearly associated with increased risk of deterioration of peripheral nerve function analysed at a group level. However, given the sample size limitations of our study and the findings of our post hoc analysis, we cannot preclude that peripheral nerve function may be affected in some individuals exposed to statins.

OBJECTIVE: This study investigated how desmopressin is prescribed to adults in Denmark.METHODS: All adult users of desmopressin over an 8-year period were identified from the Danish National Prescription Registry. Adult patients with nocturia or nocturnal enuresis (NE) were identified by indication codes for "frequent nocturnal voiding" or "involuntary nocturnal voiding", respectively. Patient demographics, desmopressin formulation and dose, and concomitant medication were investigated.RESULTS: In all, 13 871 adults with nocturia and 2872 adults with chronic (i.e. >10 prescriptions) NE were given 102 547 and 43 712 desmopressin prescriptions, respectively. Across the entire patient cohort, 57% were women and mean patient age was 62 years. Over 40% of prescriptions were to elderly patients (≥65 years), and desmopressin use for adult enuresis increased with age. Orally disintegrating tablets were the most frequently used formulation (57%-65% of prescriptions), and a greater proportion of women than men used low-dose desmopressin (60 μg). Concomitant use of painkillers (opioids: 18%-26.7% of prescriptions; non-steroidal anti-inflammatory drugs: 14.2%-16.4% of prescriptions) and antidepressants (14.4%-18.1% of prescriptions) was common in both conditions, and 5.4%-9.2% of concomitant prescriptions were for overactive bladder medications.CONCLUSIONS: This study provides insights into desmopressin use among Danish adults. Nearly half the prescriptions were to patients aged ≥65 years, despite historical manufacturer recommendations that desmopressin be restricted to patients

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double‐blinded, placebo‐controlled study, we investigated the effects of six‐month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin‐stimulated Rd) and body composition were assessed by euglycemic‐hyperinsulinemic clamp and dual X‐ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ = −0.43; p = 0.003). Δ‐mitochondrial fraction correlated positively with Δ‐total testosterone (ρ = 0.70; p = 0.02), and Δ‐glycogen fraction correlated inversely with Δ‐LBM (ρ = −0.83; p = 0.002) during six‐month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small‐scale study, the beneficial effects of six‐month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six‐month ST or combined three‐month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Loss of bone stock as a response to the bone trauma, immobilization, and stress shielding related to joint replacement surgery increases the risk of fracture of the distal femur after total knee arthroplasty. Previous studies of uncemented femoral components have reported very high levels of bone loss in the distal femur. This study investigates the adaptive bone remodeling of the distal femur after uncemented total knee arthroplasty. We performed a 2-year follow-up of 53 patients (mean age 61.5 [38–70] years, F/M = 27/26, body mass index 29.5) who because of osteoarthritis received an uncemented total knee arthroplasty. All patients received a NexGen CR-Flex Porous Femoral Component. Measurements of bone mineral density of the distal femur using dual-energy X-ray absorptiometry were performed postoperatively and after 3, 6, 12, and 24 months. Bone mineral density (g/cm 2 ) was measured in 3 regions of interest in the periprosthetic bone of the distal femur. Repeated measures analysis of variance and Tukey post hoc test for bone mineral density changed over time ( p p p p

Epicardial adipose tissue (EAT) may play a role in the development of coronary artery disease. The purpose of this study was to evaluate a method based on postmortem computed tomography (PMCT) for the estimation of EAT volume. We PMCT-scanned the eviscerated hearts of 144 deceased individuals, who underwent a medicolegal autopsy. Using Mimics® we performed segmentation of the images and obtained the volumes of EAT and myocardium. Total heart volume was calculated by adding the volumes of EAT and myocardium. Total heart weight, including EAT, myocardium and attached vessels, was measured during autopsy. Inter-observer analysis was performed on 30 randomly chosen subjects. We included 132 individuals in the results (age range: 22–94 years; 56% men). Twelve individuals were excluded due to inadequate PMCT scanning. Median EAT volume was 73.0 mL (Interquartile range; IQR: 45.6–113.7 mL) in men and 64.8 mL (IQR: 44.0–98.0 mL) in women, which accounted for 20.4 ± 10.2% and 21.9 ± 9.5% of total heart volume, respectively. This corresponded with former autopsy studies. Total heart volume measured by PMCT was highly correlated with heart weight (R2 = 90%). Mean inter-observer difference of EAT volume was −1.7 mL (95% limits of agreement: −37.0-33.6 mL), with an Intra Class Correlation of 0.91. It was possible to estimate EAT volume using PMCT on eviscerated human hearts. Our method was fast and accurate with good inter-observer agreement. This is a useful method to determine EAT at autopsy, and we will apply this method in future research.

