Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

[EN] Despite the complete treatment with surgery, chemotherapy and radiotherapy, patients with glioblastoma have a devasting prognosis. Although the role of extending temozolomide treatment has been explored, the results are inconclusive. Recent evidence suggested that tumor vascularity may be a modulating factor in combination with methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene on the effect of temozolomide-based therapies, opening new possibilities for personalized treatments. Before proposing a prospective interventional clinical study, it is necessary to confirm the beneficial effect of the combined effect of MGMT methylation and moderate tumor vascularity, as well as the lack of benefit of temozolomide in patients with a highly vascular tumor.In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase (MGMT) promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.7) and the new calculated ones (9.1 and 9.8) to analyze the association with survival for different populations according to vascularity and MGMT methylation status. We found that patients included in the moderate-vascular group had longer survival when MGMT is methylated (significant median survival difference of 174 days, p = 0.0129*). However, we did not find significant differences depending on the MGMT methylation status for the high-vascular group (p = 0.9119). In addition, we investigated the combined correlation of MGMT methylation status and rCBV with the prognostic effect of the number of temozolomide cycles, and only significant results were found for the moderate-vascular group. In conclusion, there is a lack of benefit of extending temozolomide treatment for patients with high vascular glioblastomas, even presenting MGMT methylation. Preliminary results suggest that patients with moderate vascularity and methylated MGMT glioblastomas would benefit more from prolonged adjuvant chemotherapy.M.A-T was supported by DPI2016-80054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I+D+i). This work was partially supported by the ALBATROSS project (National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00). This study was partially funded by the Fundacio La Marato TV3 (665/C/2013) (http://www.ccma.cat/tv3/marato/projectes-financats/2012/231/ Accessed on 8th September 2021). (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020-SC1-BHC-2018-2020 (No. 825750) (JMGG). EFG was supported by the European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646 and South-Eastern Norway Regional Health Authority Grant 2021057.Álvarez-Torres, MDM.; Fuster García, E.; Balaña, C.; Puig, J.; Garcia-Gomez, JM. (2021). Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT. Cancers. 13(21):1-14. https://doi.org/10.3390/cancers13215420S114132

Unlocking Bevacizumab's Potential: rCBVmax as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients

[EN] Background: Aberrant vascular architecture and angiogenesis are hallmarks of glioblastoma IDH-wildtype, suggesting that these tumors are suitable for antiangiogenic therapy. Bevacizumab was FDA-approved in 2009 following promising results in two clinical trials. However, its use for recurrent glioblastomas remains a subject of debate, as it does not universally improve patient survival. Purposes: In this study, we aimed to analyze the influence of tumor vascularity on the benefit provided by BVZ and propose preoperative rCBVmax at the high angiogenic tumor habitat as a predictive biomarker to select patients who can benefit the most. Methods: Clinical and MRI data from 106 patients with glioblastoma IDH-wildtype have been analyzed. Thirty-nine of them received BVZ, and the remaining sixty-seven did not receive a second-line treatment. The ONCOhabitats method was used to automatically calculate rCBV. Results: We found a median survival from progression of 305 days longer for patients with moderate vascular tumors who received BVZ than those who did not receive any second-line treatment. This contrasts with patients with high-vascular tumors who only presented a median survival of 173 days longer when receiving BVZ. Furthermore, better responses to BVZ were found for the moderate-vascular group with a higher proportion of patients alive at 6, 12, 18, and 24 months after progression. Conclusions: We propose rCBVmax as a potential biomarker to select patients who can benefit more from BVZ after tumor progression. In addition, we propose a threshold of 7.5 to stratify patients into moderate- and high-vascular groups to select the optimal second-line treatment.M.Á-T was supported by DPI2016-80054-R (Programa Estatal de Promoción del Talento y su Empleabilidad en I + D + i). This work was partially supported by the ALBATROSS project (National Plan for Scientific and Technical Research and Innovation 2017 2020, No. PID2019-104978RB-I00). This study was partially funded by the Fundació La Marató TV3 (665/C/2013). Grant PID2021- 127110OA-I00 (PROGRESS) was funded by MCIN/AEI/10.13039/501100011033 and ERDF, a way of making Europe.Alvarez-Torres, MDM.; Balaña, C.; Fuster García, E.; Puig, J.; Garcia-Gomez, JM. (2024). Unlocking Bevacizumab's Potential: rCBVmax as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients. Cancers. 16(1). https://doi.org/10.3390/cancers1601016116

