Acute coronary syndrome and recurrent colitis as immune-related adverse events in a lung cancer patient.

Immune checkpoint inhibitors have become a target for pharmacological research in lung cancer. Immune-related adverse events (irAEs) such as pneumonitis, colitis, hepatitis and endocrinopathies have been well characterized in immune checkpoint inhibitors, but coronary toxicities, like acute coronary syndrome, are poorly described. Herein, we report a possible acute coronary syndrome as immune-related adverse event in a lung cancer patient.

Epidemiological aspects and prevalence study of nosocomial infections in a general hospital of specialties: retrospective analysis 2012-2017.

Nosocomial infections (NIs) currently represent one of the main health problems for both professionals and health authorities. These continue to cause high mortality, which has led to its study and the development of prevention measures to reduce the impact and minimise the incidence. OBJECTIVE: Analysis of the epidemiological aspects of NIs in a tertiary hospital. MATERIALS AND METHODS: A5-year retrospective study in which NIs verified at admission, their prevalence, associated risk factors and their location were analysed and classified. The data were collected through cross sections for hospitalisation episodes, using standardised forms for them issued by the Spanish Society of Preventive Medicine and Public Health. RESULTS: 2905 episodes of hospitalised patients were analysed, where 52.94% were men. The NI acquired in the centre was the most prevalent of all registered, having registered in the last year 53 cases. The infections acquired in the study income remained stable throughout the study, although there was a slight decrease in the last two years. CONCLUSIONS: The multidisciplinary nature of the NIs allows to improve their approach, reducing the harmful effects on health.

ICAM3-Fc Outperforms Receptor-Specific Antibodies Targeted Nanoparticles to Dendritic Cells for Cross-Presentation.

Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to the efficient induction of anti-tumour immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins, which acts as the natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.

Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice.

Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA) was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS) and Interferon-gamma (IFN-γ). TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE), 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes in Response to Omega-3 Supplementation: A Dose-Response Pilot Study.

INTRODUCTION: Supplementation of Omega-3 fatty acids (n-3FA) in athletes is related to the anti-inflammatory and/or antioxidant effect and consequently its action on all the processes of tissue restoration and adaptation to physical stress. OBJECTIVE: Evaluate the Omega-3 Index (O3Ix) response, in red blood cells, to supplemental EPA + DHA intake in the form of high purity and stable composition gums (G), in elite summer athletes. METHOD: Twenty-four summer sport athletes of both sexes, pertaining to the Olympic Training Center in Spain, were randomized to two groups (2G = 760 or 3G = 1140 mg of n-3 FA in Omegafort OKids, Ferrer Intl.) for 4 months. Five athletes and four training staff volunteers were control group. RESULTS: The O3Ix was lower than 8% in 93.1% of all the athletes. The supplementation worked in a dose-dependent manner: 144% for the 3G dose and 135% for the 2G, both p < 0.001, with a 3% significant decrease of Omega-6 FAs. No changes were observed for the control group. CONCLUSIONS: Supplementation with n-3FA increases the content of EPA DHA in the red blood cells at 4 months in a dose-dependent manner. Athletes with lower basal O3Ix were more prone to increment their levels. The study is registered with Protocol Registration and Results System (ClinicalTrials.gov) number NCT02610270.

Effect of TLR ligands co-encapsulated with multiepitopic antigen in nanoliposomes targeted to human DCs via Fc receptor for cancer vaccines.

Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated. Specific uptake in vitro of LHRH-TT liposomes targeted to the FcRs of human DCs was enhanced. DC maturation/activation, cytokine production and lymphocyte activation were consistently higher in targeted than non-targeted liposomes. Similar increase was observed as more adjuvants were administrated. Targeting to specific receptor and co-encapsulation of several TLR adjuvants are essential factors for the immune response in peptide based liposome vaccine.

Controlled release of antigen and Toll-like receptor ligands from PLGA nanoparticles enhances immunogenicity.

