Multilingual RECIST classification of radiology reports using supervised learning.

Objectives: The objective of this study is the exploration of Artificial Intelligence and Natural Language Processing techniques to support the automatic assignment of the four Response Evaluation Criteria in Solid Tumors (RECIST) scales based on radiology reports. We also aim at evaluating how languages and institutional specificities of Swiss teaching hospitals are likely to affect the quality of the classification in French and German languages. Methods: In our approach, 7 machine learning methods were evaluated to establish a strong baseline. Then, robust models were built, fine-tuned according to the language (French and German), and compared with the expert annotation. Results: The best strategies yield average F1-scores of 90% and 86% respectively for the 2-classes (Progressive/Non-progressive) and the 4-classes (Progressive Disease, Stable Disease, Partial Response, Complete Response) RECIST classification tasks. Conclusions: These results are competitive with the manual labeling as measured by Matthew's correlation coefficient and Cohen's Kappa (79% and 76%). On this basis, we confirm the capacity of specific models to generalize on new unseen data and we assess the impact of using Pre-trained Language Models (PLMs) on the accuracy of the classifiers.

Endocrinological and inflammatory markers in individuals with spinal cord injury: A systematic review and meta-analysis.

Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker changes in this elevated risk group. We focused specifically on the endocrine and inflammation profile differences between SCI and able-bodied individuals (ABI). Our aim was to determine the differences in inflammatory markers and endocrine profiles between SCI and ABI. We systematically searched 4 electronic databases for relevant studies. Human observational (cross-sectional, cohort, case-control) studies that compared biomarkers of interest between SCI and ABI population were included. Weighted mean difference between SCI and ABI was calculated using random-effects models. Heterogeneity was computed using I2 statistic and chi-squared test. Study quality was evaluated through the Newcastle-Ottawa Scale. The search strategy yielded a total of 2,603 studies from which 256 articles were selected for full-text assessment. Sixty-two studies were included in the meta-analysis. SCI individuals had higher levels of pro-inflammatory C-reactive protein and IL-6 than ABI. Creatinine and 25-hydroxyvitamin D3 levels were lower in SCI than ABI. Total testosterone levels and IGF-1 were also found to be lower, while cortisol and leptin levels were higher in SCI when compared to ABI. Accordingly, meta-regression, subgroup analysis, and leave-one-out analysis were performed, however, they were only able to partially explain the high levels of heterogeneity. Individuals with SCI show higher levels of inflammatory markers and present significant endocrinological changes when compared to ABI. Moreover, higher incidence of obesity, diabetes, osteoporosis, and hypogonadism in SCI individuals, together with decreased creatinine levels reflect some of the readily measurable aspects of the phenotype changes in the SCI group. These findings need to be considered in anticipating medically related complications and personalizing SCI medical care.

Cohort profile: The Swiss Transplant Cohort Study (STCS): A nationwide longitudinal cohort study of all solid organ recipients in Switzerland.

PURPOSE: The Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine. PARTICIPANTS: Over 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients. FINDINGS TO DATE: Detailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the last decade. Interdisciplinary contributions in diverse fields of transplantation medicine such as infectious diseases, genomics, oncology, immunology and psychosocial science have resulted in approximately 70 scientific papers getting published in peer-review journals so far. FUTURE PLANS: The STCS will deepen its efforts in personalised medicine and digital epidemiology, and will also focus on allocation research and the use of causal inference methods to make complex matters in transplant medicine more understandable and transparent.

Time Requirement and Feasibility of a Systematic Quality Peer Review of Reporting in Radiology.