Ambulatory blood pressure in hypertensive patients with left ventricular hypertrophy: efficacy of first-line combination perindopril/indapamide therapy

Roland Asmar1, Juan Garcia-Puig2, Philippe Gosse3, Yuri A Karpov4, Peter Wilhem De Leeuw5, Dieter Magometschniggs6, Lajos Matos7, Roland Schmieder81Institut Cardiovasculaire, Paris, France; 2Hospital La Paz, Madrid, Spain; 3Hôpital Saint André, Bordeaux, France; 4Russian Academy of Medical Sciences, Moscow, Russia; 5Academisch Ziekenhuis, Maastricht, the Netherlands; 6Institut für Hypertoniker, Vienna, Austria; 7Hungarian Institut of Cardiology, Budapest, Hungary; 8Medizinische FakultÄt, Erlangen GermanyBackground: Ambulatory blood pressure (BP) is more sensitive than office BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH). Methods: In this prospectively designed ancillary study of the PICXEL trial, the effects of first-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52. Results: At study end, both treatments significantly improved ambulatory BP compared with baseline (p ≤ 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) significantly more than enalapril treatment (p < 0.01). No significant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was significantly reduced (−9.1 g/m2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted.Conclusions: First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.Keywords: left ventricular hypertrophy, ambulatory blood pressure monitoring, perindopril, indapamide, enalapri

Production of vegetables and artichokes is associated with lower cardiovascular mortality: An ecological study

Mortality due to cardiovascular disease (CVD), including cerebrovascular disease (CED) and ischaemic heart disease (IHD), was considerably different in eight municipalities of the province of Castellón, Community of Valencia (Spain) during the period of 1991–2011. In addition, these villages showed differences in agricultural practices and production. Since high vegetable consumption has been linked to decreased all-cause, CVD, and CED mortalities, we hypothesized that the diversity in vegetable and artichoke production, used as proxies for their consumption, could be associated with the diversity of mortality rates. In order to test our hypothesis, we estimated the smoothed standardized mortality ratios (SMRs) of CVD, CED, and IHD mortalities and a directed, age-adjusted mortality rate (AMR). We used a multilevel linear regression analysis to account for the ecological nature of our study. After adjustment, the CVD and CED SMRs were inversely associated with vegetable and artichoke production, with a reduction in SMRs for CVD: −0.19 (95% Confidence Interval [CI] −0.31 to −0.07) and −0.42 (95% CI −0.70 to −0.15) per hectare/103 inhabitants, respectively. The SMRs for CED also decreased: −0.68 (95% CI −1.61 to −0.19) and −1.47 (95% CI −2.57 to −0.36) per hectare/103 inhabitants, respectively. The SMRs for IHD were not associated with vegetal and artichoke production. When the directed AMR was used, CED mortality was consistent with the previous results, whereas the CVD mortality association was lost. Our results indicate that vegetable and artichoke production may act as protective factors of CED and CVD mortalities

Felodipine-Metoprolol Combination Tablet: Maintained Health-Related Quality of Life in the Presence of Substantial Blood Pressure Reduction

Background: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). Methods: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. Results: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. Conclusions: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets. Am J Hypertens 2005;18:1313-1319 © 2005 American Journal of Hypertension, Lt

A Systematic Approach For Kinematic Design Of Upper Limb Rehabilitation Exoskeletons

Kinematic structure of an exoskeleton is the most fundamental block of its design and is determinant of many functional capabilities of it. Although numerous upper limb rehabilitation devices have been designed in the recent years, there is not a framework that can systematically guide the kinematic design procedure. Additionally, diversity of currently available devices and the many minute details incorporated to address certain design requirements hinders pinpointing the core kinematics of the available devices to compare them against each other. This makes the review of literature for identifying drawbacks of the state of the art systems a challenging and puzzling task. In fact, lack of a unifying framework makes designing rehabilitation devices an intuitive process and prone to biases from currently available designs. This research work proposes a systematic approach for kinematic design of upper limb rehabilitation exoskeletons based on conceptual design techniques. Having defined a solution neutral problem statement based on the characteristics of an ideal device, the main functionality of the system is divided into smaller functional units via the Functional Decomposition Method. Various directions for concept generation are explored and finally, it has been shown that a vast majority of the current exoskeleton designs fit within the proposed design framework and the defined functionalities

A microservice architecture for real-time IoT data processing: A reusable Web of things approach for smart ports

