French translation and validation of the cross-cultural adaptation of the MSTS functional assessment questionnaire completed after tumor surgery.

INTRODUCTION: Malignant tumors of the extremities are uncommon. Their surgical treatment, whether conservative or not, may cause sequelae. Functional assessment of patients is essential for research purposes, but also follow-ups and adaptation of treatments. The Musculoskeletal Tumor Society Rating Scale (MSTS) is a disease-specific functional scoring system often used in English literature. Currently, no studies have been published on a valid French translation of the MSTS, whether for the lower or upper extremities. We, therefore, conducted a prospective study to answer the following questions: (1) Are the proposed adapted French versions of the MSTS valid? (2) Do the psychometric properties of the two versions obtained make their use relevant? MATERIALS AND METHODS: The translation and cross-cultural adaptation were carried out following the recommendations of Beaton and Guillemin to obtain two versions: one for patients who had undergone upper extremity surgery (MSTS-UE) and one for those who had undergone lower extremity surgery (MSTS-LE). A prospective multicenter cohort study was then carried out to analyze the psychometric properties of these two versions. RESULTS: A total of 250 patients from 3 referral centers were enrolled in this study. A confirmatory factor analysis (CFA) demonstrated that the two French versions of the MSTS (MSTS-LE and MSTS-UE) were a good fit with a root mean square error of approximation (RMSEA)<0.08 and a comparative fit index (CFI)>0.90. The psychometric properties of the two versions were validated with internal consistency (Cronbach alpha>0.7), convergent validity of each item with its score (> 0.4), and sufficient criterion validity (Pearson correlation coefficient>0.4). The discriminant validity analysis showed that there was a significant correlation between each version and the performance status (PS) (p<0.05). CONCLUSION: This study produced a French version of the MSTS scoring system and validated the psychometric properties of the two versions obtained (MSTS-UE and MSTS-LE). Therefore, the French MSTS scoring system is a valid measurement that can be used in international studies. LEVEL OF EVIDENCE: I.

Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC.

BACKGROUND: The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. PATIENTS AND METHODS: NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15-30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. RESULTS: Among 3,227 patients aged 15-30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3-83.6) in AYA in RSC and 82.7% (95%CI 79.4-85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively). CONCLUSIONS: This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

Functional and Survival Outcomes of Patients following the Harrington Procedure for Complex Acetabular Metastatic Lesions.

BACKGROUND: The Harrington surgical technique makes it possible to manage complex, extensive bone lesions using pins and cement to consolidate bone for acetabular cup positioning. However, it may be associated with a high reoperation rate, and the functional results of this surgery are not precisely described in the literature. METHODS: In a monocentric retrospective study including all patients operated on using the Harrington procedure associated with THA between 2005 and 2020, we aimed to assess preoperative and postoperative function, reoperation-free survival, and overall survival. RESULTS: Functional improvement was significant for Parker scores (preoperative: 3.6 ± 2.0; 6-month follow-up: 6.6 ± 3.2; 12-month follow-up: 7.6 ± 2.1) and Musculoskeletal Tumor Society (MSTS) scores (preoperative: 31.1 ± 16.2%; 6-month follow-up: 67.7 ± 30.6%; 12-month follow-up: 82.4 ± 24.0%). Of the 21 patients included, the reoperation-free survival rate was 76.1% [CI 95%: 58.1-99.7] at six and twelve months, with the main complications being pin migration (50.0%) and infection (25%). The patient overall survival rate was 76.2% [95% CI: 59.9-96.7] at six months and 61.9% [95% CI: 59.9-96.7] at 12 months. DISCUSSION: These results underlined significant functional improvements following a conventional Harrington procedure, with acceptable reoperation rates.

Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network.

BACKGROUND: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. METHODS: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. RESULTS: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. CONCLUSIONS: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.

Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease.

OBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. METHODS: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N = 85), past smokers (PS) (N = 78) and never smokers (NS) (N = 76). RESULTS: NS had a higher risk profile including hypertension, and CS were younger than PS and NS (-13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861 AU, respectively; p = 0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS + NS) was the strongest predictor of the c-Fos transcript level, (B = 0.042 ± 0.014, p = 0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI). CONCLUSION: Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c-Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease.

Circulating leukocyte telomere length and oxidative stress: a new target for statin therapy.

OBJECTIVES: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation. METHODS AND RESULTS: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without statin therapy. Although patients on statin therapy were older, their mean LTL was longer than patients not under statin therapy (1.29 ± 0.11 vs. 1.25 ± 0.11 T/S ratio, p = 0.008). In contrast, FOS and OGG1 mRNA levels were similar for the 2 groups. LTL decreased with increasing age, FOS, and OGG1 mRNA levels. Statin therapy remained associated with longer LTL, even after adjustment for confounding factors (p = 0.001), and in younger patients (≤ 64 y). Even in groups matched for propensity scores for statin use, LTL was markedly longer in patients under statin therapy. CONCLUSIONS: Our observational study showed that statin therapy was associated with longer LTL. These data bring to light opportunities to identify new targets for early primary preventive treatment strategies. Moreover, our study raised FOS and OGG1 as new relevant biomarkers of LTL.

Serum brain-derived neurotrophic factor and platelet activation evaluated by soluble P-selectin and soluble CD-40-ligand in patients with acute myocardial infarction.

Little is known about the role of neurotrophins (NT) under adult vascular homeostasis in normal and pathological conditions. The NT family, including nerve growth factor and brain-derived neurotrophic factor (BDNF) are expressed in atherosclerotic vessels. Previous studies demonstrated that plasma BDNF levels were increased in the coronary circulation in patients with unstable angina. However, the role of BDNF during the onset and evolution of unstable angina remains to be elucidated. The objective of this study was to evaluate the relationship between BDNF, functional parameters and biological markers associated with inflammatory processes and platelet activation. BDNF serum levels were assessed in patients with acute myocardial infarction (MI) (n = 20) or stable angina pectoris (SAP) (n = 20) who underwent coronary angiography. Serum levels of IL-6, MCP1, sVCAM, soluble CD-40-ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured simultaneously by flux cytometry. Median BDNF levels were higher in the MI than in the SAP group (1730 vs. 877 pg/mL, respectively; P = 0.025). In MI patients, we observed a significant correlation between BDNF and sP-selectin (r = 0.58, P = 0.023), although we found a non-significant trend between BDNF and sCD40L (r = +0.35, P = 0.144). By contrast, no such correlation was observed in SAP patients (r = -0.22, P = 0.425). No difference was observed between the two groups regarding baseline demographics, risk factors, biological data and angiographic findings. The study suggests that BDNF serum levels in MI patients could be related to platelet activation and the inflammatory response. Further studies are needed to investigate the role of NT in the setting of acute MI.