Background: Psychiatric conditions and psychopharmacological treatments have been demonstrated to be important risk-factors for prolonged hospital length of stay, readmission and morbidity, following fast-track total hip (THA) and total knee arthroplasty (TKA). Aims: The aim of the study was to provide a detailed description of the preoperative psychiatric characteristics of a well-defined patient population undergoing THA and TKA, using the 90-item Symptom Checklist (SCL-90-R). Methods: A pre-surgical population of 2183 patients completed the full SCL-90-R prior to THA/TKA from 2015 to 2016. The SCL-90-R scale and total scores of the pre-surgical sample were compared to the scores of an age- and gender stratified Danish sample of healthy controls. A Mokken scalogram analysis was conducted to assess the scalability of the SCL-90-R in both samples. Results: The Mokken analysis yielded acceptable scalability coefficients above 0.30 in all subscales of the SCL-90-R except psycoticism (0.28). There was no clinically significant difference (effect size =

BACKGROUND: Revision of infected knee arthroplasties is associated with high failure rates (30-40%). An understanding of the microbiology is important to optimize treatment and outcome. We describe microbiological diagnostic practice and diagnosis in revision of infected knee arthroplasties.METHODS: One hundred and two partial revisions (open debridement and exchange of tibial insert) and 213 two-stage procedures performed due to infection in 275 patients from 1 July 2011 to 30 June 2013 were included and analysed by linkage to data from a nationwide registry on microbiological test results.RESULTS: 78 (24.8%) revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43 (14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15 revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin-resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent, sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50% and preoperative blood cultures were performed in 22% of cases. In 73% of the preoperative knee-aspirations bacteriological findings were fully or partially in accordance with intraoperative cultures. In 54% of the later re-revisions due to infection (treatment-failures) the cultured species differed from or was not detected at index revision surgery.CONCLUSIONS: The 25% culture negative cases in combination with only 50% preoperative knee aspirations and prevailing high failure rates confirm the need for improvement of diagnostic practice and treatment of infected knee arthroplasties.

Pancreatic ductal adenocarcinoma (PC) is characterized by a highly fibrotic desmoplastic stroma. Subtypes of cancer-associated fibroblasts (CAFs) have been identified in chemotherapy-naïve PC (CTN-PC), but their precise functions are still unclear. Our knowledge regarding the properties of CAFs in the regressive stroma after neoadjuvant treatment (NAT) of PC (NAT-PC) is particularly limited. We aimed to examine the marker phenotypic properties of CAFs in the regressive stroma of PC. Surgical specimens from patients with CTN-PC (n=10) and NAT-PC (n=10) were included. Juxtatumoural, peripheral, lobular, septal, peripancreatic, and regressive stromal compartments were manually outlined using digital imaging analysis (DIA) for area quantification. The compartment-specific expression of CD271, cytoglobin, DOG-1, miR-21, osteonectin, PDGF-Rβ, and tenascin C was evaluated by immunohistochemistry or in situ hybridization, using manual scoring and automated DIA. The area fraction of the regressive stroma was significantly higher in NAT-PC than in CTN-PC (P=0.0002). CD271 (P0.01), cytoglobin (P0.05), DOG1 (P0.05), miR-21 (P0.05), and tenascin C (P0.05) exhibited significant differences in their expression profiles between the juxtatumoural compared to the peripheral and regressive stroma. PDGF-Rβ expression was significantly higher in juxtatumoural than in peripheral CAFs (P0.05). Our data provide further support of the concept of stromal heterogeneity and phenotypic different CAF subtypes in PC. CAFs in the regressive stroma of NAT-PC show a marker phenotype similar to some (namely, peripheral) and different from other (namely, juxtatumoural) previously defined CAF subtypes. It may be hypothesized that phenotypic CAF subtypes, at least in part, also may share functional properties. Studies examining the precise functional characteristics of CAF subtypes in PC are needed.

Background Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients. Methods Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis. Results Myocellular infiltration of CD3−/CD8+ expressing natural killer cells increased following BFRE (P +/CD8− or CD3+/CD8+ T cells in BFRE or CON. CD3+/CD244+ T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68+/CD206−) and M2 anti-inflammatory (CD68+/CD206+) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups. Conclusions Low-load blood flow restriction exercise elicited an upregulation in CD3−/CD8+ expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.

Importance: Multimodal postoperative analgesia is widely used but lacks evidence of benefit.Objective: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens.Design, Setting, and Participants: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018.Interventions: Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery.Main Outcomes and Measures: Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P Results: Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P Conclusions and Relevance: Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia.Trial Registration: ClinicalTrials.gov Identifier: NCT02571361.

Objective:Saliva composition may affect sialolithiasis formation; thus, this study compared the salivary inorganic composition of sialolithiasis patients with that of healthy controls, and determined whether salivary inorganic composition changes after sialolithiasis surgery.Methods:The study included 40 patients with sialolithiasis and 40 matched healthy controls. Patients were examined before and after sialolithiasis surgery; controls were examined once. Flow rate and the inorganic saliva composition in unstimulated whole saliva were assessed.Results:Patients’ salivary flow prior to surgery was significantly lower compared to that of healthy controls, but equalised after surgery. Prior to surgery, patients’ saliva exhibited higher concentrations of calcium, magnesium, phosphorous compared to that of healthy controls. The concentration of most ions remained high after sialolithiasis surgery.Conclusion:Sialolithiasis patients had increased salivary concentrations of the ions that constitute the main inorganic phase of most sialoliths, and this may confer a risk for developing sialolithiasis.

The purpose of this study was to investigate the utility of postmortem computed tomography (PMCT) images in estimating organ sizes and to examine the use of the cardiothoracic ratio (CTR). We included 45 individuals (19 females), who underwent a medico-legal autopsy. Using the computer software program Mimics®, we determined in situ heart and liver volumes derived from linear measurements (width, height and depth) on a whole body PMCT-scan, and compared the volumes with ex vivo volumes derived by CT-scan of the eviscerated heart and liver. The ex vivo volumes were also compared with the organ weights. Further, we compared the CTR with the ex vivo heart volume and a heart weight-ratio (HWR). Intra- and inter-observer analyses were performed. We found no correlation between the in situ and ex vivo volumes of the heart and liver. However, a highly significant correlation was found between the ex vivo volumes and weights of the heart and liver. No correlations between CTR and the ex vivo heart volume nor with HWR was found. Concerning cardiomegaly, we found no agreement between the CTR and HWR. The intra- and inter-observer analyses showed no significant differences. Noninvasive in situ PMCT methods for organ measuring, as performed in this study, are not useful tools in forensic pathology. The best method to estimate organ volume is a CT-scan of the eviscerated organ. PMCT-determined CTR seems to be useless for ascertaining cardiomegaly, as it neither correlated with the ex vivo heart volume nor with the HWR.

Background: Arthrodesis is considered a salvage procedure after failure of a knee arthroplasty. Data on the use of this procedure are limited. The purpose of this study was to identify the incidence, causes, surgical techniques, and outcomes of arthrodesis after failed knee arthroplasty in a nationwide population. Methods: Data were extracted from the Danish Civil Registration System, the Danish National Patient Register, and the Danish Knee Arthroplasty Register. A total of 92,785 primary knee arthroplasties performed in Denmark from 1997 to 2013 were identified by linking the data using the unique personal identification number assigned to each patient. Of these arthroplasties, 165 were followed by arthrodesis. Hospital records of all identified cases of arthrodesis were reviewed. A competing risk model was used to estimate the cumulative incidence of arthrodesis in the study period. Differences in cumulative incidence were compared with the Gray test. Results: A total of 164 of the 165 arthrodeses were performed for causes related to failed knee arthroplasty. The 15-year cumulative incidence of arthrodesis was 0.26% (95% confidence interval, 0.21% to 0.31%). The 5-year cumulative incidence decreased significantly (p < 0.0001) from 0.32% for arthroplasties performed from 1997 to 2002 to 0.09% for arthroplasties performed from 2008 to 2013. The most common causes of arthrodesis were periprosthetic infection in 152 patients (93%), extensor mechanism disruption in 46 (28%), soft-tissue deficiency in 25 (15%), and severe bone loss in 11 (7%). In 79 patients (48%), there were 2 or more indications for arthrodesis. Solid fusion was achieved in 65% of the patients. The fusion rate was significantly higher after intramedullary nail fixation compared with external fixation (p = 0.01). A total of 34 patients (21%) underwent repeat arthrodesis, and 23 patients (14%) eventually underwent transfemoral amputation. Conclusions: The cumulative incidence of arthrodesis within 15 years after primary knee arthroplasty was 0.26%. There was a significant decrease in the 5-year cumulative incidence during the study period, suggesting an overall improvement in prevention of this adverse outcome of knee arthroplasty. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background and purpose - The surgical treatment of periprosthetic knee infection is generally either a partial revision procedure (open debridement and exchange of the tibial insert) or a 2-stage exchange arthroplasty procedure. We describe the failure rates of these procedures on a nationwide basis. Patients and methods - 105 partial revisions (100 patients) and 215 potential 2-stage revision procedures (205 patients) performed due to infection from July 1, 2011 to June 30, 2013 were identified from the Danish Knee Arthroplasty Register (DKR). Failure was defined as surgically related death ≤ 90 days postoperatively, re-revision due to infection, or not reaching the second stage for a planned 2-stage procedure within a median follow-up period of 3.2 (2.2-4.2) years. Results - The failure rate of the partial revisions was 43%. 71 of the partial revisions (67%) were revisions of a primary prosthesis with a re-revision rate due to infection of 34%, as compared to 55% in revisions of a revision prosthesis (p = 0.05). The failure rate of the 2-stage revisions was 30%. Median time interval between stages was 84 (9-597) days. 117 (54%) of the 2-stage revisions were revisions of a primary prosthesis with a re-revision rate due to infection of 21%, as compared to 29% in revisions of a previously revised prosthesis (p = 0.1). Overall postoperative mortality was 0.6% in high-volume centers (> 30 procedures within 2 years) as opposed to 7% in the remaining centers (p = 0.003). Interpretation - The failure rates of 43% after the partial revision procedures and 30% after the 2-stage revisions in combination with the higher mortality outside high-volume centers call for centralization and reconsideration of surgical strategies.