Major advances in telecommunications and the Internet of Things have given rise to numerous smart city scenarios in which smart services are provided. What was once a dream for the future has now become reality. However, the need to provide these smart services quickly, efficiently, in an interoperable manner and in real time is a cutting-edge technological challenge. Although some software architectures offer solutions in this area, these are often limited in terms of reusability and maintenance by independent modules —involving the need for system downtime when maintaining or evolving, as well as by a lack of standards in terms of the interoperability of their interface. In this paper, we propose a fully reusable microservice architecture, standardized through the use of the Web of things paradigm, and with high efficiency in real-time data processing, supported by complex event processing techniques. To illustrate the proposal, we present a fully reusable implementation of the microservices necessary for the deployment of the architecture in the field of air quality monitoring and alerting in smart ports. The performance evaluation of this architecture shows excellent results

Low-Temperature drying of salted cod (Gadus morhua) assisted by high power ultrasound: Kinetics and physical properties

[EN] Low-temperature convective drying could be considered an affordable alternative to conventional freeze-drying for foodstuffs. The process intensification should be based on non-thermal technologies, such as power ultrasound. Thereby, the aim of this work was to evaluate the air-borne application of power ultrasound on the low-temperature drying of salted cod. For that purpose, drying experiments were carried out at −10, 0, 10 and 20 °C on salted cod slices at 2 m/s with (AIR + US, 20.5 kW/m3) and without ultrasonic application (AIR). In the dried-salted cod, its rehydration capacity was analyzed, as were the microstructural, textural and color changes. At every temperature tested, ultrasound application increased the drying rate; thus, an average increase of 74%was observed in the effective diffusivity. AIR+US dried samples were softer and exhibited a higher rehydration capacity than AIR ones, which was linked to the microstructural changes produced by ultrasound. In addition, color changes were induced by ultrasound application. Industrial relevance: Nowadays, low-temperature convective drying represents a promising alternative for the production of high-quality dried products. However, this technology is mostly limited by the low drying rate, which retards the dehydration process and directly increases the processing costs. Power ultrasound, a nonthermal technology, represents an interesting alternative means of improving low-temperature convective drying due to the fact that acoustic (mechanical)waves may affectwater removal during dryingwith a low heating capacity. Thereby, the ultrasonically enhanced low-temperature convective drying could constitute an affordable alternative to lyophilization (or freeze-drying), which is mainly restricted to high-quality food commodities.The authors acknowledge the financial support both from the Ministerio de Economia y Competitividad (Ref. DPI2012-37466-C03-03) and Carmen Cambra S.L. for their technical support with the selection of the raw material. Cesar Ozuna was the recipient of a fellowship from the Universitat Politecnica de Valencia for his research stay in Aalesund University College.Ozuna López, C.; Cárcel Carrión, JA.; Walde, PM.; García Pérez, JV. (2014). Low-Temperature drying of salted cod (Gadus morhua) assisted by high power ultrasound: Kinetics and physical properties. Innovative Food Science and Emerging Technologies. 23:146-155. https://doi.org/10.1016/j.ifset.2014.03.008S1461552

The therapeutic relationship from the perspective of patients and nurses in the first days of admission: A cross‐sectional study in acute mental health units

The therapeutic relationship (TR) is essential in mental health nursing care and plays a fundamental role in the understanding and treatment of the patient's health status. Despite being a bidirectional construct, limited evidence is available to shed light on this issue in mental health units and even less so in the first days of admission. This study aimed to examine the association and differences between nurses' and patients' perspectives on the establishment of the therapeutic relationship in acute mental health units during the first days of hospitalization. A cross-sectional study was carried out in 12 Spanish mental health units. Data were collected from patients and nurses using the Working Alliance Inventory-Short (WAI-S) questionnaire. A total of 234 cases were analysed, including 234 patients and 58 nurses. The results showed a positive association between nurses' and patients' perspectives on the therapeutic relationship, but also revealed significant differences on each WAI-S dimension. Nurses assigned higher scores compared to patients on the perception of the quality of the therapeutic relationship. The dimensions with the greatest weight from the patients' perspective regarding the quality of the therapeutic relationship were the perception of greater agreement on goals and tasks among nurses. This study demonstrates the importance of establishing shared goals and tasks with nurses from the first days of hospitalization to improve the quality of the therapeutic relationship as perceived by patients. These findings underline the need to consider the different perspectives of both parties to promote a high-quality therapeutic relationship