FLT-PET in previously untreated patients with low-grade glioma can predict their overall survival

BACKGROUND: Low-grade gliomas (LGG) of the brain have an uncertain prognosis, as many of them show continuous growth or upgrade over the course of time. We retrospectively investigated the role of positron emission tomography with 3’-deoxy-3’-[18F]fluorothymidine (FLT-PET) in the prediction of overall survival and event free survival in patients with untreated LGG. No such information is yet available in the literature. MATERIAL AND METHODS: Forty-one patients with previously untreated LGG underwent 55 FLT-PET investigations during their follow-up because of subjective complaints, objective worsening of clinical conditions, equivocal findings or progression on magnetic resonance imaging. The time interval before referral for neurosurgical or radiation treatment was considered to be event free survival, the interval until death as overall survival, respectively. Standardized uptake values (SUV) were measured, and a 3-point scale of subjective assessment was also applied. ROC analysis was used to define cut-off values. The log rank test was used for comparison of Kaplan-Meier survival curves. RESULTS: Eight patients (a total of 9 FLT-PET studies performed) died during follow-up. Progression leading to referral to therapy was recorded in 24 patients (a total of 33 FLT-PET studies). With a cut-off value of SUVmean = 0.236, a median overall survival of 1.007 days was observed in the test positive subgroup while median overall survival for the test negative subgroup was not achieved (p = 0.0002), hazard ratio = 17.6. Subjective assessment resulted in hazard ratio 11.5 (p = 0.0001). Only marginal significance (p=0.0562) was achieved in prediction of event free survival. CONCLUSIONS: Increased FLT uptake in previously untreated patients with LGG is a strong predictor of overall survival. On the other hand, prediction of event free survival was not successful in our cohort, probably because of high prevalence of patients who needed treatment due to symptoms caused by a space-occupying lesion without respect to the proliferative activity of the tumour

A comprehensive thermodynamic study of the U-Am-O ternary system: multiple experimental investigations and Calphad modelling

International audienc

Rating of daytime and nighttime symptoms in RLS: validation of the RLS-6 scale of restless legs syndrome/Willis-Ekbom disease

Background: The International Restless Legs Scale (IRLS) is the most widely used of the scales rating the severity of restless legs syndrome/Willis-Ekbom disease (RLS/WED). It has been well validated and is the primary end point for most of the therapeutic and nontherapeutic studies of RLS/WED. It has excellent psychometric properties, although it does not capture the severity of RLS under a wide variety of circumstances and times of day. Moreover, the IRLS has a large placebo effect. Methods: The Restless Legs Syndrome-6 Scale (RLS-6), however, takes another potentially valuable approach. Six items are rated on a 0-10 scale from no symptoms at 0 to very severe at 10. In addition to questions on satisfaction with sleep and sleepiness, the scale rates the severity of RLS for the past week under four separate circumstances: while falling asleep, during the night, during the day while sitting or lying, and during the day when moving around. The purpose of the current study is to report the validation of the RLS-6 under baseline and therapeutic conditions. Results: The RLS-6 seems to be an acceptable, reliable, precise, valid, and responsive instrument for the assessment of RLS severity in a specific and pragmatic manner. Conclusions: At present, we view the RLS-6 not as a replacement for the IRLS but as a supplement, as each scale provides information not captured by the other.S

Validation of the Kohnen Restless Legs Syndrome-Quality of Life instrument

Background: Due to the symptoms and the sleep disturbances it causes, Restless Legs Syndrome (RLS) has a negative impact on quality of life. Measurement of such impact can be performed by means of questionnaires, such as the Kohnen Restless Legs Syndrome-Quality of Life questionnaire (KRLS-QoL), a specific 12-item instrument that is self-applied by patients. The present study is aimed at performing a first formal validation study of this instrument. Methods: Eight hundred ninety-one patients were included for analysis. RLS severity was assessed by the International Restless Legs Scale (IRLS), Restless Legs Syndrome-6 scales (RLS-6), and Clinical Global Impression of Severity. In addition the Epworth Sleepiness Scale (ESS) was assessed. Acceptability, dimensionality, scaling assumptions, reliability, precision, hypotheses-related validity, and responsiveness were tested. Results: There were missing data in 3.58% patients. Floor and ceiling effects were low for the subscales, global evaluation, and summary index derived from items 1 to 11 after checking that scaling assumptions were met. Exploratory parallel factor analysis showed that the KRLS-QoL may be deemed unidimensional, ie, that all components of the scale are part of one overall general quality of life factor. Indexes of internal consistency (alpha = 0.88), item-total correlation (rS = 0.32-0.71), item homogeneity coefficient (0.41), and scale stability (ICC = 0.73) demonstrated a satisfactory reliability of the KRLS-QoL. Moderate or high correlations were obtained between KRLS-QoL scores and the IRLS, some components of the RLS-6, inter-KRLS-QoL domains, and global evaluations. Known-groups validity for severity levels grouping and responsiveness analysis results were satisfactory, the latter showing higher magnitudes of response for treated than for placebo arms. Conclusions: The KRLS-QoL was proven an acceptable, reliable, valid, and responsive measure to assess the impact of the RLS on quality of life.S

Characterization of Artifact Influence on the Classification of Glucose Time Series Using Sample Entropy Statistics

[EN] This paper analyses the performance of SampEn and one of its derivatives, Fuzzy Entropy (FuzzyEn), in the context of artifacted blood glucose time series classification. This is a difficult and practically unexplored framework, where the availability of more sensitive and reliable measures could be of great clinical impact. Although the advent of new blood glucose monitoring technologies may reduce the incidence of the problems stated above, incorrect device or sensor manipulation, patient adherence, sensor detachment, time constraints, adoption barriers or affordability can still result in relatively short and artifacted records, as the ones analyzed in this paper or in other similar works. This study is aimed at characterizing the changes induced by such artifacts, enabling the arrangement of countermeasures in advance when possible. Despite the presence of these disturbances, results demonstrate that SampEn and FuzzyEn are sufficiently robust to achieve a significant classification performance, using records obtained from patients with duodenal-jejunal exclusion. The classification results, in terms of area under the ROC of up to 0.9, with several tests yielding AUC values also greater than 0.8, and in terms of a leave-one-out average classification accuracy of 80%, confirm the potential of these measures in this context despite the presence of artifacts, with SampEn having slightly better performance than FuzzyEn.The Czech partners were supported by DROIKEM000023001 and RVOVFN64165. No funding was received to support this research work by the Spanish partners.Cuesta Frau, D.; Novák, D.; Burda, V.; Molina Picó, A.; Vargas-Rojo, B.; Mraz, M.; Kavalkova, P.... (2018). Characterization of Artifact Influence on the Classification of Glucose Time Series Using Sample Entropy Statistics. Entropy. 20(11):1-18. https://doi.org/10.3390/e20110871S118201

