The "true" 1-year incidence of dislocation after primary total hip arthroplasty: validation of an algorithm identifying dislocations in the Danish National Patient Register based on 5,415 patients from the Danish Hip Arthroplasty Register.

BACKGROUND AND PURPOSE: Dislocations continue to be a serious complication after primary total hip arthroplasty (THA). Our primary aim was to report the "true" incidence of dislocations in Denmark and secondarily to validate a previously developed algorithm designed to identify THA dislocations in the updated version of the Danish National Patient Register (DNPR), based on data from the Danish Hip Arthroplasty Register (DHR). METHODS: We included 5,415 primary THAs from the DHR performed from July 1 to December 31, 2019. Version 3 of the DNPR was launched in February 2019, and a combination of data from the DNPR and a comprehensive national review of 1,762 hospital contacts enabled us to identify every dislocation occurring during the 1st year after THA to determine the "true" 1-year incidence of dislocation. The results were presented as proportions with 95% confidence intervals (CI), and validation was performed by calculating sensitivity and predictive values. RESULTS: The "true" 1-year incidence of dislocation was 2.8% (CI 2.4-3.3). Of these, 37% suffered recurrent dislocations during the follow-up period. Between-hospital variation ranged from 0.0% to 9.6%. The algorithm demonstrated a sensitivity close to 95%, while maintaining a positive predictive value of above 94%. CONCLUSION:  The "true" 1-year incidence of dislocation of 2.8% is comparable to earlier findings, and large variation among hospitals continues to be evident. We have proven the algorithm to be valid in the latest DNPR (version 3), enabling it to be employed as a new quality indicator in future annual DHR reports.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.

Citrullination of myelin basic protein induces a Th17-cell response in healthy individuals and enhances the presentation of MBP85-99 in patients with multiple sclerosis.

The post-translational modification citrullination has been proposed to play a role in the pathogenesis of multiple sclerosis (MS). Myelin basic protein (MBP) is a candidate autoantigen which is citrullinated to a minor extent under physiological conditions and hypercitrullinated in MS. We examined immune cell responses elicited by hypercitrullinated MBP (citMBP) in cultures of mononuclear cells from 18 patients with MS and 42 healthy donors (HDs). The immunodominant peptide of MBP, MBP85-99, containing citrulline in position 99, outcompeted the binding of native MBP85-99 to HLA-DR15, which is strongly linked to MS. Moreover, using the monoclonal antibody MK16 as probe, we observed that B cells and monocytes from HLA-DR15+ patients with MS presented MBP85-99 more efficiently after challenge with citMBP than with native MBP. Both citMBP and native MBP induced proliferation of CD4+ T cells from patients with MS as well as TNF-α production by their B cells and CD4+ T cells, and citrullination of MBP tended to enhance TNF-α secretion by CD4+ T cells from HLA-DR15+ patients. Unlike native MBP, citMBP induced differentiation into Th17 cells in cultures from HDs, while neither form of MBP induced Th17-cell differentiation in cultures from patients with MS. These data suggest a role for citrullination in the breach of tolerance to MBP in healthy individuals and in maintenance of the autoimmune response to MBP in patients with MS.

Do Dual-mobility Cups Reduce Revision Risk in Femoral Neck Fractures Compared With Conventional THA Designs? An International Meta-analysis of Arthroplasty Registries.

BACKGROUND: Dual-mobility cups in THA were designed to reduce prosthesis instability and the subsequent risk of revision surgery in high-risk patients, such as those with hip fractures. However, there are limited data from clinical studies reporting a revision benefit of dual-mobility over conventional THA. Collaboration between anthroplasty registries provides an opportunity to describe international practice variation and compare between-country, all-cause revision rates for dual-mobility and conventional THA. QUESTIONS/PURPOSES: We summarized observational data from multiple arthroplasty registries for patients receiving either a dual-mobility or conventional THA to ask: (1) Is dual-mobility use associated with a difference in risk of all-cause revision surgery compared with conventional THA? (2) Are there specific patient characteristics associated with dual-mobility use in the hip fracture population? (3) Has the use of dual-mobility constructs changed over time in patients receiving a THA for hip fracture? METHODS: Six member registries of the International Society of Arthroplasty Registries (from Australia, Denmark, Sweden, the Netherlands, the United Kingdom, and the United States) provided custom aggregate data reports stratified by acetabular cup type (dual-mobility or conventional THA) in primary THA for hip fracture between January 1, 2002, and December 31, 2019; surgical approach; and patient demographic data (sex, mean age, American Society of Anesthesiologists class, and BMI). The cumulative percent revision and mortality were calculated for each registry. To determine a global hazard ratio of all-cause revision for dual-mobility compared with conventional THA designs, we used a pseudoindividual patient data approach to pool Kaplan-Meier prosthesis revision data from each registry and perform a meta-analysis. The pseudoindividual patient data approach is a validated technique for meta-analysis of aggregate time-to-event survival data, such as revision surgery, from multiple sources. Data were available for 15,024 dual-mobility THAs and 97,200 conventional THAs performed for hip fractures during the study period. RESULTS: After pooling of complete Kaplan-Meier survival data from all six registries, the cumulative percent revision for conventional THA was 4.3% (95% confidence interval [CI] 4.2% to 4.5%) and 4.7% (95% CI 4.3% to 5.3%) for dual-mobility THA at 5 years. We did not demonstrate a lower risk of all-cause revision for patients receiving dual-mobility over conventional THA designs for hip fracture in the meta-analysis once between-registry differences were adjusted for (HR 0.96 [95% CI 0.86 to 1.06]). A lower proportion of dual-mobility procedures were revised for dislocation than conventional THAs (0.9% versus 1.4%) but a higher proportion were revised for infection (1.2% versus 0.8%). In most registries, a greater proportion of dual-mobility THA patients were older, had more comorbidities, and underwent a posterior approach compared with conventional THA (p < 0.001). The proportion of dual-mobility THA used to treat hip fractures increased in each registry over time and constituted 21% (2438 of 11,874) of all THA procedures in 2019. CONCLUSION: The proportion of dual-mobility THAs in patients with hip fractures increased over time, but there was large variation in use across countries represented here. Dual-mobility cups were not associated with a reduction in the overall risk of revision surgery in patients with hip fractures. A randomized controlled trial powered to detect the incidence of dislocation and subsequent revision surgery is required to clarify the efficacy of dual-mobility cups to treat hip fractures. LEVEL OF EVIDENCE: Level III, therapeutic study.