AIM: Dendritic cells rapidly capture nanoparticles and induce a potent cellular immune response. It is yet unknown whether the immunological response induced by slow release of encapsulated versus soluble antigen and adjuvant is superior. MATERIALS & METHODS: The kinetics of poly(lactic-co-glycolic acid) PLGA nanoparticles antigen release was studied by the DQ-bovine serum albumin (BSA) self-quenching antigen model. The immunological response induced was evaluated by means of dendritic cell activation/maturation markers, cytokine production and their ability to drive antigen-specific T-cell proliferation. RESULTS & CONCLUSION: PLGA-encapsulated antigen and adjuvant showed an enhanced T-cell response when compared with soluble vaccine components by increasing antigenicity and adjuvanticity. Although the kinetic profile followed the same pattern, encapsulation increased strength and duration of the response.

Targeting the Brain with Nanomedicine.

Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity.

Primeras experiencias de monitorización de vancomicina en un Hospital General de Especialidades / First experiences of monitoring of vancomycin in a General Hospital of Specialties

Introducción: vancomicina es un antibiótico eficaz para el tratamiento de infecciones por gérmenes grampositivos, sin embargo la toxicidad renal asociada a su uso, ha relegado su utilización a líneas secundarias de uso. Este hecho ha consolidado el tratamiento empírico con antibióticos más caros. Objetivo: analizar los datos de monitorización de vancomicina y valorar la eficiencia frente al uso de otros antibióticos. Método: estudio observacional donde se analiza la monitorización farmacocinética de vancomicina y la eficiencia de una Unidad de Farmacocinética Clínica, con una población de 137 pacientes ingresados en un hospital general de especialidades. Resultados: la utilización de vancomicina en primera intención, supuso un ahorro de 16.472,82 € respecto al uso de daptomicina y de 83.039,83 € respecto al de linezolid. No obstante, el 18% de nuestra muestra no pudo ser tratado con vancomicina, lo que hace necesario disponer de otros fármacos

Introduction: vancomycin is an effective antibiotic for the treatment of infections due to Gram-positive germs, however renal toxicity associated with its use, has relegated its use to use secondary lines. This fact has consolidated the empirical treatment with more expensive antibiotics. Objective: to analyze the data of monitoring of vancomycin and rating the efficiency facing the use of other antibiotics. Materials and methods: observational study where discusses monitoring pharmacokinetics of Vancomycin and a unit of pharmacokinetics clinical efficiency, with a population of 137 patients admitted to a general hospital specialties. Results: the use of Vancomycin in first intention meant a savings of € 16.472,82 regarding the use of € 83.039,83 the linezolid and daptomycin. However, 18% of our sample not could be treated with Vancomycin, making it necessary to have other drugs

Análisis y evaluación de resultados tras la implantación de un programa de prescripción electrónica asistida en un hospital de tercer nivel / Analysis and evaluation of results following the implementation of a programme of e-prescribing in a tertiary hospital

Introducción: la Prescripción Electrónica Asistida (PEA), constituye en la actualidad una herramienta útil en el proceso de hospitalización. La supresión de la prescripción y/o transcripción manuscrita, ha conseguido minimizar los errores relacionados con la medicación, mitigando la constante preocupación que supone la seguridad del paciente. Objetivo: analizar los datos de intervención farmacéutica registrados tras la implantación de un software de prescripción electrónica y la seguridad que confiere al usuario. Material y método: estudio retrospectivo de cinco meses de duración, en el que se revisaron las historias clínicas electrónicas de prescripción, describiendo los errores de medicación detectados y el número de intervenciones farmacéuticas realizadas. Resultados: sobre un total de 27.533 validaciones, fueron realizadas 4.917 intervenciones farmacéuticas (IF), lo que supone 32,78 errores de medicación/día y 0,95 errores/paciente

Introduction: the Electronically Assisted Prescription (EAP) is now a useful tool in the process of hospitalization. The removal of the prescription or transcript handwritten, has managed to minimize errors related to medication, mitigating the constant concern involving the safety of the patient. Objective: to analyze data pharmaceutical intervention reported following implementation of a software for e-prescribing and the security that gives the user. Materials and methods: retrospective study of five months duration, which reviewed the electronic medical records of prescription, describing medication errors that are detected and the number of pharmaceutical interventions carried out. Results: out of a total of 27.533 validations, were performed 4.917 pharmaceutical interventions (IF), which represents 32.78 medication errors per day and 0.95 errors per patient

Combinatorial prospects of nano-targeted chemoimmunotherapy.

