New bladder cancer non-invasive surveillance method based on voltammetric electronic tongue measurement of urine.

Bladder cancer (BC) is the sixth leading cause of death by cancer. Depending on the invasiveness of tumors, patients with BC will undergo surgery and surveillance lifelong, owing the high rate of recurrence and progression. In this context, the development of strategies to support non-invasive BC diagnosis is focusing attention. Voltammetric electronic tongue (VET) has been demonstrated to be of use in the analysis of biofluids. Here, we present the implementation of a VET to study 207 urines to discriminate BC and non-BC for diagnosis and surveillance to detect recurrences. Special attention has been paid to the experimental setup to improve reproducibility in the measurements. PLSDA analysis together with variable selection provided a model with high sensitivity, specificity, and area under the ROC curve AUC (0.844, 0.882, and 0.917, respectively). These results pave the way for the development of non-invasive low-cost and easy-to-use strategies to support BC diagnosis and follow-up.

Resultados de morbimortalidad en cáncer colorrectal en paciente quirúrgico frágil. Implementación de un Área de Atención al Paciente Quirúrgico Complejo / Colorectal carcinoma in the frail surgical patient. Implementation of a Work Area focused on the Complex Surgical Patient improves postoperative outcome

INTRODUCCIÓN: La edad avanzada y la presencia de comorbilidades repercuten en la morbimortalidad postoperatoria del paciente quirúrgico frágil. El objetivo de este estudio es valorar los resultados de morbimortalidad tras cirugía por cáncer colorrectal en el paciente quirúrgico frágil tras la implementación de un Área de Atención al paciente Quirúrgico Complejo (AAPQC). MÉTODOS: Estudio retrospectivo con recogida prospectiva de datos. Un total de 91 pacientes consecutivos considerados como frágiles (ASAIV o ASAIII con Barthel < 80 i/o Pfeiffer>3) fueron intervenidos entre 2013 y 2015 con diagnóstico de cáncer colorrectal con intención curativa. Grupo I (AAPQC): 35 pacientes incluidos en AAPQC durante 2015. Grupo II (No AAPQC): 56 pacientes intervenidos entre 2013 y 2014 previa implementación del AAPQC. Se analizó homogeneidad de grupos, complicaciones, estancia media, mortalidad, reintervenciones, reingresos y costes en función del GRD. RESULTADOS: No se encontraron diferencias significativas en edad, sexo, ASA, índex de masa corporal, estadio tumoral y tipo de intervención quirúrgica entre los dos grupos. Las complicaciones mayores (Clavien-DindoIII-IV) (11,4% vs. 28,5%, p = 0,041), la estancia media (12,6 ± 6 días vs. 15,2 ± 6 días, p = 0,043), los reingresos (11,4% vs. 28,3%, p = 0,041) y el peso específico del episodio (3,29 ± 1 vs 4,3 ± 1, p = 0,008) fueron significativamente menores en el grupo AAPQC. No hubo diferencias en re intervenciones (6,2% vs. 5,3%) ni mortalidad (6,2% vs 7,1%). El 96,9% de pacientes del grupo I manifestó una atención y calidad de vida satisfactoria. CONCLUSIONES: La implementación de una AAPQC en pacientes frágiles que deben ser intervenidos de cáncer colorrectal comporta una reducción de las complicaciones, estancia y reingresos, y es una medida coste-efectiva

INTRODUCTION: Advanced age and comorbidity impact on post-operative morbi-mortality in the frail surgical patient. The aim of this study is to assess the impact of a comprehensive, multidisciplinary and individualized care delivered to the frail patient by implementation of a Work Area focused on the Complex Surgical Patient (CSPA). METHODS: Retrospective study with prospective data collection. Ninety one consecutive patients, classified as frail (ASAIII or IV, Barthel<80 and/or Pfeiffer>3) underwent curative radical surgery for colorectal carcinoma between 2013 and 2015. GroupI: 35 patients optimized by the CSPA during 2015. Group II: 56 No-CSPA patients, treated prior to CSPA implementation, during 2014-2015. Group homogeneity, complication rate, length of stay, reoperations, readmissions, costs and overall mortality were analyzed and adjusted by Diagnosis-Related Group (DRG). RESULTS: There were no statistically significant differences in term of age, gender, ASA classification, body mass index, tumor staging and type of surgical intervention between the two groups. Major complications (Clavien-DindoIII-IV) (12.5% vs. 28.5%, P = .04), hospital stay (12.6 ± 6 days vs. 15.2 ± 6 days, P = 0.041), readmissions (12.5% vs. 28.3%, P < 0.041), and patient episode cost weighted according to DRG (3.29 ± 1 vs. 4.3 ± 1, P = 0.008) were statistically inferior in Group CSPA. There were no differrences in reoperations (6.2% vs. 5.3%) or mortality (6.2% vs. 7.1%). 96.9% of patients of Group I manifested having received a satisfactory attention and quality of life. CONCLUSIONS: Implementation of a CSPA, delivering surgical care to frail colorectal cancer patients, involves a reduction of complications, length of stay and readmissions, and is a cost-effective arrangement

