Relation between smoking history and gene expression profiles in lung adenocarcinomas

Background: Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. Methods: Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. Results: Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. Conclusions: Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history

Accumulation of Self-Reactive Naive and Memory B Cell Reveals Sequential Defects in B Cell Tolerance Checkpoints in Sjogren's Syndrome

This work was funded by grants number 18237 and 20089 from Arthritis Research UK (http://www.arthritisresearchuk.org) to MB and the William Harvey Research Foundation. EC was recipient of short-term travel fellowships from EMBO (ASTF 318-2010) and EFIS-IL

Low risk of revision after reverse shoulder arthroplasty for acute proximal humeral fractures

Background: Reverse shoulder arthroplasty (RSA) has gained popularity in the treatment of proximal humeral fractures (PHFs), especially in elderly patients. The purpose of this study was to investigate the use of RSA implants for acute PHFs and risk of revision, as well as risk factors for revision.Methods: RSA implants for acute PHFs were identified from the Nordic Arthroplasty Register Association registry data from 2004 to 2016. Kaplan-Meier survival analysis was used to calculate implant survival. Cox multiple regression analysis was used to calculate the adjusted revision rate for sex, age, country of operation, and year of surgery.Results: The study included 1523 RSA implants for PHFs (84% women; average age, 77 years; average follow-up time, 2.5 years). The 5-year cumulative implant survival rate was 97% (confidence limits, 95.5% and 98%). Revision was performed for 33 implants (2%). The most common reason for revision was instability, occurring in 11 cases (0.7%), followed by fracture, occurring in 6 (0.4%), and infection, occurring in 5 (0.3%). Four different arthroplasty brands were used in this cohort, with the Delta Xtend in two-thirds of cases (n = 1025). Age younger than 60 years and male sex were associated with slightly higher rates of revision; however, these differences did not reach statistical significance (hazard ratio of 2.02 with P = .075 and hazard ratio of 3.23 with P = .057, respectively).Conclusion: The use of RSA for acute PHFs is increasing in the Nordic countries. The short-term risk of revision is low. The main reason for revision of RSA for this indication is instability.</p

Low arthroplasty survival after treatment for proximal humerus fracture sequelae: 3,245 shoulder replacements from the Nordic Arthroplasty Register Association

Background and purpose - Proximal humerus fractures (PHF) may result in sequelae indicating arthroplasty. We report cumulative survival rates and reasons for revision after arthroplasty for proximal humerus fracture sequelae (PHFS). Patients and methods - Data were derived from the Nordic Arthroplasty Register Association. The Kaplan-Meier method was used to illustrate survival rates. A scaled Schoenfeld residual plot was used to report the risk of revision for men relative to women in patients who were treated with reverse shoulder arthroplasty (RSA). Revision was defined as removal or exchange of any component or the addition of a glenoid component. Results - 30,190 primary arthroplasties were reported from 2004 to 2016, of which 3,245 were for PHFS. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 96% (95-97), 90% (89-92), and 86% (83-88) for stemmed hemiarthroplasty and 94% (92-95), 89% (87-91), and 86% (82-90) for RSA with a median time to revision of 18 months (IQR 9-44) and 3 months (IQR 0-17). The risk of revision for men relative to women in patients who were treated with RSA was 3.2 (1.9-5.1) 0-1 year after surgery and 1.9 (0.9-4.1) 1-8 years after surgery. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 94% (92-96), 88% (85-90), and 80% (75-86) for men and 95% (94-96), 86% (84-89), and 81% (77-84) for young patients. Interpretation - Shoulder arthroplasty for PHFS was associated with lower survival rates, compared with previously published results of shoulder arthroplasty for acute PHF. The low arthroplasty survival rates for men and young patients especially are worrying

The Nordic Arthroplasty Register Association: A unique collaboration between 3 national hip arthroplasty registries with 280,201 THRs

Background and purpose The possibility of comparing results and of pooling the data has been limited for the Nordic arthroplasty registries, because of different registration systems and questionnaires. We have established a common Nordic database, in order to compare demographics and the results of total hip replacement surgery between countries. In addition, we plan to study results in patient groups in which the numbers are too small to be studied in the individual countries

The Bankart repair versus the Putti-Platt procedure: A randomized study with WOSI score at 10-year follow-up in 62 patients

Background and purpose This randomized study compared clinical results after surgery for posttraumatic shoulder instability with either an anatomical repair or an older, less anatomical but commonly used method. The less anatomical procedure has been considered quicker and less demanding, but it has been questioned regarding the clinical result. We therefore wanted to compare the clinical outcome of the two different procedures. Our hypothesis was that the anatomical repair would give less residual impairment postoperatively

Treatment of glenohumeral instability in rugby players

Rugby is a high-impact collision sport, with impact forces. Shoulder injuries are common and result in the longest time off sport for any joint injury in rugby. The most common injuries are to the glenohumeral joint with varying degrees of instability. The degree of instability can guide management. The three main types of instability presentations are: (1) frank dislocation, (2) subluxations and (3) subclinical instability with pain and clicking. Understanding the exact mechanism of injury can guide diagnosis with classical patterns of structural injuries. The standard clinical examination in a large, muscular athlete may be normal, so specific tests and techniques are needed to unearth signs of pathology. Taking these factors into consideration, along with the imaging, allows a treatment strategy. However, patient and sport factors need to be also considered, particularly the time of the season and stage of sporting career. Surgery to repair the structural damage should include all lesions found. In chronic, recurrent dislocations with major structural lesions, reconstruction procedures such as the Latarjet procedure yields better outcomes. Rehabilitation should be safe, goal-driven and athlete- specific. Return to sport is dependent on a number of factors, driven by the healing process, sport requirements and extrinsic pressures

The benefits of collaboration: the Nordic Arthroplasty Register Association

The Nordic Arthroplasty Register Association (NARA) was established in 2007 by arthroplasty register representatives from Sweden, Norway and Denmark with the overall aim to improve the quality of research and thereby enhance the possibility for quality improvement with arthroplasty surgery. Finland joined the NARA collaboration in 2010.NARA minimal hip, knee and shoulder datasets were created with variables that all countries can deliver. They are dynamic datasets, currently with 25 variables for hip arthroplasty, 20 for knee arthroplasty and 20 for shoulder arthroplasty.NARA has published statistical guidelines for the analysis of arthroplasty register data. The association is continuously working on the improvement of statistical methods and the application of new ones.There are 31 published peer-reviewed papers based on the NARA databases and 20 ongoing projects in different phases. Several NARA publications have significantly affected clinical practice. For example, metal-on-metal total hip arthroplasty and resurfacing arthroplasty have been abandoned due to increased revision risk based on i.a. NARA reports. Further, the use of uncemented total hip arthroplasty in elderly patients has decreased significantly, especially in Finland, based on the NARA data.The NARA collaboration has been successful because the countries were able to agree on a common dataset and variable definitions. The collaboration was also successful because the group was able to initiate a number of research projects and provide answers to clinically relevant questions. A number of specific goals, set up in 2007, have been achieved and new one has emerged in the process