OBJECTIVE: To estimate the human resources required for a retrospective quality review of different percentages of all routine diagnostic procedures in the Department of Radiology at Bern University Hospital, Switzerland. MATERIALS AND METHODS: Three board-certified radiologists retrospectively evaluated the quality of the radiological reports of a total of 150 examinations (5 different examination types: abdominal CT, chest CT, mammography, conventional X-ray images and abdominal MRI). Each report was assigned a RADPEER score of 1 to 3 (score 1: concur with previous interpretation; score 2: discrepancy in interpretation/not ordinarily expected to be made; score 3: discrepancy in interpretation/should be made most of the time). The time (in seconds, s) required for each review was documented and compared. A sensitivity analysis was conducted to calculate the total workload for reviewing different percentages of the total annual reporting volume of the clinic. RESULTS: Among the total of 450 reviews analyzed, 91.1 % (410/450) were assigned a score of 1 and 8.9 % (40/450) were assigned scores of 2 or 3. The average time (in seconds) required for a peer review was 60.4 s (min. 5 s, max. 245 s). The reviewer with the greatest clinical experience needed significantly less time for reviewing the reports than the two reviewers with less clinical expertise (p < 0.05). Average review times were longer for discrepant ratings with a score of 2 or 3 (p < 0.05). The total time requirement calculated for reviewing all 5 types of examination for one year would be more than 1200 working hours. CONCLUSION: A retrospective peer review of reports of radiological examinations using the RADPEER system requires considerable human resources. However, to improve quality, it seems feasible to peer review at least a portion of the total yearly reporting volume. KEY POINTS: · A systematic retrospective assessment of the content of radiological reports using the RADPEER system involves high personnel costs.. · The retrospective assessment of all reports of a clinic or practice seems unrealistic due to the lack of highly specialized personnel.. · At least part of all reports should be reviewed with the aim of improving the quality of reports.. CITATION FORMAT: · Maurer MH, Brönnimann M, Schroeder C et al. Time Requirement and Feasibility of a Systematic Quality Peer Review of Reporting in Radiology. Fortschr Röntgenstr 2021; 193: 160 - 167.

SPHN/PHRT - MedCo in Action: Empowering the Swiss Molecular Tumor Board with Privacy-Preserving and Real-Time Patient Discovery.

MedCo is the first operational system that makes sensitive medical-data available for research in a simple, privacy-conscious and secure way. It enables a consortium of clinical sites to collectively protect their data and to securely share them with investigators, without single points of failure. In this short paper, we report on our ongoing effort for the operational deployment of MedCo within the context of the Swiss Personalized Health Network (SPHN) for the Swiss Molecular Tumor Board.

Renal Function-Adjusted D-Dimer Levels in Critically Ill Patients With Suspected Thromboembolism.

OBJECTIVES: Diagnosing thromboembolic disease typically includes D-dimer testing and use of clinical scores in patients with low to intermediate pretest probability. However, renal dysfunction is often observed in patients with thromboembolic disease and was previously shown to be associated with increased D-dimer levels. We seek to validate previously suggested estimated glomerular filtration rate-adjusted D-dimer cutoff levels. Furthermore, we strive to explore whether the type of renal dysfunction affects estimated glomerular filtration rate-adjusted D-dimer test characteristics. DESIGN: Single-center retrospective data analysis from electronic healthcare records of all emergency department patients admitted for suspected thromboembolic disease. SETTING: Tertiary care academic hospital. SUBJECTS: Exclusion criteria were as follows: age less than 16 years old, patients with active bleeding, and/or incomplete records. INTERVENTIONS: Test characteristics of previously suggested that estimated glomerular filtration rate-adjusted D-dimer cutoff levels (> 333 µg/L [estimated glomerular filtration rate, > 60 mL/min/1.73 m], > 1,306 µg/L [30-60 mL/min/1.73 m], and > 1,663 µg/L [< 30 mL/min/1.73 m]) were validated and compared with the conventional D-dimer cutoff level of 500 µg/L. MAIN RESULTS: A total of 14,477 patients were included in the final analysis, with 467 patients (3.5%) diagnosed with thromboembolic disease. Renal dysfunction was observed in 1,364 (9.4%) of the total population. When adjusted D-dimer levels were applied, test characteristics remained stable: negative predictive value (> 99%), sensitivity (91.2% vs 93.4%), and specificity (42.7% vs 50.7%) when compared with the conventional D-dimer cutoff level to rule out thromboembolic disease (< 500 µg/L). Comparable characteristics were also observed when adjusted D-dimer cutoff levels were applied in patients with acute kidney injury (negative predictive value, 98.8%; sensitivity, 95.8%; specificity, 39.2%) and/or "acute on chronic" renal dysfunction (negative predictive value, 98.0%; sensitivity, 92.9%; specificity, 48.5%). CONCLUSIONS: D-Dimer cutoff levels adjusted for renal dysfunction appear feasible and safe assessing thromboembolic disease in critically ill patients. Furthermore, adjusted D-dimer cutoff levels seem reliable in patients with acute kidney injury and "acute on chronic" renal dysfunction. In patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m, the false-positive rate can be reduced when estimated glomerular filtration rate-adjusted D-dimer cutoff levels are applied.

Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation.

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease is independently associated with all-cause mortality. Since inflammation is characteristic of chronic kidney disease and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of chronic kidney disease showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of chronic kidney disease.

The links of hepcidin and erythropoietin in the interplay of inflammation and iron deficiency in a large observational study of rheumatoid arthritis.

Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross-sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti-cytokine-specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti-tumour necrosis factor-alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.

Bootstrap-based testing approaches for the assessment of the diagnostic accuracy of biomarkers subject to a limit of detection.

Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic curve analysis frequently involves a limit of detection imposed by the laboratory analytical system precision. As a consequence, measurements below a certain level are undetectable and ignoring these is known to lead to negatively biased estimates of the area under the receiver operating characteristic curve. In this article, we introduce two receiver operating characteristic curve-based parametric approaches that tackle the issue of correct assessment of diagnostic markers in the presence of a limit of detection. Proposed approaches are simulation-based utilising bootstrap methodology. Non-parametric alternatives that are naively used in the literature do not solve the inherent problem of limit of detection values which are treated as censored observations. However, the latter seems to perform adequately well in our simulation study. Nonparametric bootstrap was consistently used throughout, while other bootstrap alternatives performed similarly in our pilot simulation study. The simulation study involves the comparison of parametric and non-parametric options described here versus alternative strategies that are routinely used in the literature. We apply all methods to a study-setting resembling a chemical quasi-standard situation, where compound tumour biomarkers were searched within a multi-variable set of measurements to discriminate between two groups, namely colorectal cancer and controls. We focus in the assessment of glutamine and methionine.

PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn's disease.

BACKGROUND: Accurate classification of patients with inflammatory bowel disease into the subtypes ulcerative colitis (UC) and Crohn's disease (CD) is still a challenge, but important for therapy and prognosis. OBJECTIVES: To evaluate the diagnostic utility of anti-neutrophil cytoplasmic antibodies specific for proteinase-3 (PR3-ANCA) for ulcerative colitis (UC) and the value of an antibody panel incorporating PR3-ANCA to differentiate between Crohn's disease (CD) and UC. STUDY DESIGN: In this cohort study, 122 pediatric and adolescent individuals were retrospectively included (61 IBD patients of two clinical centers, 61 non-IBD controls). All subjects had a comprehensive antibody profile done from stored sera taken close to time of diagnosis. By employing quasi-exhaustive logistic regression the best discriminative model for UC and CD,subjects was determined in a training cohort and confirmed in a validation cohort. RESULTS: PR3-ANCA was specifically associated with UC (odds ratio (OR), 17.6; 95% confidence interval (CI); 3.6, 87); P < .001). A four antibody-panel including PR3-ANCA had an AUC of 90.81% (95%CI; 81.93, 99.69) to distinguish between UC and CD in the training cohort. In a smaller external validation cohort, the AUC was 84.13% (95%CI; 64.21, 100) for accurate diagnosis of CD and UC. CONCLUSION: PR3-ANCA is highly specific for UC. The differentiating capability of a panel, which contains PR3-ANCA and weighs broadly available antibodies, is superior and utilization of the panel can support accurate classification in the work-up of pediatric and adolescent patients with IBD patients.