Colorectal carcinoma in the frail surgical patient. Implementation of a Work Area focused on the Complex Surgical Patient improves postoperative outcome. / Resultados de morbimortalidad en cáncer colorrectal en paciente quirúrgico frágil. Implementación de un Área de Atención al Paciente Quirúrgico Complejo.

INTRODUCTION: Advanced age and comorbidity impact on post-operative morbi-mortality in the frail surgical patient. The aim of this study is to assess the impact of a comprehensive, multidisciplinary and individualized care delivered to the frail patient by implementation of a Work Area focused on the Complex Surgical Patient (CSPA). METHODS: Retrospective study with prospective data collection. Ninety one consecutive patients, classified as frail (ASAIII or IV, Barthel<80 and/or Pfeiffer>3) underwent curative radical surgery for colorectal carcinoma between 2013 and 2015. GroupI: 35 patients optimized by the CSPA during 2015. GroupII: 56 No-CSPA patients, treated prior to CSPA implementation, during 2014-2015. Group homogeneity, complication rate, length of stay, reoperations, readmissions, costs and overall mortality were analyzed and adjusted by Diagnosis-Related Group (DRG). RESULTS: There were no statistically significant differences in term of age, gender, ASA classification, body mass index, tumor staging and type of surgical intervention between the two groups. Major complications (Clavien-DindoIII-IV) (12.5% vs. 28.5%, P=.04), hospital stay (12.6±6days vs. 15.2±6days, P=0.041), readmissions (12.5% vs. 28.3%, P<0.041), and patient episode cost weighted according to DRG (3.29±1 vs. 4.3±1, P=0.008) were statistically inferior in Group CSPA. There were no differrences in reoperations (6.2% vs. 5.3%) or mortality (6.2% vs. 7.1%). 96.9% of patients of GroupI manifested having received a satisfactory attention and quality of life. CONCLUSIONS: Implementation of a CSPA, delivering surgical care to frail colorectal cancer patients, involves a reduction of complications, length of stay and readmissions, and is a cost-effective arrangement.

MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications.

Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with 99mTc (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice.

Pseudorotaxane capped mesoporous silica nanoparticles for 3,4-methylenedioxymethamphetamine (MDMA) detection in water.

Mesoporous silica nanoparticles loaded with fluorescein and capped by a pseudorotaxane, formed between a naphthalene derivative and cyclobis(paraquat-p-phenylene) (CBPQT4+), were used for the selective and sensitive fluorogenic detection of 3,4-methylenedioxymethamphetamine (MDMA).

Acetylcholinesterase-capped Mesoporous Silica Nanoparticles Controlled by the Presence of Inhibitors.

Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamine B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE's active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rhodamine B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE's active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon.

Acetylcholinesterase-Capped Mesoporous Silica Nanoparticles That Open in the Presence of Diisopropylfluorophosphate (a Sarin or Soman Simulant).

Mesoporous silica nanoparticles loaded with rhodamine B and capped with acetylcholinesterase are able to be selectively opened and deliver their cargo in the presence of nerve agent simulant diisopropyl fluorophosphate (DFP).

Detection of prostate cancer using a voltammetric electronic tongue.

A simple method based on the multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% were obtained to distinguish the urine from cancer patients and the urine from non-cancer patients.

Gated Materials for On-Command Release of Guest Molecules.

Multidisciplinary research at the forefront of the field of hybrid materials has paved the way to the development of endless examples of smart devices. One appealing concept in this fertile field is related to the design of gated materials. These are constructed for finely tuning the delivery of chemical or biochemical species from voids of porous supports to a solution in response to predefined stimuli. Such gated materials are composed mainly of two subunits: (i) a porous inorganic support in which a cargo is loaded and (ii) certain molecular or supramolecular entities, generally grafted onto the external surface, which can control mass transport from pores. On the basis of this concept, a large number of imaginative examples have been developed. This review intends to be a comprehensive analysis of papers published until 2014 on hybrid mesoporous gated materials. The molecules used as gates, the opening mechanisms, and controlled release behavior are detailed. We hope this review will not only help researchers who work in this field but also may open the minds of related ones to develop new advances in this fertile research area.