Despite the significant increase in our knowledge on cancer initiation and progression, and the development of novel cancer treatments, overall patient survival rates have thus far only marginally improved. However, it can be expected that lasting tumor control will be attainable for an increasing number of cancer patients in the foreseeable future, which is likely to be achieved by combining cancer chemotherapy with anticancer immunotherapy. A plethora of new cancer chemotherapy reagents are expected to become accessible to the clinic in the coming years which can then be used for efficient tumor debulking and aid in antigen exposure to the immune system. Durable remission and the eradication of micrometastases are likely to be achieved with specialized monoclonal antibodies and therapeutic cancer vaccines that modulate the immune system to overcome immunosuppression and kill distant cancer cells. Moreover, the method of drug delivery to tumors, stromal and immune cells is expected to shift largely from conventional 'free' drug molecules to encapsulated in targeted nano-vehicles, therapeutics often referred to or considered part of "nanomedicine". Several biocompatible nano-vehicles, such as metal-nanoparticles, biodegradable-nanoparticles, liposomes or dendrimers are potential candidates for targeted drug delivery but may also serve additional purposes. A dexterous combination of nanomedicine, cancer immunotherapy and chemotherapeutic engineering are likely to become the basis for new hope in the form of targeted cancer therapies that could attack tumors early in their development. One can envision nano-vehicles that would selectively deliver effective doses of chemotherapeutic agents to cancer cells while leaving healthy cells untouched. Furthermore, given that after chemotherapeutic treatment there often remains a limited number of chemo-resistant tumor cells, which go on to drive tumor progression, nano-vehicles could also be engineered to provoke an appropriate immune response to destroy these cells. Here, we discuss the potential of the combinatorial role of cancer chemotherapy, cancer immunotherapy and the prospective of nanotechnology for the targeted delivery of chemoimmunotherapeutic agents.

Características clínico-epidemiológicas de pacientes hospitalizados en tratamiento con antibióticos de uso restringido en un hospital de segundo nivel: Análisis de prescripción / Clinical-epidemiological characteristics of inpatients in antibiotic treatment of restricted use in a second level hospital: analysis of prescription

Introducción. La inadecuada utilización de los antibióticos restringidos (ATBr) en el entorno hospitalario, constituyen en la actualidad un importante problema de salud. Su uso indiscriminado y la ausencia de supervisión por parte de especialistas en enfermedades infecciosas, están contribuyendo a una acelerada selección de cepas resistentes, lo que se traduce en un cada vez más reducido arsenal terapéutico. Objetivo. Analizar la correcta o incorrecta indicación de los antibióticos restringidos en nuestro hospital, de acuerdo al diagnóstico principal. Material y método. Estudio observacional y descriptivo de una serie de 126 casos consecutivos analizados a lo largo de seis meses, en el que se revisaron tanto historias clínicas como solicitudes de antibióticos restringidos. Resultados. El 61,11% de los pacientes a los que se les prescribió un ATBr habían recibido tratamiento previo y en un 19,84% los ATBr fueron prescritos de inicio. El 73% de las prescripciones eran inadecuadas o estaban incompletas

Introduction. The improper use of restricted antibiotics (ATBr) in the hospital environment, currently constitute a major health problem. Their indiscriminate use and the absence of oversight by specialists in infectious diseases, are contributing to an accelerated selection of resistant strains, which translates into an increasingly smaller therapeutic arsenal. Objective. To analyze the right or wrong indication of restricted antibiotics in our hospital, according to the primary diagnosis. Material and methods. Observational and descriptive study of a series of 126 consecutive cases analyzed over six months, in which we reviewed both stories clinics as requests for restricted antibiotics. Results. The 61.11% of patients who are prescribed an ATBr had been treated prior and a 19.84% the ATBr were prescribed home. The 73% remaining prescriptions were inadequate or incomplete

Resultados en la prescripción electrónica de nutriciones parenterales tras la implantación de un programa informático. Análisis de costes y prescripción / Results in the parenteral nutritions electronic prescription following implementation of a computer program. Cost analysis and prescription

