Citations

Abstract Introduction The semantic interoperability of electronic healthcare records (EHRs) systems is a major challenge in the medical informatics area. International initiatives pursue the use of semantically interoperable clinical models, and ontologies have frequently been used in semantic interoperability efforts. The objective of this paper is to propose a generic, ontology-based, flexible approach for supporting the automatic transformation of clinical models, which is illustrated for the transformation of Clinical Element Models (CEMs) into openEHR archetypes. Methods Our transformation method exploits the fact that the information models of the most relevant EHR specifications are available in the Web Ontology Language (OWL). The transformation approach is based on defining mappings between those ontological structures. We propose a way in which CEM entities can be transformed into openEHR by using transformation templates and OWL as common representation formalism. The transformation architecture exploits the reasoning and inferencing capabilities of OWL technologies. Results We have devised a generic, flexible approach for the transformation of clinical models, implemented for the unidirectional transformation from CEM to openEHR, a series of reusable transformation templates, a proof-of-concept implementation, and a set of openEHR archetypes that validate the methodological approach. Conclusions We have been able to transform CEM into archetypes in an automatic, flexible, reusable transformation approach that could be extended to other clinical model specifications. We exploit the potential of OWL technologies for supporting the transformation process. We believe that our approach could be useful for international efforts in the area of semantic interoperability of EHR systems.

While elective total hip arthroplasty (THA) for end-stage osteoarthritis (OA) improves pain, mobility function, and quality of life in most cases, a large proportion of patients suffer persistent muscle atrophy, pain, and mobility impairment. Extensive skeletal muscle damage is unavoidable in these surgical procedures, and it stands to reason that poor recovery and long-term mobility impairment among some individuals after THA is linked to failed muscle regeneration and regrowth following surgery and that local muscle inflammation susceptibility (MuIS) is a major contributing factor. Here we present results of two integrated studies. In study 1, we compared muscle inflammation and protein metabolism signaling in elective THA ( n = 15) vs. hip fracture/trauma (HFX; n = 11) vs. nonsurgical controls (CON; n = 19). In study 2, we compared two subgroups of THA patients dichotomized into MuIS (+) ( n = 7) or MuIS (−) ( n = 7) based on muscle expression of TNF-like weak inducer of apoptosis (TWEAK) receptor (Fn14). As expected, HFX demonstrated overt systemic and local muscle inflammation and hypermetabolism. By contrast, no systemic inflammation was detected in elective THA patients; however, local muscle inflammation in the perioperative limb was profound in MuIS (+) and was accompanied by suppressed muscle protein synthesis compared with MuIS (−) . Muscle from the contralateral limb of MuIS (+) was unaffected, providing evidence of a true inflammation susceptibility localized to the muscle surrounding the hip with end-stage OA. We suggest MuIS status assessed at the time of surgery may be a useful prognostic index for muscle recovery potential and could therefore provide the basis for a personalized approach to postsurgery rehabilitation.

Abstract The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8+ T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

Purpose The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making. Patients and Methods GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis. Results The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01). Conclusion In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

Purpose We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients and Methods Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. Results In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). Conclusion The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.

Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development.

ABSTRACTThe purpose of this study was to investigate the biomechanical properties of modified repair techniques for flexor tendon reconstruction and the effects of surface modification using carbodiimide‐derivatized synovial fluid plus gelatin (cd‐SF‐G), compared to the traditional repair techniques. The second and fifth digits from 16 canine forepaws were randomly divided into 4 groups: (1) traditional graft repairs (TGR group) including distal Bunnell repair and proximal Pulvertaft weave repair; (2) modified graft repairs (MGR group) including distal graft bony attachment repair and proximal step‐cut repair; (3) group TGR coated with cd‐SF‐G (TGR‐C group); and (4) group MGR coated with cd‐SF‐G (MGR‐C group). Digit normalized work of flexion (nWOF), ultimate failure strength, and stiffness were measured. The nWOF in MGR group was significantly less than TGR group (p < 0.05). The nWOF in groups treated with cd‐SF‐G was significantly less than their untreated counterparts (p < 0.05). Ultimate load to failure of the MGR‐C group was significantly greater than the TGR‐C group (p < 0.05), but no significant difference in stiffness was found between these two groups. The modified techniques cannot only improve tendon gliding abilities but can also improve breaking strength. Additionally, surface modification with cd‐SF‐G significantly decreased the work of flexion. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:731–737, 2015.