Temozolomide (TMZ) has recently been recommended as the first line chemotherapy in patients with aggressive pituitary tumors (APT) and pituitary carcinomas (PC) not controlled by standard treatment, i.e., surgery, radiotherapy and/or medical therapy (dopamine agonists, somatostatin analogs) [1]. About 40% of patients respond initially to TMZ, complete tumor regression is observed in

Background and purpose — Knee fracture treatment burden remains unknown, impeding proper use of hospital resources. We examined 20-year trends in incidence rates (IRs) and patient-, fracture-, and treatment-related characteristics of knee fracture patients. Patients and methods — This nationwide cohort study of prospectively collected data including patients with distal femoral, patellar, and proximal tibial fractures from the Danish National Patient Registry during 1998–2017, assesses IRs of knee fractures (per 105 inhabitants) as well as patient-, fracture-, and treatment-related characteristics of knee fracture patients. Results — During 1998–2017, 60,823 patients (median age 55; 57% female) sustained 74,106 knee fractures. 74% of the study population had a Charlson Comorbidity Index (CCI) of 0 and 18% a CCI of ≥ 2. 51% were proximal tibial fractures, 31% patellar fractures, and 18% distal femoral fractures. At the time of knee fracture, 20% patients had concomitant near-knee fractures (femur/tibia/fibula shaft/hip/ankle), 13% concomitant fractures (pelvic/spine/thorax/upper extremities), 5% osteoporosis, and 4% primary knee osteoarthritis. Over 1/3 knee fractures were surgically treated and of these 86% were open-reduction internal fixations, 9% external fixations, and 5% knee arthroplasties. The most common surgery type was proximal tibia plating (n = 4,868; 60% female). Knee fracture IR increased 12% to 70, females aged > 51 had the highest knee fracture IR, proximal tibial fracture had the highest knee fracture type IR (32) and surgically treated knee fracture IR increased 35% to 23. Interpretation — Knee fracture IRs, especially of surgically treated knee fractures, are increasing and proximal tibial fracture has the highest knee fracture type IR. Females aged > 51 and patients with comorbidity are associated with knee fracture, proximal tibial fracture, proximal tibial fracture surgery, and posttraumatic knee arthroplasty.

Background and purpose: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. Methods: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. Results: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. Conclusions: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

ObjectiveBacterial infection is a common finding in acute sialadenitis and may play a role in the chronicity of the condition. This study investigated if bacterial biofilm is present in submandibular chronic obstructive sialadenitis.MethodsA descriptive case–control study was conducted that compared 10 histological sections of submandibular glands with chronic obstructive sialadenitis, to 10 histological sections of the healthy part of submandibular glands with pleomorphic adenoma. Fluorescence in situ hybridisation and confocal laser scanning microscopy visualised evidence of bacterial biofilm.ResultsIn the chronic obstructive sialadenitis group, 5 out of 10 histological sections showed morphological evidence of bacterial biofilm. In the control group, there was no sign of bacterial biofilm formation.ConclusionMorphological evidence of bacterial biofilm was found in the submandibular gland sections from patients with chronic sialadenitis and suggests a role in the chronicity of submandibular chronic obstructive sialadenitis.

Background Physiotherapists (PTs) in primary health care manage patients with large variation in medical diagnosis, age, functional status, disability and prognosis. Lack of knowledge and systematically collected data from patients treated by PTs in primary health care has prompted this longitudinal observational physiotherapy project. This paper aims to describe a method for developing a database of patients managed by PTs in primary health care, with the main purpose to study patients’ characteristics, treatment courses and prognostic factors for favourable outcome. Methods This is a longitudinal observational project, following patients through their physiotherapy treatment periods in primary health care in Norway and until one year after inclusion. The project involves both private practitioners and municipally employed PTs working in primary health care in nine municipalities in Norway. The patients are recruited to three different cohorts depending on age and whether they are referred to a private practitioner or a municipally employed PT. All data are recorded electronically, transferred and stored securely. For all patients we have included extensive questionnaires to obtain information about demographics, disability and function, pain-related variables, psychosocial factors, treatments and evaluation of treatment as well as response to clinical tests. The PTs have access to use their own patients’ data. We have also prepared for linkage to national patient registers and data collected in population-based studies to be able to gather further important data. Discussion This project will have important implications for physiotherapy services in primary health care. The database contains more than 3000 patients, and data collection is ongoing. Data collected so far suggest that the patients included are representative of the larger population of patients treated by private practitioners or municipally employed PTs in Norway. This large scale prospective physiotherapy project will provide knowledge about the patient groups, applied treatments and short- and long-term outcome of the patients. Trial registration ClinicalTrials.gov Identifier: NCT03626389 . Registered on August 13th 2018 (retrospectively registered).

Background We aimed to investigate the impact of prolonged targeted temperature management (TTM) in cardiac arrest patients on release of serum levels of NSE and S-100b and their prognostic performances. Methods This is a substudy of the Targeted Temperature Management for 24 vs 48 h trial. NSE and S-100b levels were analysed retrospectively in serum samples collected upon admission, at 24, 48, and 72 h after reaching the target temperature of 33 ± 1 °C. The primary outcome was biomarker serum concentrations and secondary outcome was the cerebral performance category score after 6 months. Results 115 patients from two centres were analysed. NSE and S-100b levels did not differ between TTM groups at any single time-point. Poor outcome patients had higher biomarker levels at 24, 48, and 72 h: NSE: 9.73 (7.2; 10.9) versus 20.40 (12.7; 27.2), 8.86 (6.6; 9.6) versus 17.47 (11.1; 37.3) and 6.23 (5.3; 8.5) versus 31.05 (12.8; 52.5) respectively and S-100b: 0.09 (0.07; 0.11) versus 0.23 (0.19; 0.39), 0.08 (0.07; 0.09) versus 0.18 (0.15; 0.33) and 0.07 (0.06; 0.08) versus 0.13 (0.09; 0.23). The daily changes in NSE from admission to Day 2 after the cardiac arrest (CA) were also related to the outcome (p = 0.003 and p = 0.02). The best prediction of outcome was found at 72 h for NSE and at 24 h as well as 48 h for S100b. Conclusions No clinically relevant differences were found in the levels of NSE or S-100b between standard and prolonged TTM. Prognostic reliability of NSE and S-100b was unaltered by prolonged TTM.

