Significant variability exists in preoperative planning software measures of glenoid morphology for shoulder arthroplasty

Background & Hypothesis: We sought to assess the reliability of 4 different shoulder arthroplasty 3-dimensional preoperative planning programs. Comparison was also made to manual measurements conducted by 2 fellowship-trained musculoskeletal radiologists. We hypothesized that there would be significant variation in measurements of glenoid anatomy affected by glenoid deformity. Methods: A retrospective review of computed tomography (CT) scans of patients undergoing shoulder arthroplasty was undertaken. A total of 76 computed tomographies were analyzed for glenoid version and inclination by 4 templating software systems (VIP, Blueprint, TrueSight, ExactechGPS). Inter-rater reliability was assessed via intra-class correlation coefficient (ICC). For those shoulders with glenohumeral arthritis (58/76), ICC was also calculated when sub-grouping by modified Walch classification. Lin\u27s concordance correlation coefficient was calculated for each system with 2 musculoskeletal-trained radiologists’ measurements. Results: Measurements of glenoid version and inclination differed between at least 2 programs by 5º-10º in 75% and 92% of glenoids respectively, and by \u3e10º in 18% and 45% respectively. ICC was excellent for version but only moderate for inclination. ICC was highest among Walch A glenoids for both version (near excellent) and inclination (good), and lowest among Walch D for version (near poor) and Walch B for inclination (moderate). When measuring version, VIP had the highest concordance with manual measurement; Blueprint had the lowest. For inclination Blueprint had the highest concordance; ExactechGPS had the lowest. Discussion & Conclusion: Despite overall high reliability for measures of glenoid version between 4 frequently utilized shoulder arthroplasty templating softwares, this reliability is significantly affected by glenoid deformity. The programs were overall less reliable when measuring inclination, and a similar trend of decreasing reliability with increasing glenoid deformity emerged that was not statistically significant. Concordance with manual measurement is also variable. Further research is needed to understand how this variability should be accounted for during shoulder arthroplasty preoperative planning. Level of Evidence: Level III; Retrospective Comparative Stud

Interleukin-6 Contributes to Inflammation and Remodeling in a Model of Adenosine Mediated Lung Injury

Chronic lung diseases are the third leading cause of death in the United States due in part to an incomplete understanding of pathways that govern the progressive tissue remodeling that occurs in these disorders. Adenosine is elevated in the lungs of animal models and humans with chronic lung disease where it promotes air-space destruction and fibrosis. Adenosine signaling increases the production of the pro-fibrotic cytokine interleukin-6 (IL-6). Based on these observations, we hypothesized that IL-6 signaling contributes to tissue destruction and remodeling in a model of chronic lung disease where adenosine levels are elevated.We tested this hypothesis by neutralizing or genetically removing IL-6 in adenosine deaminase (ADA)-deficient mice that develop adenosine dependent pulmonary inflammation and remodeling. Results demonstrated that both pharmacologic blockade and genetic removal of IL-6 attenuated pulmonary inflammation, remodeling and fibrosis in this model. The pursuit of mechanisms involved revealed adenosine and IL-6 dependent activation of STAT-3 in airway epithelial cells.These findings demonstrate that adenosine enhances IL-6 signaling pathways to promote aspects of chronic lung disease. This suggests that blocking IL-6 signaling during chronic stages of disease may provide benefit in halting remodeling processes such as fibrosis and air-space destruction

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases