Mathias Glehr

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients.

Background:Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.Methods:In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS.Results:In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014).Conclusion:In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.

Wikipedia and osteosarcoma: a trustworthy patients' information?

The English version of the online encyclopedia, Wikipedia, has been recently reported to be the prominent source of online health information. However, there is little information concerning the quality of information found in Wikipedia. Therefore, we created a questionnaire asking for scope, completeness, and accuracy of information found on osteosarcoma. Three independent observers tested the English version of Wikipedia, as well as the patient version and the health professional version of the US National Cancer Institute (NCI) website. Answers were verified with authoritative resources and international guidelines. The results of our study demonstrate that the quality of osteosarcoma-related information found in the English Wikipedia is good but inferior to the patient information provided by the NCI. Therefore, non-peer-reviewed commonly used websites offering health information, such as Wikipedia, should include links to more definitive sources, such as those maintained by the NCI and professional international organizations on healthcare treatments. Furthermore, frequent checks should make sure such external links are to the highest quality and to the best-maintained aggregate sites on a given healthcare topic.

Quality of Life After Volar Plate Fixation of Articular Fractures of the Distal Part of the Radius

BACKGROUND Outcome measurement following surgery is increasingly the focus of attention in current health-care debates because of the rising costs of medical care and the large variety of operative options. The purpose of the present study was to correlate quality of life after volar locked plate fixation of unstable intra-articular distal radial fractures with functional and radiographic results as well as with quality-of-life data from population norms. METHODS Fifty-four consecutive patients with intra-articular distal radial fractures and a mean age of sixty-three years were managed with a volar locked plate system. Range of motion, grip strength, and radiographs were assessed at a mean of six years postoperatively. The wrist-scoring systems of Gartland and Werley and Castaing were adopted for the assessment of objective outcomes. The Disabilities of the Arm, Shoulder and Hand and Short Form-36 questionnaires were completed as subjective outcome measures, and the results were compared with United States and Austrian population norms. RESULTS Functional improvement continued for two years postoperatively. At the time of the latest follow-up, >90% of all patients had achieved good or excellent results according to the scoring systems of Gartland and Werley and Castaing. The results of the Short Form-36 questionnaire were similar to the United States and Austrian population norms. The mean Disabilities of the Arm, Shoulder and Hand score was 5 points at two years, and it increased to 13 points at six years. The twenty patients with radiocarpal arthritis had significantly poorer results in the physical component summary measure of the Short Form-36 questionnaire (p = 0.012). CONCLUSIONS The results of the present single-center study show that, following distal radial fracture fixation, wrist arthritis may affect the patients subjective well-being, as documented with the Short Form-36, without influencing the functional outcome. Well-designed longitudinal clinical trials are needed to confirm the findings of the present investigation in terms of quality of life after surgical treatment of intra-articular distal radial fractures.

Epigenetic differences in human cartilage between mild and severe OA

The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome‐wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation‐specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.

Recording of risk-factors and lifestyle counselling in patients at high risk for cardiovascular diseases in European primary care.

Background: Detection and registration of high risk for cardiovascular diseases (CVD) by assessing individual’s absolute cardiovascular risk is recommended in clinical guidelines. Effective interventions to reduce cardiovascular risk are available, but not optimally implemented. The aim of this study was to assess the quality of cardiovascular risk-factor recording and lifestyle counselling in high-risk patients in European primary care and to identify factors related to these clinical processes. Methods: An international cross-sectional observational study was conducted in stratified samples of primary care practices in nine European countries. Patient records were audited, using a structured data-abstraction tool based on internationally developed quality indicators. To identify factors associated with the recording, additional data were collected in a patient survey. Descriptive and multilevel data analyses were conducted. Results: In 268 general practices across Europe, 3723 records of individuals at high risk for cardiovascular diseases were audited. We found important variations in the quality of documentation of risk factors and lifestyle interventions. Recording of risk factors was best for blood pressure (92.5% of audited records, 95% CI 0.89–0.96). Lifestyle advice was recorded best for smoking cessation (65.6%, 95% CI 0.58–0.73) and worst for physical activity (38.8%, 95% CI 0.31–0.47). Of the study population, 50.6% (0.42–0.59) had elevated blood pressure levels, 59.8% (0.51–0.69) had total cholesterol >5 mmol/l, and 30.5% (0.22–0.39) were smokers. Multivariate analyses showed that recording of risk factors and counselling were related to specific patient characteristics more than to country effects. Conclusions: Analysis of different country results can be helpful for developing quality-improvement strategies.