Background High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu nicompartmental knee arthroplasty in the Nordic countries. Methods: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). Results: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. Conclusion: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals. publishedVersion

Background Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD). Method CD45+ CD34+ CD11b+ (7-AAD− CD3− CD19− CD294−) cells were isolated by cell sorting and stained for pro-collagen type 1. Thirty-nine patients (10 RA, 9 ILD and 10 with severe asthma, 10 with RA-ILD) and 10 healthy controls (HC) were included. Current medication, disease activity, pulmonary function test and radiographic data were collected. Circulating fibrocytes were quantified by flow cytometry. Peripheral blood mononuclear cells were isolated and cultured for 5 days and the numbers of mature fibrocytes were counted. Results 90.2% (mean, SD = 1.5%) of the sorted cells were pro-collagen type 1 positive and thereby fulfilled the criteria for being circulating fibrocytes. The ILD and RA-ILD groups had increased levels of circulating fibrocytes compared to HC (p

OBJECTIVES: Post-cardiotomy delirium is common and associated with increased morbidity and mortality. No gold standard exists for detecting delirium, and evidence to support the choice of treatment is needed. Haloperidol is widely used for treating delirium, but indication, doses and therapeutic targets vary. Moreover, doubt has been raised regarding overall efficacy. The purpose of this study was to assess the effect of a combination of early detection and standardized treatment with haloperidol on post-cardiotomy delirium, with the hypothesis that the proportion of delirium- and coma-free days could be increased. Length of stay (LOS), complications and 180-day mortality are reported. METHODS: Prospective interventional cohort study. One hundred and seventeen adult patients undergoing cardiac surgery were included before introduction of a screening and treatment protocol with haloperidol for delirium, and 123 patients were included after. Nurses screened patients using validated tools (the Delirium Observation Screening (DOS) scale and confusion assessment method for the intensive care unit (CAM-ICU)). In case of delirium, a checklist to eliminate precipitating/ inducing factors and a protocol for standardized dosing with haloperidol was applied. Group comparison was done using non-parametric tests and analysis of fractions, and associations between delirium and predefined covariates were analysed with logistic regression. RESULTS: Incidence of delirium after cardiac surgery was 21 (14–29) and 22 (15–30) %, onset was on postoperative day 1 (1–4) and 1 (1–3), duration was 1 (1–4) day and 3 (1–5) days, respectively, with no significant difference (Period 1 vs 2, all values are given as the median and 95% confidence interval). The proportion of delirium- and coma-free days was 67 (61–73) and 65 (60–70) %, respectively (ns). There was no difference in LOS or complication rate. Delirium was associated to increasing age, increased length of stay and complications. CONCLUSIONS: We observed no increase in the proportion of delirium- and coma-free days after introduction of a combination of early detection and standardized treatment with haloperidol on post-cardiotomy delirium. Most patients were not severely affected, and the few who were, proved difficult to treat, indicating that a simple treatment protocol with haloperidol was ineffective.

Background and purpose - The annual number of total knee arthroplasties (TKAs) has increased worldwide in recent years. To make projections regarding future needs for primaries and revisions, additional knowledge is important. We analyzed and compared the incidences among 4 Nordic countries Patients and methods - Using Nordic Arthroplasty Register Association (NARA) data from 4 countries, we analyzed differences between age and sex groups. We included patients over 30 years of age who were operated with TKA or unicompartmental knee arthroplasty (UKA) during the period 1997-2012. The negative binomial regression model was used to analyze changes in general trends and in sex and age groups. Results - The average annual increase in the incidence of TKA was statistically significant in all countries. The incidence of TKA was higher in women than in men in all 4 countries. It was highest in Finland in patients aged 65 years or more. At the end of the study period in 2012, Finland's total incidence was double that of Norway, 1.3 times that of Sweden and 1.4 times that of Denmark. The incidence was lowest in the youngest age groups (65 years) in all 4 countries. The proportional increase in incidence was highest in patients who were younger than 65 years. Interpretation - The incidence of knee arthroplasty steadily increased in the 4 countries over the study period. The differences between the countries were considerable, with the highest incidence in Finland. Patients aged 65 years or more contributed to most of the total incidence of knee arthroplasty.

