Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Ankle fusion after failed ankle replacement in rheumatic and non-rheumatic patients

Background: With longer follow-up, survival rate of total ankle replacements (TAR) diminishes. It is therefore important to have a reliable fall-back option in case of failed TAR. Revision arthroplasty is often impossible because of loss of bonestock or infection. Conversion to ankle fusion is then indicated. We investigated the clinical, radiographic and patient reported results for fusion after failed TAR in a consecutive group of patients. We concentrated on the influence of inflammatory joint disease (IJD) on union rate. Methods: Patient files and radiographic images of 46 consecutive patients (47 ankles) were reviewed. There were 22 patients with IJD. Fixation methods included; anterior plating, blade plate fixation, intramedullary nailing, compression screws and external fixation. Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM) were used to determine patient related outcomes. Results: Forty out of 47 ankles (85%) Fused. Union rate in the non-IJD group (96%) was significantly higher compared to the IJD-group (73%, p = 0.04). Revisions and complications were more frequent in the IJD group, but numbers were too small to detect a significant difference. Mean PROM scores were: FAOS-symptoms; 68.5, FAOS-pain; 70.3, FAOS-QoL; 43.7, FAOS-ADL; 68.1 and FAAM-ADL; 52.1, with no significant difference between IJD and non-IJD patients. Conclusions: IJD-patients have a higher nonunion rate after ankle fusion for failed TAR. However, patient reported outcome is not significantly different between the two groups. Level of evidence: IV, retrospective cohort

The diagnosis and treatment of isolated type B fibular fractures: Results of a nationwide survey

Introduction: In isolated Weber B fractures (type B fibular fractures), ruling out instability is critical for safe conservative treatment. In fractures without evident medial injury, additional diagnostics like MRI scan or gravity stress test should be done to differentiate between a stable and unstable fracture. The aim of the current study is to gain more insight in current practice and treatment of type B fractures by Dutch trauma- and orthopaedic surgeons. Materials & methods: In December 2017 and January 2018, 559 trauma surgeons were invited by email to join an online survey. This survey consisted of questions regarding diagnostics and treatment of isolated distal fibula fractures. Also, respondents were asked to state their preferred treatment of eight separate cases. Results: In total, 161 surgeons participated, covering 68 different hospitals in the Netherlands. Of them, 32.0% treat more than 30 ankle fractures a year. Based on regular mortise radiographs, 13.6% of the respondents chose surgical treatment in case of a medial clear space (MCS) > 4 mm, 33.8% in case of a MCS > 6 mm and 45.5% in case of a MCS > 4 mm in addition to the MCS ≥ superior clear space + 1 mm. Moreover, 18.2% make use of additional diagnostics (43.9% repeat mortise view after a week, 16.6% weight bearing radiograph, 8.6% gravity stress view, 7.9% exorotation radiograph, 6.5% MRI scan, 0.7% ultrasound, 16.8% other) and 8% establishes their decision not based on the mortise radiograph. Fibular dislocation of ≥ 2 mm was used as an indication for surgical treatment by 69%. Of them, 56% decides to treat surgically in these cases, even with proven medial stability. Conclusion: Many surgeons treat type B fibular fractures with a MCS > 4 mm at mortise view surgically, even without proven medial injury. Rarely, additional diagnostics as MRI or gravity stress test are performed in cases with a MCS 4–6 mm. Consequently many stable ankle fractures are treated operatively unnecessarily

Tension band wiring for simple olecranon fractures: evaluation of surgical technique

Background: In some settings, specific techniques for open reduction and internal fixation are preferred based on the eminence of a surgeon or professional organization. An emphasis on technical aspects of surgery that are not proved superior and vary substantially from surgeon to surgeon can be confusing for trainees. This study applied a numerical grading of the technical aspects of tension band wire (TBW) fixation for olecranon fracture; assessed the interobserver agreement of each criterion; and measured the correlation of the technical grading and objective and subjective long-term outcomes. Materials and methods Forty observers were invited to rate the technical aspects of TBW fixation of the olecranon on 26 post-operative radiographs. The interobserver reliability of the rating was measured using the intra-class correlation coefficient. The correlation between the rating and motion, Mayo elbow performance index, and disabilities of the arm, shoulder and hand score was tested with the Spearman’s rank correlation test. Results: None of the figure-of-eight TBW constructs were considered perfect according to the numerical grading: the majority of observers found three deviations per fixation. The interobserver agreement was only fair for the total number of deviations and no correlation between the number of deviations and long-term objective and subjective outcome was found. Conclusions: A rating of the technical aspects of TBW for olecranon fractures was unreliable and did not correlate with subjective and objective outcomes. Emphasis on specific technical aspects of fixation might be confusing for trainees and could distract them from the principles of effective treatment. Level of evidence Level IV diagnostic study

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Pathophysiology, epidemiology and therapy of agein