Exhaled breath condensate as a potential biomarker tool for idiopathic pulmonary fibrosis-a pilot study.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. There is an urgent need to better diagnose and monitor IPF patients as new treatments which slow down disease progression are now available. Exhaled breath condensate (EBC) is easily and non-invasively collected, but analysis of potential biomarkers is difficult due to low concentrations and methodological limitations. We used a non-targeted metabolomics approach to identify discriminatory metabolic profiles that distinguish IPF patients from healthy controls. For the pilot study set, we collected EBC from 10 stable IPF patients and 10 lung healthy controls. Samples were analyzed by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry in positive and negative ion mode. After data processing and statistical analysis, 58 metabolites were found to be discriminative between IPF patients and controls in the positive ion mode. One metabolite candidate m/z = 341.3514 at a retention time of 9.94 min was 2.5-fold up-regulated in IPF patients compared to healthy controls and validated in a second set of eight IPF patients and healthy controls. The identity of this metabolic feature still remains elusive. Our preliminary results identified a distinguished EBC profile of IPF patients compared to controls. Although these results need to be confirmed in additional individuals, EBC sampling for diagnosis and/or monitoring of IPF patients is a promising new method, which should be further explored. The EBC samples have been obtained within the clinical trial NCT02173145 at baseline.

Sparse Proteomics Analysis - a compressed sensing-based approach for feature selection and classification of high-dimensional proteomics mass spectrometry data.

BACKGROUND: High-throughput proteomics techniques, such as mass spectrometry (MS)-based approaches, produce very high-dimensional data-sets. In a clinical setting one is often interested in how mass spectra differ between patients of different classes, for example spectra from healthy patients vs. spectra from patients having a particular disease. Machine learning algorithms are needed to (a) identify these discriminating features and (b) classify unknown spectra based on this feature set. Since the acquired data is usually noisy, the algorithms should be robust against noise and outliers, while the identified feature set should be as small as possible. RESULTS: We present a new algorithm, Sparse Proteomics Analysis (SPA), based on the theory of compressed sensing that allows us to identify a minimal discriminating set of features from mass spectrometry data-sets. We show (1) how our method performs on artificial and real-world data-sets, (2) that its performance is competitive with standard (and widely used) algorithms for analyzing proteomics data, and (3) that it is robust against random and systematic noise. We further demonstrate the applicability of our algorithm to two previously published clinical data-sets.

Increased endothelial microparticles and oxidative stress at extreme altitude.

PURPOSE: Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. METHODS: 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. RESULTS: 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. CONCLUSION: Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency.

In the present study, we wanted to (1) evaluate whether high-sensitive troponin T levels correlate with the grade of renal insufficiency and (2) test the accuracy of high-sensitive troponin T determination in patients with renal insufficiency for diagnosis of acute myocardial infarction (AMI). In this cross-sectional analysis, all patients who received serial measurements of high-sensitive troponin T from August 1, 2010, to October 31, 2012, at the Department of Emergency Medicine were included. We analyzed data on baseline characteristics, reason for referral, medication, cardiovascular risk factors, and outcome in terms of presence of AMI along with laboratory data (high-sensitive troponin T, creatinine). A total of 1,514 patients (67% male, aged 65 ± 16 years) were included, of which 382 patients (25%) had moderate to severe renal insufficiency and significantly higher levels of high-sensitive troponin T on admission (0.028 vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T correlated inversely with the estimated glomerular filtration rate (R = -0.12, p <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to 0.51). The area under the curve of the receiver operating characteristic for all patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029) for patients with a Modification of Diet in Renal Disease estimated glomerular filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535 (SE 0.056) for patients with moderate to severe renal insufficiency presenting with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for presence of AMI of a baseline measurement of high-sensitive troponin in patients with renal insufficiency was poor and resembles tossing a coin.

Potentials and pitfalls of clinical peptidomics and metabolomics.

Clinical peptidomics and metabolomics are two emerging "-omics" technologies with the potential not only to detect disease-specific markers, but also to give insight into the disease dependency of degradation processes and metabolic pathway alterations. However, despite their rapid evolution and major investments, a clinical breakthrough, such as the approval of a major cancer biomarker, is still out of sight. What are the reasons for this failure? In this review we focus on three important factors: sensitivity, specificity and the avoidance of bias. The way to clinical implementation of peptidomics and metabolomics is still hampered by many of the problems that had to be solved for genomics and proteomics in the past, as well as new ones that require the creation of new analytic, computational and interpretative techniques. The greatest challenge, however, will be the integration of information from different "-omics" subdisciplines into straightforward answers to clinical questions, for example, in the form of new, superior "meta-markers".

Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma.

Metabolomics as one of the most rapidly growing technologies in the "-omics" field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Formula: see text] We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and-despite all its current limitations-can deliver marker panels with high selectivity even in multi-class settings.

Hypercalcemia in the ED: prevalence, etiology, and outcome.

PURPOSES: The aim of the study was to describe the prevalence, demographic, and clinical characteristics and etiologies of hypercalcemia in emergency department patients. BASIC PROCEDURES: In this retrospective cross-sectional descriptive study, all patients admitted between April 1, 2008, and March 31, 2011, to the emergency department of Inselspital, University Hospital Bern, were screened for the presence of hypercalcemia, defined as a serum calcium exceeding 2.55 mmol/L after correction for serum albumin. Demographic, laboratory, and outcome data were gathered. A detailed medical record review was performed to identify causes of hypercalcemia. MAIN FINDINGS: During the study period, 14 984 patients (19% of all admitted patients) received a measurement of serum calcium. Of these, 116 patients (0.7%) presented with hypercalcemia. Median serum calcium was 2.72 mmol/L (first quartile, 2.64; third quartile, 2.88), with 4.3 mmol/L being the maximum serum calcium value observed. Underlying malignancy in 44% of patients and hyperparathyroidism in 20% (12% secondary and 8% primary) were the leading causes of hypercalcemia. Twenty-six percent of patients presented with symptomatic hypercalcemia. Weakness was the most common symptom of hypercalcemia, followed by nausea and disorientation. PRINCIPAL CONCLUSIONS: Hypercalcemia is a rare but harmful electrolyte disorder in emergency department patients. Unspecific symptoms such as a change in mental state, weakness, or gastrointestinal symptoms should prompt physicians to order serum calcium measurements, at least in patients with known malignancy or renal insufficiency.

Serum amino acid profiles and their alterations in colorectal cancer.

Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

Fatty acid and peptide profiles in plasma membrane and membrane rafts of PUFA supplemented RAW264.7 macrophages.

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers.

Effect of increased exercise in school children on physical fitness and endothelial progenitor cells: a prospective randomized trial.

BACKGROUND: The aim of this prospective, randomized study was to examine whether additional school exercise lessons would result in improved peak oxygen uptake (primary end point) and body mass index-standard deviation score, motor and coordinative abilities, circulating progenitor cells, and high-density lipoprotein cholesterol (major secondary end points). METHODS AND RESULTS: Seven sixth-grade classes (182 children, aged 11.1+/-0.7 years) were randomized to an intervention group (4 classes with 109 students) with daily school exercise lessons for 1 year and a control group (3 classes with 73 students) with regular school sports twice weekly. The significant effects of intervention estimated from ANCOVA adjusted for intraclass correlation were the following: increase of peak o(2) (3.7 mL/kg per minute; 95% confidence interval, 0.3 to 7.2) and increase of circulating progenitor cells evaluated by flow cytometry (97 cells per 1 x 10(6) leukocytes; 95% confidence interval, 13 to 181). No significant difference was seen for body mass index-standard deviation score (-0.08; 95% confidence interval, -0.28 to 0.13); however, there was a trend to reduction of the prevalence of overweight and obese children in the intervention group (from 12.8% to 7.3%). No treatment effect was seen for motor and coordinative abilities (4; 95% confidence interval, -1 to 8) and high-density lipoprotein cholesterol (0.03 mmol/L; 95% confidence interval, -0.08 to 0.14). CONCLUSIONS: Regular physical activity by means of daily school exercise lessons has a significant positive effect on physical fitness (o(2)max). Furthermore, the number of circulating progenitor cells can be increased, and there is a positive trend in body mass index-standard deviation score reduction and motor ability improvement. Therefore, we conclude that primary prevention by means of increasing physical activity should start in childhood. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Identifier: NCT00176371.