Measurement of the acromiohumeral interval on standardized anteroposterior radiographs: a prospective study of observer variability.

BACKGROUND An acromiohumeral interval narrower than 6 mm has been considered pathologic and strongly indicative for rotator cuff tears by numerous authors. This prospective study assessed interobserver and intraobserver variability in the radiographic measurement of the acromiohumeral interval. MATERIAL AND METHODS Five board-certified orthopedic surgeons independently reviewed 58 blinded, standardized anteroposterior shoulder radiographs. The acromiohumeral interval was measured in millimeters. The 5 investigators classified each image a second time in random order. RESULTS After the same 58 radiographs had been evaluated by the 5 investigators at both examination time points, no significant differences were noted in the interobserver and intraobserver measurements (P < .05). The respective maximum interobserver and intraobserver differences were 4 and 3 mm (range, 0-4 mm). CONCLUSION The assessment of the acromiohumeral interval using standardized anteroposterior radiographs is a reliable and reproducible method of measurement. LEVEL OF EVIDENCE Level 1; Investigating a diagnostic test.

Argyria following the use of silver-coated megaprostheses

The aims of this study were to evaluate the incidence of local argyria in patients with silver-coated megaprostheses and to identify a possible association between argyria and elevated levels of silver both locally and in the blood. Between 2004 and 2011, 32 megaprostheses with silver coatings were implanted in 20 female and 12 male patients following revision arthroplasty for infection or resection of a malignant tumour, and the levels of silver locally in drains and seromas and in the blood were determined. The mean age of the patients was 46 years (10 to 81); one patient died in the immediate post-operative period and was excluded. Seven patients (23%) developed local argyria after a median of 25.7 months (interquartile range 2 to 44.5). Patients with and without local argyria had comparable levels of silver in the blood and aspiration fluids. The length of the implant did not influence the development of local argyria. Patients with clinical evidence of local argyria had no neurological symptoms and no evidence of renal or hepatic failure. Thus, we conclude that the short-term surveillance of blood silver levels in these patients is not required.

Cardiovascular risk management in patients with coronary heart disease in primary care: variation across countries and practices. An observational study based on quality indicators.

BackgroundPrimary care has an important role in cardiovascular risk management (CVRM) and a minimum size of scale of primary care practices may be needed for efficient delivery of CVRM . We examined CVRM in patients with coronary heart disease (CHD) in primary care and explored the impact of practice size.MethodsIn an observational study in 8 countries we sampled CHD patients in primary care practices and collected data from electronic patient records. Practice samples were stratified according to practice size and urbanisation; patients were selected using coded diagnoses when available. CVRM was measured on the basis of internationally validated quality indicators. In the analyses practice size was defined in terms of number of patients registered of visiting the practice. We performed multilevel regression analyses controlling for patient age and sex.ResultsWe included 181 practices (63% of the number targeted). Two countries included a convenience sample of practices. Data from 2960 CHD patients were available. Some countries used methods supplemental to coded diagnoses or other inclusion methods introducing potential inclusion bias. We found substantial variation on all CVRM indicators across practices and countries. We computed aggregated practice scores as percentage of patients with a positive outcome. Rates of risk factor recording varied from 55% for physical activity as the mean practice score across all practices (sd 32%) to 94% (sd 10%) for blood pressure. Rates for reaching treatment targets for systolic blood pressure, diastolic blood pressure and LDL cholesterol were 46% (sd 21%), 86% (sd 12%) and 48% (sd 22%) respectively. Rates for providing recommended cholesterol lowering and antiplatelet drugs were around 80%, and 70% received influenza vaccination. Practice size was not associated to indicator scores with one exception: in Slovenia larger practices performed better. Variation was more related to differences between practices than between countries.ConclusionsCVRM measured by quality indicators showed wide variation within and between countries and possibly leaves room for improvement in all countries involved. Few associations of performance scores with practice size were found.

Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction. The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA. The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties. This study investigated the effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery. RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1β) and then treated with 100 μM resveratrol for 24h. In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array was applied. In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis. In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis. Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary.

No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function

The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow‐up of 33 months (range, 7–59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0–23.0) underwent an instrumented three‐dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow‐up of 33 months.