Background Transfemoral amputation is considered the last treatment option for failed knee arthroplasty. The extent to which this procedure is performed is not well known. The purpose of this study was to identify the incidence and causes of amputation following failure of knee arthroplasty in a nationwide population. Methods Data were extracted from the Danish Civil Registration System, the Danish National Patient Register, and the Danish Knee Arthroplasty Register. With use of individual data linkage, 92,785 primary knee arthroplasties performed from 1997 to 2013 were identified. Of these, 258 were followed by amputation. Hospital records of all identified cases were reviewed. A competing-risk model was used to estimate the cumulative incidence of amputation. Differences in cumulative incidences were analyzed with use of the Gray test. Results A total of 115 amputations were performed for causes related to failed knee arthroplasty. The 15-year cumulative incidence of amputation was 0.32% (95% confidence interval [CI], 0.23% to 0.48%). The annual incidence of amputation following arthroplasties performed from 1997 to 2002 was 0.025% compared with 0.018% following arthroplasties performed from 2008 to 2013 (p = 0.06). The causes of the amputation were periprosthetic infection in 95 cases (83%), soft-tissue deficiency in 26 (23%), severe bone loss in 21 (18%), extensor mechanism disruption in 11 (10%), intractable pain in 11 (10%), periprosthetic fracture in 10 (9%), and vascular complications in 9 (8%). In 92 (80%) of the cases, there were ≥2 indications for amputation. Conclusions The cumulative incidence of amputation within 15 years after primary knee arthroplasty was 0.32%, with a tendency toward a decreasing incidence in the last part of the study period. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sialolithiasis is a frequent disorder affecting the salivary glands. The incidence rate (IR) has been reported to be 2.9-5.5 per 100,000 person-years, but all previous studies have been based on selected hospital data. In this study, we conducted a population-based study evaluating the IR of sialolithiasis and the IR variation according to age, gender and geography in Denmark. We included data from hospitals as well as from private ear, nose and throat (ENT) clinics. The study was based on registry data on all sialolithiasis cases in Denmark between 2003 and 2009 extracted from the Danish National Patient Registry (hospital cohort) and the Danish Regions Centre for Healthcare Statistics (private ENT clinic cohort). To validate the diagnosis, the proportion of visually confirmed cases was estimated based on patient records from subsamples of the two cohorts. The IR was 7.27 and 14.10 per 100,000 person-years based on visually confirmed cases only and on all cases, respectively. The highest IR was observed among 60- to 70-year-olds, in the North Denmark region and among females. In the validation subsamples, 35% of assumed sialoliths were visually confirmed in the private ENT clinic cohort and 59% in the hospital cohort. In this first population-based study of IR on sialolithiasis, we found a substantially higher IR. With respect to both visually confirmed cases and all cases, this is higher than previously reported from studies based on selected hospital data.

Background The fixation of uncemented tibia components in total knee arthroplasty may rely on the bone quality of the tibia; however, no previous studies have shown convincing objective proof of this. Component migration is relevant as it has been shown to predict aseptic loosening. Methods We performed 2-year follow-up of 92 patients who underwent total knee arthroplasty surgery with an uncemented tibia component. Bone mineral density (BMD; g/cm 2 ) of the tibia host bone was measured preoperatively using dual energy X-ray absorptiometry. The proximal tibia was divided into 2 regions of interest (ROI) in the part of the tibia bone where the components were implanted. Radiostereometric analysis was performed postoperatively and after 3, 6, 12, and 24 months. The primary outcome was maximum total point motion (MTPM; mm). Regression analysis was performed to evaluate the relation between preoperative BMD and MTPM. Results We found low preoperative BMD in ROI1 to be significantly related to high MTPM at all follow-ups: after 3 months (R 2 = 20%, P BMD = 0.017), 6 months (R 2 = 29%, P BMD = 0.003), 12 months (R 2 = 33%, P BMD = 0.001), and 24 months (R 2 = 27%, P BMD = 0.001). We also found a significant relation for low BMD in ROI2 and high MTPM: 3 months (R 2 = 19%, P BMD = 0.042), 6 months (R 2 = 28%, P BMD = 0.04), 12 months (R 2 = 32%, P BMD = 0.004), and 24 months (R 2 = 24%, P BMD = 0.005). Conclusion Low preoperative BMD in the tibia is related to high MTPM. Thus, high migration of uncemented tibia components is to be expected in patients with poor bone quality.

Introduction: Revision total knee arthroplasty with a cementless metaphyseal sleeve is suggested to be used without stem in revision total knee arthroplasty (rTKA). To the best of our knowledge, no papers investigating this have been published. The purpose of this study was to evaluate clinical outcome. Method: In this retrospective study, 71 patients operated with rTKA with sleeves without stem in the period 2009–2011 were identified; 63 were examined. All patients with the prosthesis still in place were invited to a medical examination including X-rays. American Knee Society Score (AKSS) and Oxford Knee Score (OKS) were used as primary clinical outcome scores. Results: Mean number of revisions including the revision with sleeve was 1.7. AKSS increased significantly from 62.7 to 109.6; (p value