Introducción. Cada vez son más los hospitales que incorporan en su tecnología software informáticos capaces de elaborar una nutrición eficaz, segura y ajustada a las necesidades de los pacientes con el fin de minimizar errores. Sin embargo, estos programas no siempre disponen de un manejo intuitivo, lo que en ocasiones, pueden comportar diversas dificultades que los haga estar infrautilizados y en consecuencia, el número de prescripciones puede verse disminuido. Objetivo: Evaluar la reducción en la prescripción de nutriciones parenterales y el impacto económico que ha supuesto en nuestro centro, tras la implantación de un software informático de prescripción electrónica para nutriciones parenterales. Material y métodos. Se utilizó un software informático de Fresenius-Kabi España (v. 1.8/2011) como base de datos, para clasificar las NP prescritas durante los últimos 24 meses, teniendo en cuenta la implantación de la herramienta informática. Este procedimiento se usó para determinar la disminución en la prescripción de nutriciones. Resultados. Durante el año 2013 se prescribieron un total de 3.530 nutriciones parenterales, mientras que en el mismo periodo de 2014, las nutriciones prescritas fueron 2.622. Esta diferencia de 908 prescripciones, supuso un ahorro económico de 22.230,03 Euros

Introduction. Increasingly hospitals that incorporate in its software technology computer capable of developing a nutrition effective, safe and adjusted to the needs of patients in order to minimize errors. However, these programs do not always have an intuitive, sometimes, may lead to difficulties making them to be underused and as a result, the number of prescriptions will be decreased. Objective. To evaluate the reduction in prescription of parenteral nutritions and the economic impact that has been in our centre, the introduction of computer software for electronic prescription for parenteral nutritions. Material and method. A computer software of Fresenius-Kabi Spain (v. 1.8/2011) as the database, was used to classify the NP prescribed during the past 24 months, taking into account the implementation of the computer tool. This procedure was used to determine the reduction in prescription of nutritions. Results. During the year 2013 were prescribed a total of 3.530 parenteral nutritions, while in the same period in 2014, prescribed nutritions were 2.622. This difference of 908 prescriptions meant a savings of 22.230,03 Euros

Reacción de hipersensibilidad a carboplatino no reversible mediante protocolo de desensibilización / Carboplatino hypersensitivity reaction by protocol no reversible desensitization

Los compuestos de platino son ampliamente utilizados en diferentes tumores, siendo carboplatino el indicado en carcinoma de ovario. La principal toxicidad limitante de dosis de carboplatino es la trombopenia, sin embargo, en ocasiones presenciamos reacciones de hipersensibilidad que, aunque no es un hecho demasiado frecuente (8-16%), sí puede ser grave. Por ello, han sido desarrollados protocolos de desensibilización. Comunicamos el caso de una paciente intervenida quirúrgicamente de un carcinoma seroso papilar de ovario (estadio IIIC) y que posteriormente recibió quimioterapia adyuvante con carboplatino y paclitaxel. Tras veintidós meses de intervalo libre de enfermedad, mostró recaída abdominal irresecable, por lo que se instauró de nuevo tratamiento con carboplatino y paclitaxel. Durante la administración del segundo ciclo, manifestó reacción grave de hipersensibilidad a carboplatino. Se intentó esquema de desensibilización sin éxito, no pudiendo continuar con dicho tratamiento y obligando a iniciar segunda línea con trabectedina y adriamicina liposomal pegilada (AU)

Platinum compounds are widely used in different tumors, being carboplatin indicated in ovarian carcinoma. The main carboplatin-dose limiting toxicity is the thrombocytopenia, however, sometimes we have seen hypersensitivity reactions that, although it is not a fact too often (8-16%), can be severe. For this reason, desensitization protocols have been developed. We report the case of a patient intervened surgically from a papillary serous carcinoma of ovary (stage IIIC) and who later received adjuvant chemotherapy with carboplatin and paclitaxel. After twenty-two months of disease-free interval, she showed unresectable abdominal relapse, so it was again treated with carboplatin and paclitaxel. During the administration of the second cycle, said severe hypersensitivity reaction to carboplatin. Attempted to desensitization unsuccessfully, can not continue with this treatment scheme and forcing to start second line with trabectedin and pegylated liposomal adriamycin (AU)

Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study.