Influence of Duodenal-Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods

[EN] Diabetes is a disease of great and rising prevalence, with the obesity epidemic being a significant contributing risk factor. Duodenal¿jejunal bypass liner (DJBL) is a reversible implant that mimics the effects of more aggressive surgical procedures, such as gastric bypass, to induce weight loss. We hypothesized that DJBL also influences the glucose dynamics in type II diabetes, based on the induced changes already demonstrated in other physiological characteristics and parameters. In order to assess the validity of this assumption, we conducted a quantitative analysis based on several nonlinear algorithms (Lempel¿Ziv Complexity, Sample Entropy, Permutation Entropy, and modified Permutation Entropy), well suited to the characterization of biomedical time series. We applied them to glucose records drawn from two extreme cases available of DJBL implantation: before and after 10 months. The results confirmed the hypothesis and an accuracy of 86.4% was achieved with modified Permutation Entropy. Other metrics also yielded significant classification accuracy results, all above 70%, provided a suitable parameter configuration was chosen. With the Leave¿One¿Out method, the results were very similar, between 72% and 82% classification accuracy. There was also a decrease in entropy of glycaemia records during the time interval studied. These findings provide a solid foundation to assess how glucose metabolism may be influenced by DJBL implantation and opens a new line of research in this field.The Czech clinical partners were supported by DRO IKEM 000023001 and RVO VFN 64165. The Czech technical partners were supported by Research Centre for Informatics grant numbers CZ.02.1.01/0.0/16 - 019/0000765 and SGS16/231/OHK3/3T/13-Support of interactive approaches to biomedical data acquisition and processing. No funding was received to support this research work by the Spanish and British partnersCuesta Frau, D.; Novák, D.; Burda, V.; Abasolo, D.; Adjei, T.; Varela, M.; Vargas, B.... (2019). Influence of Duodenal-Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods. Complexity. 2019. https://doi.org/10.1155/2019/6070518S2019Kassirer, J. P., & Angell, M. (1998). Losing Weight — An Ill-Fated New Year’s Resolution. New England Journal of Medicine, 338(1), 52-54. doi:10.1056/nejm199801013380109Van Gaal, L., & Dirinck, E. (2016). Pharmacological Approaches in the Treatment and Maintenance of Weight Loss. Diabetes Care, 39(Supplement 2), S260-S267. doi:10.2337/dcs15-3016De Jonge, C., Rensen, S. S., Verdam, F. J., Vincent, R. P., Bloom, S. R., Buurman, W. A., … Greve, J. W. M. (2015). Impact of Duodenal-Jejunal Exclusion on Satiety Hormones. Obesity Surgery, 26(3), 672-678. doi:10.1007/s11695-015-1889-yMuñoz, R., Dominguez, A., Muñoz, F., Muñoz, C., Slako, M., Turiel, D., … Escalona, A. (2013). Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients. Surgical Endoscopy, 28(4), 1056-1062. doi:10.1007/s00464-013-3283-yOgata, H., Tokuyama, K., Nagasaka, S., Ando, A., Kusaka, I., Sato, N., … Yamamoto, Y. (2007). Long-range Correlated Glucose Fluctuations in Diabetes. Methods of Information in Medicine, 46(02), 222-226. doi:10.1055/s-0038-1625411Rodríguez de Castro, C., Vigil, L., Vargas, B., García Delgado, E., García Carretero, R., Ruiz-Galiana, J., & Varela, M. (2016). Glucose time series complexity as a predictor of type 2 diabetes. Diabetes/Metabolism Research and Reviews, 33(2), e2831. doi:10.1002/dmrr.2831DeFronzo, R. A. (2004). Pathogenesis of type 2 diabetes mellitus. Medical Clinics of North America, 88(4), 787-835. doi:10.1016/j.mcna.2004.04.013Zhang, X.-S., Roy, R. J., & Jensen, E. W. (2001). EEG complexity as a measure of depth of anesthesia for patients. IEEE Transactions on Biomedical Engineering, 48(12), 1424-1433. doi:10.1109/10.966601Bandt, C., & Pompe, B. (2002). Permutation Entropy: A Natural Complexity Measure for Time Series. Physical Review Letters, 88(17). doi:10.1103/physrevlett.88.174102Bian, C., Qin, C., Ma, Q. D. Y., & Shen, Q. (2012). Modified permutation-entropy analysis of heartbeat dynamics. Physical Review E, 85(2). doi:10.1103/physreve.85.021906Zhao, L., Wei, S., Zhang, C., Zhang, Y., Jiang, X., Liu, F., & Liu, C. (2015). Determination of Sample Entropy and Fuzzy Measure Entropy Parameters for Distinguishing Congestive Heart Failure from Normal Sinus Rhythm Subjects. Entropy, 17(12), 6270-6288. doi:10.3390/e17096270Weinstein, R. L., Schwartz, S. L., Brazg, R. L., Bugler, J. R., Peyser, T. A., & McGarraugh, G. V. (2007). Accuracy of the 5-Day FreeStyle Navigator Continuous Glucose Monitoring System: Comparison with frequent laboratory reference measurements. Diabetes Care, 30(5), 1125-1130. doi:10.2337/dc06-1602Weber, C., & Schnell, O. (2009). The Assessment of Glycemic Variability and Its Impact on Diabetes-Related Complications: An Overview. Diabetes Technology & Therapeutics, 11(10), 623-633. doi:10.1089/dia.2009.0043Cuesta-Frau, D., Miró-Martínez, P., Oltra-Crespo, S., Jordán-Núñez, J., Vargas, B., González, P., & Varela-Entrecanales, M. (2018). Model Selection for Body Temperature Signal Classification Using Both Amplitude and Ordinality-Based Entropy Measures. Entropy, 20(11), 853. doi:10.3390/e20110853Cuesta–Frau, D., Miró–Martínez, P., Oltra–Crespo, S., Jordán–Núñez, J., Vargas, B., & Vigil, L. (2018). Classification of glucose records from patients at diabetes risk using a combined permutation entropy algorithm. Computer Methods and Programs in Biomedicine, 165, 197-204. doi:10.1016/j.cmpb.2018.08.018Cuesta–Frau, D., Varela–Entrecanales, M., Molina–Picó, A., & Vargas, B. (2018). Patterns with Equal Values in Permutation Entropy: Do They Really Matter for Biosignal Classification? Complexity, 2018, 1-15. doi:10.1155/2018/1324696Mayer, C. C., Bachler, M., Hörtenhuber, M., Stocker, C., Holzinger, A., & Wassertheurer, S. (2014). Selection of entropy-measure parameters for knowledge discovery in heart rate variability data. BMC Bioinformatics, 15(S6). doi:10.1186/1471-2105-15-s6-s2Sheng Lu, Xinnian Chen, Kanters, J. K., Solomon, I. C., & Chon, K. H. (2008). Automatic Selection of the Threshold Value $r$ for Approximate Entropy. IEEE Transactions on Biomedical Engineering, 55(8), 1966-1972. doi:10.1109/tbme.2008.919870Crenier, L., Lytrivi, M., Van Dalem, A., Keymeulen, B., & Corvilain, B. (2016). 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Comparison of Inflammatory Response to Transgastric and Transcolonic NOTES

