Use of Healthcare Services Two Years before Diagnosis in Danish Sarcoma Patients, 2000-2013

Background. Sarcoma is a rare type of cancer with nonspecific symptoms and uncertain aetiology. Thus, timely diagnosis of sarcomas is a clinical challenge. The aim of this study was to investigate the use of healthcare services 24 months preceding a sarcoma diagnosis compared to a matched cohort. Materials and Methods. The study was a retrospective, population-based, matched cohort registry-study. Patients with sarcoma in Denmark in 2000–2013 were identified in the Danish Sarcoma Registry (n = 2167) and matched 1 : 10 on gender, age, and listed general practice. Using a binomial regression model, incidence rate ratios were calculated for face-to-face contacts in general practice, inpatient and outpatient visits, surgery, paraclinical examinations, and diagnostic imaging. Analyses were stratified for sarcoma subtypes, grade, stage, gender, and presence of comorbidity. Results. The sarcoma patients had significantly increased incidence rate ratios in use of healthcare services compared to the matched cohort a year before their diagnoses. An increase in consultation rates was seen 11 months before diagnosis for inpatient visits, 9 months before diagnosis in general practice and outpatient visits, 8 months before diagnosis for paraclinical examinations, and 4 and 3 months before diagnosis for diagnostic imaging and surgery, respectively. There were no clinical significant differences in length of increased consultation rates between sarcoma type, stage, and grade. Sarcoma patients with comorbidity had persistently higher consultation rates compared to patients without comorbidity. Conclusions. The use of healthcare services among sarcoma patients increased several months before diagnosis in all healthcare sectors. The results reveal a diagnostic time window and a potential to refer, diagnose, and treat sarcoma patients in a timelier manner

Clinical and Histopathological Prognostic Factors in Chondrosarcomas

Purpose. In an attempt to identify clinical and histopathological factors of prognostic importance in chondrosarcomas, 115 cases of malignant and borderline chondromatous tumours were reviewed

A Retrospective Clinicopathological Study of 37 Patients With Chordoma: A Danish National Series

Purpose. There are, in general, few published series on chordoma. It is a rare disease and further data are still needed

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

AbstractOBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model. RESULTS: A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality. CONCLUSION: Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set

Mechanical loading of stem cells for improvement of transplantation outcome in a model of acute myocardial infarction: The role of loading history

Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31+ cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair. © 2012, Mary Ann Liebert, Inc

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

Mechanical loading of stem cells for improvement of transplantation outcome in a model of acute myocardial infarction: the role of loading history

Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5 Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31 + cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair

External validation and adaptation of a dynamic prediction model for patients with high‐grade extremity soft tissue sarcoma

Background and Objectives: A dynamic prediction model for patients with soft tissue sarcoma of the extremities was previously developed to predict updated overall survival probabilities throughout patient follow‐up. This study updates and externally validates the dynamic model. Methods: Data from 3826 patients with high‐grade extremity soft tissue sarcoma, treated surgically with curative intent were used to update the dynamic PERsonalised SARcoma Care (PERSARC) model. Patients were added to the model development cohort and grade was included in the model. External validation was performed with data from 1111 patients treated at a single tertiary center. Results: Calibration plots show good model calibration. Dynamic C‐indices suggest that the model can discriminate between high‐ and low‐risk patients. The dynamic C‐indices at 0, 1, 2, 3, 4, and 5 years after surgery were equal to 0.697, 0.790, 0.822, 0.818, 0.812, and 0.827, respectively. Conclusion: Results from the external validation show that the dynamic PERSARC model is reliable in predicting the probability of surviving an additional 5 years from a specific prediction time point during follow‐up. The model combines patient‐, treatment‐specific and time‐dependent variables such as local recurrence and distant metastasis to provide accurate survival predictions throughout follow‐up and is available through the PERSARC app.Peer reviewe