Here we demonstrated the importance of targeting antigens (Ags) to dendritic cell (DC) receptors to achieve an efficient cytotoxic T cell response which was associated with a strong activation of DC. Pegylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate ovalbumin (OVA) as a model Ag. This PLGA complex, together with Toll like receptor (TLR) 3 and 7 ligands, was then targeted to distinct DC cell-surface molecules. These cell-surface molecules, including CD40, a TNF-α family receptor, DEC-205, a C-type lectin receptor and CD11c, an integrin receptor, were targeted by means of specific monoclonal antibodies (mAbs) coupled to the NP. The efficiency of these different targeting strategies to activate DC and elicit a potent CD8(+) T cell response was studied. PLGA-(Ag/TLR3+7L) NP was more efficiently targeted to and internalized by DC in vitro compared to the control non-targeted NP. We observed a small but significantly improved internalization of CD40-targeted NP compared to DEC-205 or CD11c targeted NP. In contrast to non-targeted NP, all targeted NPs equally stimulated IL-12 production and expression of co-stimulatory molecules by DC, inducing strong proliferation and IFN-y production by T cells in vitro. Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T cell responses. However, all targeted NP vaccines showed an equal capacity to prime cytotoxic CD8+ T cells, which subsequently were able to induce targeted cell lysis. In conclusion, delivery of NP-vaccines to DC by targeting via cell-surface molecules leads to strong enhancement of vaccine potency and induction of T cell responses compared to non-specific delivery of NP to DC.

Liposomes containing NY­ESO­1/tetanus toxoid and adjuvant peptides targeted to human dendritic cells via the Fc receptor for cancer vaccines.

AIM: To improve the immunological response against tumors, a vaccine based on nanoliposomes targeted to the Fcg-receptor was developed to enhance the immunogenicity of tumor-associated antigens (TAAs). MATERIALS & METHODS: Using human dendritic cells in vitro, a fragment of the TAA NY-ESO-1 combined with a T-helper peptide from the tetanus toxoid encapsulated in nanoliposomes was evaluated. In addition, peptides Palm-IL-1 and MAP-IFN-g were coadministered as adjuvants to enhance the immunological response. RESULTS: Coadministration of Palm-IL-1 or MAP-IFN-g peptide adjuvants and the hybrid NY-ESO-1-tetanus toxoid (soluble or encapsulated in nanoliposomes without targeting) increased immunogenicity. However, the most potent immunological response was obtained when the peptide adjuvants were encapsulated in liposomes targeted to human dendritic cells via the Fc receptor. CONCLUSION: This targeted vaccine strategy is a promising tool to activate and deliver antigens to dendritic cells, thus improving immunotherapeutic response in situations in which the immune system is frequently compromised, as in advanced cancers.

Enhancing immunogenicity and cross-reactivity of HIV-1 antigens by in vivo targeting to dendritic cells.

Current retroviral treatments have reduced AIDS to a chronic disease for most patients. However, given drug-related side effects, the emergence of drug-resistant strains and the persistence of viral replication, the development of alternative treatments is a pressing need. This review focuses on recent developments in HIV immunotherapy treatments, with particular emphasis on current vaccination strategies for optimizing the induction of an effective immune response by the recruitment of dendritic cells. In addition to cell-based therapies, targeted strategies aiming to deliver synthetic HIV peptides to dendritic cell-specific receptors in vivo will be discussed.

Targeting nanoparticles to dendritic cells for immunotherapy.

Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in vivo represents a promising strategy to enhance immune responses. Delivering particulate vaccines specifically to DCs and preventing nonspecific uptake by other endocytotic cells are challenging. Size represents a critical parameter determining whether particulate vaccines can penetrate lymph nodes and reach resident DCs. Specific delivery is further enhanced by actively targeting DC-specific receptors. This chapter discusses the rationale for the use of particle-based vaccines and provides an overview of antigen-delivery vehicles currently under investigation. In addition, we discuss how vaccine delivery systems may be developed, focusing on liposomes, PLGA polymers, and gold nanoparticles, to obtain safe and efficacious vaccines.