Background and purpose — The surgical treatment of periprosthetic knee infection is generally either a partial revision procedure (open debridement and exchange of the tibial insert) or a 2-stage exchange arthroplasty procedure. We describe the failure rates of these procedures on a nationwide basis. Patients and methods — 105 partial revisions (100 patients) and 215 potential 2-stage revision procedures (205 patients) performed due to infection from July 1, 2011 to June 30, 2013 were identified from the Danish Knee Arthroplasty Register (DKR). Failure was defined as surgically related death ≤ 90 days postoperatively, re-revision due to infection, or not reaching the second stage for a planned 2-stage procedure within a median follow-up period of 3.2 (2.2–4.2) years. Results — The failure rate of the partial revisions was 43%. 71 of the partial revisions (67%) were revisions of a primary prosthesis with a re-revision rate due to infection of 34%, as compared to 55% in revisions of a revision prosthesis (p = 0.05). The failure rate of the 2-stage revisions was 30%. Median time interval between stages was 84 (9–597) days. 117 (54%) of the 2-stage revisions were revisions of a primary prosthesis with a re-revision rate due to infection of 21%, as compared to 29% in revisions of a previously revised prosthesis (p = 0.1). Overall postoperative mortality was 0.6% in high-volume centers (> 30 procedures within 2 years) as opposed to 7% in the remaining centers (p = 0.003). Interpretation — The failure rates of 43% after the partial revision procedures and 30% after the 2-stage revisions in combination with the higher mortality outside high-volume centers call for centralization and reconsideration of surgical strategies.

Background Regenerex is a novel porous titanium construct with a three-dimensional porous structure and biomechanical characteristics close to that of normal trabecular bone. The aim of this study was to compare this novel construct to a well-proven porous plasma sprayed tibial (PPS) implant after total knee arthroplasty. Methods Sixty-one patients scheduled for an uncemented TKA were randomized to receive either a novel highly porous titanium construct Regenerex or the PPS tibial component. Radiostereometric analysis of the tibial components was performed postoperatively and at three, six, 12, and 24months with measurements of migration (segment motion and maximum total point motion (MTPM)). Results Knee and function scores improved significantly from preoperatively to two-year follow-up. For both the Regenerex and the PPS the majority of migration appeared during the first three months and then stabilized. No statistically significant differences in MTPM were found in any follow-up between three and 24months. The Regenerex group had a lower migration rate between 12 and 24months compared with the PPS implants (p=0.03) but the PPS group had an initial significantly lower subsidence (p=0.04). Conclusion In conclusion the Regenerex implant could prove an effective scaffold material for coating of uncemented implants but did no better than the PPS component at 24months of follow-up. ClinicalTrials.gov identifier: NCT01936415.

Published online before print September 2010 Previous studies have shown that skeletal muscle glycogen and mitochondria are distributed in distinct subcellular localizations, but the role and regulation of these subcellular localizations are unclear. In the present study, we used transmission electron microscopy to investigate the effect of disuse and aging on human skeletal muscle glycogen and mitochondria content in subsarcolemmal (SS), intermyofibrillar (IMF), and intramyofibrillar (intra) localizations. Five young (∼23 yr) and five old (∼66 yr) recreationally active men had their quadriceps muscle immobilized for 2 wk by whole leg casting. Biopsies were obtained from m. vastus lateralis before and after the immobilization period. Immobilization induced a decrement of intra glycogen content by 54% (P

Objective Despite most patients with single-sided deafness (SSD) after operation for acoustic neuroma (AN) perceiving a significant hearing handicap, less than 25% are interested in bone-anchored hearing aid (BAHA) implantation. We evaluated the treatment compliance of BAHA in SSD and the effect of BAHA on the subjective handicap. Methods Part 1: It was determined, from our first study, how many of the SDD patients after operation for AN (n = 59) and interested in BAHA (n = 14) had been implanted. Part 2: Of 23 BAHA-implanted patients with SSD due to various causes, including the implanted patients from the previous study, 21 answered a questionnaire on the BAHA treatment compliance and the subjective handicap with and without BAHA. Results Part 1: Of the 14 patients from our first study who were interested in implantation for BAHA, 11 had been implanted (18.6% of all 59 patients). Part 2: Of the 21 patients with SSD, 95% still used BAHA, and of these, 81% used it more than 8 hours a day. Of the patients, 90% considered BAHA a moderate to significant aid; it reduced the subjective hearing handicap from 7.4 to 2.3 arbitrary units on a visual analog scale. Conclusion Despite the subjective handicap perception among most patients with SSD after AN surgery, less than 20% chose treatment with BAHA. Conversely, patients with SSD choosing implantation had high treatment compliance and felt that BAHA reduced their handicap. Thus, when selected by the patients after testing, BAHA is effective in SSD and results in a high patient compliance.

Electron microscopy revealed the presence of a 600-1500 A thick layer of polysaccharide on the surface of human corneal endothelial cells. The surface layer was visualized by combined fixation and staining in a mixture of ruthenium red and osmium tetroxide. The coating material was stable for at least 39 h post mortem and was retained on disintegrating cells.

Udgivelsesdato: Jul-9 The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical expression of CD133 in paraffin sections was analysed using morphometry. In all grades, CD133 was expressed on tumour and endothelial cells. Tumour cells were found in perivascular niches, as dispersed single cells and in pseudopalisade formations around necrosis. There was no correlation between the mean volume fraction of CD133(+) niches and all CD133(+) tumour cells and tumour grade. However, the volume fraction of CD133(+) blood vessels increased significantly from 0.4% in diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to patient survival. Double immunofluorescence stainings showed that the CD133(+) niches both contained CD133(+) cells with and without co-expression of the intermediate filament protein marker nestin, and only few CD133(+)/MIB-1(+) proliferating cells were found. In conclusion, a CD133(+) perivascular stem cell-like entity exists in astrocytomas. CD133(+) tumour vessels may play an important role in a brain tumour stem cell context, while CD133 alone does not appear to be a specific tumour stem cell marker related to patient survival.

Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting.

Regenerex is a novel porous titanium construct with a three-dimensional porous structure and biomechanical characteristics close to that of normal trabecular bone. The aim of this study was to evaluate the adaptive bone remodeling of the proximal tibia after uncemented total knee arthroplasty (TKA) using a tibial tray with this novel coating compared to a well-proven standard porous coated (PPS) tibial tray. Sixty patients scheduled for TKA were randomized to receive either a Regenerex (n = 31) or a PPS tibial component (n = 29). Changes in bone mineral density (BMD) of the proximal tibia were measured at three, six, 12 and 24 months by dual-energy X-ray absorptiometry (DEXA). In the lateral region (ROI 3), a significant increase in BMD was seen in both groups at three, six, and 12 months after surgery. The relative increase at 12 months was 8.1 % (P = 0.007) for the PPS group and 6.5 % (P = 0.002) for the Regenerex group. Positive values were retained at 24 months in both groups. At 24 months BMD in the distal region below the central stem (ROI 1) had decreased in the PPS group by 3.4 % (P = 0.005) and in the Regenerex group by 2.4 % (P = 0.17). In the medial region (ROI 2) BMD remained unchanged at all follow-up evaluations in both groups. There were no significant differences between the two groups (P = 0.45) in any ROI at any follow-up evaluation. The significant increase in BMD of the lateral proximal tibia plateau with very limited changes medially and distally seen in both implants suggests that the novel porous titanium construct Regenerex and the PPS implant have a pronounced beneficial effect with regard to maintaining periprosthetic BMD in all regions of interest investigated.

Objective: To evaluate the subjective hearing handicap in patients with unilateral deafness after acoustic neuroma surgery and the effect of the Bone-anchored Hearing Aid (BAHA) on test band. Study Design: Fifty-nine consecutive patients with unilateral deafness after translabyrintine removal of an acoustic neuroma, treated in Denmark in 2001 and 2002, were included. The patients were asked to complete a questionnaire, which addressed the subjective handicap of unilateral deafness; 90% responded. These patients were invited to test the BAHA on test band, and the subjective and objective effects were recorded. Results: Eighty percent of the patients thought that they had a subjective hearing handicap of some significance. However, only 50% accepted the invitation to test the BAHA. The overall subjective effect was positive, and a significant improvement in speech discrimination in noise with the BAHA was demonstrated. After the test, however, only about 50%, that is, 25% of all patients wished implantation for BAHA treatment. Conclusion: This study shows that unilateral deafness after acoustic neuroma surgery is thought as a handicap in most of the patients and confirms that treatment with the BAHA has positive subjective effects and improves speech discrimination in noise. However, only 25% of the patients wished implantation for BAHA treatment. The implications of these findings are discussed. Data from centers that perform simultaneous acoustic neuroma surgery and implantation for BAHA are necessary for firm conclusions.

The outcome of performing isolated tibial polyethylene insert exchange (ITPIE) after total knee arthroplasty (TKA) is under debate. We evaluated the survival probability of ITPE after uncemented TKA.27 patients (27 knees) with an ITPIE performed mean 9 (0.9-17) years after the initial TKA were included in the study (22 patients also had the patellar component replaced simultaneously). All patients had their exchange performed at our department between 1997 and 2001 and had their latest follow-up examination mean 40 (8-71) months after the exchange.During the follow-up, 2 patients had total knee revision because of aseptic loosening and 2 patients had isolated patella component exchange (in 1 of the patients, combined with a new ITPIE). Kaplan-Meier survival analysis gave a survival probability of 80% at 34 months of follow-up.The short-term survival after an ITPIE was similar to that of a total knee revision with exchange of all components. Since the ITPIE is a much smaller operation with fast rehabilitation, we recommend it in elderly patients with a well-fixed and wellaligned prosthesis without surface damage of the components.

Udgivelsesdato: 2004-Apr Nine novel sugar transporter-like proteins have been discovered in the past 5 years. The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11 and GLUT12, have been detected in human skeletal muscle. In the present study, we examined the pattern of expression and localization of the GLUT isoforms 8, 11 and 12 in human skeletal muscle using an immunohistochemical approach. Biopsies of human skeletal muscle from sedentary or trained healthy adults, from fetal muscle (24 weeks of gestation), from obese type-2 diabetic subjects, and from patients suffering from polymyositis or amyotrophic lateral sclerosis (ALS) were studied. GLUT8 and 12 immunoreactivity was below detection level in both developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast, GLUT4 was expressed in all investigated muscle fibres, the pattern of expression of GLUT11 differs from that of GLUT4, suggesting a specialized function for GLUT11 with a regulation independent from that of GLUT4. Obesity, type-2 diabetes, training, conditions of de- and reinnervation (ALS) and regeneration (polymyositis) failed to induce GLUT8 or -12 expression. Likewise, the fibre type-dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed exclusively in slow-twitch muscle fibres and is unaffected by physiological and pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not appear to be of importance in human muscle under physiological and pathophysiological conditions.