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Krzysztof Sztandera,1 Michał Gorzkiewicz,1,2 Mateusz Bątal,1 Valeria Arkhipova,3,4 Nadezhda Knauer,3,5,6 Javier Sánchez-Nieves,7,8 Fco Javier de la Mata,7– 9 Rafael Gómez,7– 9 Evgeny Apartsin,3,4,10 Barbara Klajnert-Maculewicz1 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, 90-236, Poland; 2Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 3Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; 4Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russia; 5Research Institute of Fundamental and Clinical Immunology, Novosibirsk, 630099, Russia; 6Clinic for Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, 40225, Germany; 7Departamento de Química Orgánica y Química Inorgánica, UAH-IQAR, Alcalá de Henares, 28805, Spain; 8Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, 28034, Spain; 10Laboratoire de Chimie de Coordination CNRS, Toulouse, 31077, FranceCorrespondence: Barbara Klajnert-Maculewicz, Department of General Biophysics, Pomorska 141/143, Łódź, 90-236, Poland, Tel +48 42 635 44 29, Fax +48 42 635 4474, Email barbara.klajnert@biol.uni.lodz.plBackground: The search for new formulations for photodynamic therapy is intended to improve the outcome of skin cancer treatment using significantly reduced doses of photosensitizer, thereby avoiding side effects. The incorporation of photosensitizers into nanoassemblies is a versatile way to increase the efficiency and specificity of drug delivery into target cells. Herein, we report the loading of rose bengal into vesicle-like constructs of amphiphilic triazine-carbosilane dendrons (dendrimersomes) as well as biophysical and in vitro characterization of this novel nanosystem.Methods: Using established protocol and analytical and spectroscopy techniques we were able to synthesized dendrons with strictly designed properties. Engaging biophysical methods (hydrodynamic diameter and zeta potential measurements, analysis of spectral properties, transmission electron microscopy) we confirmed assembling of our nanosystem. A set of in vitro techniques was used for determination ROS generation, (ABDA and H2DCFDA probes), cell viability (MTT assay) and cellular uptake (flow cytometry and confocal microscopy).Results: Encapsulation of rose bengal inside dendrimersomes enhances cellular uptake, intracellular ROS production and concequently, the phototoxicity of this photosensitizer.Conclusion: Triazine-carbosilane dendrimersomes show high capacity as drug carriers for anticancer photodynamic therapy.Graphical Abstract: Keywords: dendrons, amphiphiles, carbosilane, photodynamic therapy, rose bengal, dendrimersomes

Sara Alonso-Álvarez,1 Emilia Pardal,2 Diego Sánchez-Nieto,3 Miguel Navarro,4 Maria Dolores Caballero,1 Maria Victoria Mateos,1 Alejandro Martín1 1Hematology Department, IBSAL-CIC-USAL, Hospital Universitario de Salamanca, Salamanca, Spain; 2Hematology Department, Hospital Virgen del Puerto, Plasencia, Spain; 3Pharmacy Department, Hospital Universitario de Salamanca, Salamanca, Spain; 4Oncology Department, Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain Abstract: Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin®. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma. In patients with relapsed or refractory multiple myeloma, plitidepsin activity seems to be enhanced after addition of dexamethasone while remaining well tolerated, and a Phase III trial comparing plitidepsin plus dexamethasone vs dexamethasone alone is underway. Additional studies are required to better define the role of plitidepsin in combination with other active agents in these indications. Results of plitidepsin activity in other hematological malignancies or solid tumors have been disappointing so far. Further studies analyzing its mechanisms of action and potential biomarkers will help select patients who may benefit most from this drug. In this review, we critically analyze the published studies on plitidepsin in hematological malignancies and solid tumors and discuss its current role and future perspectives in treating these malignancies. We also review its design, pharmaceutical data, and mechanism of action. Keywords: aplidin, plitidepsin, lymphoma, myeloma, melanoma