Migraine with aura in women is not associated with structural thalamic abnormalities.

Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent. Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified from the Danish Twin Registry. We used two advanced, validated analysis methods to assess the volume of the thalamus and its nuclei; the MAGeT Brain Algorithm and a recently developed FreeSurfer-based method based on a probabilistic atlas of the thalamic nuclei combining ex vivo MRI and histology. These approaches were very similar to the methods used in each of the two previous studies. Between-group comparisons were corrected for potential effects of age, educational level, BMI, smoking, alcohol, and hypertension using a linear mixed model. Further, we used linear mixed models and visual inspection of data to assess relations between migraine aura frequency and thalamic nuclei volumes in patients. In addition, we performed paired t-tests to compare volumes of twin pairs (N = 29) discordant for migraine with aura. None of our analyses showed any between-group differences in volume of the thalamus or of individual thalamic nuclei. Our results indicate that the pathophysiology of migraine with aura does not involve alteration of thalamic volume.

Global brain atrophy and metabolic dysfunction in LGI1 encephalitis: A prospective multimodal MRI study.

BACKGROUND: Chronic cognitive deficits are frequent in leucin-rich glioma-inactivated 1 protein (LGI1) encephalitis. We examined structural and metabolic brain abnormalities following LGI1 encephalitis and correlated findings with acute and follow-up clinical outcomes. METHODS: Nine patients underwent prospective multimodal 3 Tesla MRI 33.1±18months after disease onset, including automated volumetry, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Data were compared to 9 age- and sex-matched healthy controls. RESULTS: Although extratemporal lesions were not present on MRI in the acute stage, tract-based spatial statistics analyses of DTI during follow-up showed widespread changes in the cerebral and cerebellar white matter (WM), most prominent in the anterior parts of the corona radiata, capsula interna and corpus callosum. MRS revealed lower glutamine/glutamate WM levels compared to controls. Higher cerebellar gray matter volume was associated with better function at disease onset (measured by the modified Rankin Scale), and higher putaminal volume was associated with better cognition by Addenbrooke's Cognitive Examination test at 23.4±7.6months. CONCLUSIONS: Poor clinical outcome following LGI1 encephalitis is associated with global brain atrophy and disintegration of white matter tracts. The pathological changes affect not only temporomesial structures but also frontal lobes and the cerebellum.

The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients.

Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common genetic disease. Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to eradicate; the resulting chronic infections are associated with severe declines in lung function and increased mortality rates. B. cenocepacia strain J2315 was isolated from a CF patient and is a member of the epidemic ET12 lineage that originated in Canada or the United Kingdom and spread to Europe. The 8.06-Mb genome of this highly transmissible pathogen comprises three circular chromosomes and a plasmid and encodes a broad array of functions typical of this metabolically versatile genus, as well as numerous virulence and drug resistance functions. Although B. cenocepacia strains can be isolated from soil and can be pathogenic to both plants and man, J2315 is representative of a lineage of B. cenocepacia rarely isolated from the environment and which spreads between CF patients. Comparative analysis revealed that ca. 21% of the genome is unique in comparison to other strains of B. cenocepacia, highlighting the genomic plasticity of this species. Pseudogenes in virulence determinants suggest that the pathogenic response of J2315 may have been recently selected to promote persistence in the CF lung. The J2315 genome contains evidence that its unique and highly adapted genetic content has played a significant role in its success as an epidemic CF pathogen.