Aims. The aim of our study was to determine the physiologic impact of NOTES and to compare the transgastric and transcolonic approaches. Methods. Thirty pigs were randomized to transgastric, transcolonic, or laparoscopic peritoneoscopy. Blood was drawn and analyzed for C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1β, IL-6, WBCs, and platelets. Results. Endoscopic closure with an OTSC was successful in all 20 animals. The postoperative course was uneventful in all animals. CRP values rose on day 1 in all animals and slowly declined to baseline levels on day 14 with no differences between the groups (P>0.05, NS). The levels of TNF-α were significantly increased in the transcolonic group (P<0.01); however this difference was already present prior to the procedure and remained unchanged. No differences were observed in IL1-β and IL-6 values. There was a temporary rise of WBC on day 1 and of platelets on day 7 in all groups (P>0.05, NS). Conclusions. Transgastric, transcolonic, and laparoscopic peritoneoscopy resulted in similar changes in systemic inflammatory markers. Our findings do not support the assumption that NOTES is less invasive than laparoscopy

Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing

Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas. FDC secreted protein (FDCSP) and Serglycin (SRGN) proved to be specific markers of FDC and related tumor. They showed better specificity and sensitivity values than some well known markers used in FDC sarcoma diagnosis (specificity: 98.6%, and 100%, respectively; sensitivity: 72.73% and 68.18%, respectively). In our cohorts CXCL13, CD21, CD35, FDCSP and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis. In summary, by WTS we identified two novel FDC markers and by the analysis of a wide cohort of cases and controls we propose an efficient marker panel for the diagnosis of this rare and enigmatic tumor