Juan Miguel Sánchez-Nieto,1,2 Rubén Andújar-Espinosa,3 Roberto Bernabeu-Mora,1,2 Chunshao Hu,1 Beatriz Gálvez-Martínez,1 Andrés Carrillo-Alcaraz,1 Carlos Federico Álvarez-Miranda,3 Olga Meca-Birlanga,1 Eva Abad-Corpa4 1Division of Pneumology, Hospital Morales Meseguer, 2University of Murcia, 3Division of Pneumology, Hospital Arrixaca, Murcia, 4Department of Professional Development Unit, Murcia, Spain Background: Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD.Methods: Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E) department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality.Results: After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04) and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40.4%) versus 20 (52.6%) (P=0.26), and those who went to A&E, at 9 (19.1%) versus 14 (36.8%) (P=0.06), due to exacerbation of COPD were also lower in this group. Intake of antibiotics was higher in the intervention group, whereas use of glucocorticoids was slightly lower, though there were no significant differences (P=0.30). There were also no differences between groups in the length of hospital stay (P=0.154) or overall mortality (P=0.191).Conclusion: The implementation of a self-management program for patients with advanced COPD reduced exacerbations that required hospital care. Keywords: self-management, COPD, severe exacerbations

Roberto Bernabeu-Mora,1,2 Françesc Medina-Mirapeix,2 Eduardo Llamazares-Herrán,3 Gloria García-Guillamón,2 Luz María Giménez-Giménez,2 Juan Miguel Sánchez-Nieto1,4 1Division of Pneumology, Hospital Morales Meseguer, 2Department of Physical Therapy, University of Murcia, Murcia, 3Department of Physical Therapy, Alcala University, Alcala de Henares, 4Department of Intern Medical, University of Murcia, Murcia, Spain Background: Limited mobility is a risk factor for developing chronic obstructive pulmonary disease (COPD)-related disabilities. Little is known about the validity of the Short Physical Performance Battery (SPPB) for identifying mobility limitations in patients with COPD. Objective: To determine the clinical validity of the SPPB summary score and its three components (standing balance, 4-meter gait speed, and five-repetition sit-to-stand) for identifying mobility limitations in patients with COPD.Methods: This cross-sectional study included 137 patients with COPD, recruited from a hospital in Spain. Muscle strength tests and SPPB were measured; then, patients were surveyed for self-reported mobility limitations. The validity of SPPB scores was analyzed by developing receiver operating characteristic curves to analyze the sensitivity and specificity for identifying patients with mobility limitations; by examining group differences in SPPB scores across categories of mobility activities; and by correlating SPPB scores to strength tests.Results: Only the SPPB summary score and the five-repetition sit-to-stand components showed good discriminative capabilities; both showed areas under the receiver operating characteristic curves greater than 0.7. Patients with limitations had significantly lower SPPB scores than patients without limitations in nine different mobility activities. SPPB scores were moderately correlated with the quadriceps test (r>0.40), and less correlated with the handgrip test (r

Alberto Ortiz,1,2 Maria Dolores Sanchez-Niño1,2 1Department of Nephrology, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autónoma de Madrid, 2Department of Nephrology, Instituto Reina Sofia de Investigación Nefrológica, Madrid, Spain We read with interest the report by Goláň et al on the “Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease”.1 Based on the reported results, the authors conclude that no efficacy or safety differences were found when the approved every-other-week (EOW) dosage of agalsidase alfa was increased to weekly administration. However, the key question is whether the study, as designed and performed, could have had a different outcome. View original article by Goláň et al.

Bernabeu-Mora R, Medina-Mirapeix F, Llamazares-Herrán E, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:619–2626. Page 2626, Acknowledgments section, the text “The authors wish to thank the patients and personnel of the hospital unit for their cooperation during the course of this study. The study was supported by medical manager of AstraZeneca Pharmaceutical Spain, S.A. and Maite Pérez.” Should read “The authors wish to thank the patients and personnel of the hospital unit for their cooperation during the course of this study. The study was supported by medical manager AstraZeneca Pharmaceutical Spain, S.A. Maite Pérez, Pfizer and Menarini.”Read the original article

Abstract Background Existing incidence estimates of heroin use are usually based on one information source. This study aims to incorporate more sources to estimate heroin use incidence trends in Spain between 1971 and 2005. Methods A multi-state model was constructed, whereby the initial state “heroin consumer” is followed by transition to either “admitted to first treatment” or to “left heroin use” (i.e. permanent cessation or death). Heroin use incidence and probabilities of entering first treatment ever were estimated following a back-calculation approach. Results The highest heroin use incidence rates in Spain, around 1.5 per 1,000 inhabitants aged 10–44, occurred between 1985 and 1990; subdividing by route of administration reveals higher incidences of injection between 1980 and 1985 (a mean of 0.62 per 1.000) and a peak for non-injectors in 1990 (0.867 per 1,000). Conclusions A simple conceptual model for heroin users’ trajectories related to treatment admission, provided a broader view of the historical trend of heroin use incidence in Spain.