Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial.

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<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain. 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<0.001 between DX2 and placebo. Postoperative pain was reduced at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone. CONCLUSION: Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain. TRIAL REGISTRATION: Clinicaltrials.gov NCT03506789.

What Factors are Associated with Revision or Worse Patient-reported Outcome after Reverse Shoulder Arthroplasty for Cuff-tear Arthropathy? A Study from the Danish Shoulder Arthroplasty Registry.

BACKGROUND: Reverse shoulder arthroplasty has been proven to improve function in shoulders with cuff-tear arthropathy, but existing studies are primarily single-center studies with a small number of patients, which limits their ability to identify patients who have an increased risk of revision or a worse functional outcome. QUESTIONS/PURPOSES: (1) What is the estimated 10-year cumulative revision rate after reverse shoulder arthroplasty for cuff-tear arthropathy, and what factors are associated with the risk of revision? (2) What is the patient-reported outcome 1 year after surgery, and what factors are associated with a worse patient-reported outcome? METHODS: We included all patients treated with reverse shoulder arthroplasty for cuff-tear arthropathy reported in the Danish Shoulder Arthroplasty Registry from 2006 to 2015. During the study period, the completeness of reporting was 93% for both primary and revision arthroplasties. Estimated revision rates were illustrated using the Kaplan-Meier method, and hazard ratios were calculated using a Cox regression model. Patient-reported outcome was measured with a postal survey at 12 months (range 10-14 months) postoperatively using the Western Ontario Osteoarthritis of the Shoulder (WOOS) index. The WOOS is a patient-administered questionnaire that measures the quality of life of patients with glenohumeral osteoarthritis. A visual analog scale that ranges from 0 to 100 is used for each question. There are 19 questions, giving a total score ranging from 0 to 1900, with 1900 being the worst. For simplicity of presentation, raw scores were converted to a percentage of the maximum score, with 100 being the best. There is no defined minimal clinically important difference of the WOOS, but the Danish Shoulder arthroplasty registry has for many years regarded an arbitrary difference of 10 or above as being clinically relevant. The rate of response to the WOOS was 71%. RESULTS: The estimated 10-year cumulative revision rate was 8.5% (95% confidence interval, 5.7%-11.3%) with differences between the arthroplasty model (21.0%; 95% CI, 11.8% to 30.8% for the Delta Mark III and 5.5%; 95% CI, 3.7% to 7.3% for the Delta Xtend) and gender (6.0%; 95% CI, 3.0% to 9.0% for women and 13.1%; 95% CI, 7.1% to 19.1% for men). After controlling for potential confounding variables including gender, previous surgery, arthroplasty model, and period of surgery, the risk of revision was higher with the Delta Mark III than with the Delta Xtend (hazard ratio 2.7; 95% CI, 1.3 to 5.4; p < 0.01) and higher in men than in women (hazard ratio 2.7; 95% CI, 1.6 to 4.7; p < 0.01). Thirty-three percent (19 of 57) of the revision arthroplasties were performed for dislocation and 32% (18 of 57) were to treat periprosthetic joint infection. After controlling for confounding variables, only previous surgery was associated with a worse WOOS score (mean difference -10.6; 95% CI, -15.2 to -5.9; p < 0.01); there were no associations between a worse score and gender, arthroplasty model, age group, or period of surgery. CONCLUSIONS: The results from the present study can be used to inform patients about their individual risk of revision or a disappointing functional outcome. The study also demonstrates the need for proper patient selection and attention to technical details to reduce the risk of revision, especially for men. Our follow-up time was, however, short, with only an estimate of the 10-year revision rate. Future studies with a long-term follow-up duration are needed to confirm our results. LEVEL OF EVIDENCE: Level III, therapeutic study.

Poor patient-reported outcome after shoulder replacement in young patients with cuff-tear arthropathy: a matched-pair analysis from the Danish Shoulder Arthroplasty Registry.

Background and purpose - Reverse shoulder arthroplasty (RSA) has become the treatment of choice for cuff-tear arthropathy. There are, however, concerns about the longevity and the outcome of an eventual revision procedure. Thus, resurfacing hemiarthroplasty (RHA) with extended articular surface has been suggested for younger patients. We compared the patient-reported outcome of these arthroplasty designs for cuff-tear arthropathy. Patients and methods - We included patients operated on because of cuff-tear arthropathy and reported to the Danish Shoulder Arthroplasty Registry (DSR) from January 1, 2006 to December 31, 2013. 117 RHA cases were matched by age and sex with 233 RSA controls. 34 of the RHAs were conventional and 67 were RHAs with extended articular surface. The Western Ontario Osteoarthritis of the Shoulder (WOOS) Index at 1 year was used as primary outcome. The score was converted to a percentage of a maximum score. Revision, defined as removal or exchange of any component or the addition of a glenoid component, was used as secondary outcome. Results - Median WOOS was 49 (30-81) for RHA and 77 (50-92) for RSA (p < 0.001). For patients younger than 65 years, median WOOS was 58 (44-80) after RHA, similar to the 54 after RSA (37-85). For patients older than 65 years, median WOOS was 48 (28-82) after RHA and 79 (55-92) after RSA (p < 0.001). Interpretation - In all patients RSA had a clinically and statistically better patient-reported outcome than RHA. However, in patients younger than 65 years the functional outcome was similar and poor for either arthroplasty type. The optimal treatment of CTA in young patients remains a challenge.

ATG16L1: A multifunctional susceptibility factor in Crohn disease.

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.