Gated Silica Mesoporous Materials in Sensing Applications.

Silica mesoporous supports (SMSs) have a large specific surface area and volume and are particularly exciting vehicles for delivery applications. Such container-like structures can be loaded with numerous different chemical substances, such as drugs and reporters. Gated systems also contain addressable functions at openings of voids, and cargo delivery can be controlled on-command using chemical, biochemical or physical stimuli. Many of these gated SMSs have been applied for drug delivery. However, fewer examples of their use in sensing protocols have been reported. The approach of applying SMSs in sensing uses another concept-that of loading pores with a reporter and designing a capping mechanism that is selectively opened in the presence of a target analyte, which results in the delivery of the reporter. According to this concept, we provide herein a complete compilation of published examples of probes based on the use of capped SMSs for sensing. Examples for the detection of anions, cations, small molecules and biomolecules are provided. The diverse range of gated silica mesoporous materials presented here highlights their usefulness in recognition protocols.

Oligonucleotide-capped mesoporous silica nanoparticles as DNA-responsive dye delivery systems for genomic DNA detection.

New hybrid oligonucleotide-capped mesoporous silica nanoparticles able to detect genomic DNA were designed.

A Chromogenic Probe for the Selective Recognition of Sarin and Soman Mimic DFP.

The synthesis, characterization and sensing features of a novel probe 1 for the selective chromogenic recognition of diisopropylfluorophosphate (DFP), a sarin and soman mimic, in 99:1 (v/v) water/acetonitrile and in the gas phase is reported. Colour modulation is based on the combined reaction of phosphorylation of 1 and fluoride-induced hydrolysis of a silyl ether moiety. As fluoride is a specific reaction product of the reaction between DFP and the -OH group, the probe shows a selective colour modulation in the presence of this chemical. Other nerve agent simulants, certain anions, oxidant species and other organophosphorous compounds were unable to induce colour changes in 1. This is one of the very few examples of a selective detection, in solution and in the gas phase, of a sarin and soman simulant versus other reactive derivatives such as the tabun mimic diethylcyanophosphate (DCNP).

A surfactant-assisted probe for the chromo-fluorogenic selective recognition of GSH in water.

Chromo-fluorogenic detection of GSH versus cysteine in water was accomplished using a pyrylium-stilbene derivative and CTAB micelles.

An electronic tongue designed to detect ammonium nitrate in aqueous solutions.

An electronic tongue has been developed to monitor the presence of ammonium nitrate in water. It is based on pulse voltammetry and consists of an array of eight working electrodes (Au; Pt; Rh; Ir; Cu; Co; Ag and Ni) encapsulated in a stainless steel cylinder. In a first step the electrochemical response of the different electrodes was studied in the presence of ammonium nitrate in water in order to further design the wave form used in the voltammetric tongue. The response of the electronic tongue was then tested in the presence of a set of 15 common inorganic salts; i.e.; NH4NO3; MgSO4; NH4Cl; NaCl; Na2CO3; (NH4)2SO4; MgCl2; Na3PO4; K2SO4; K2CO3; CaCl2; NaH2PO4; KCl; NaNO3; K2HPO4. A PCA plot showed a fairly good discrimination between ammonium nitrate and the remaining salts studied. In addition Fuzzy Art map analyses determined that the best classification was obtained using the Pt; Co; Cu and Ni electrodes. Moreover; PLS regression allowed the creation of a model to correlate the voltammetric response of the electrodes with concentrations of ammonium nitrate in the presence of potential interferents such as ammonium chloride and sodium nitrate.

Design of enzyme-mediated controlled release systems based on silica mesoporous supports capped with ester-glycol groups.

An ethylene glycol-capped hybrid material for the controlled release of molecules in the presence of esterase enzyme has been prepared. The final organic-inorganic hybrid solid S1 was synthesized by a two-step procedure. In the first step, the pores of an inorganic MCM-41 support (in the form of nanoparticles) were loaded with [Ru(bipy)(3)]Cl(2) complex, and then, in the second step, the pore outlets were functionalized with ester glycol moieties that acted as molecular caps. In the absence of an enzyme, release of the complex from aqueous suspensions of S1 at pH 8.0 is inhibited due to the steric hindrance imposed by the bulky ester glycol moieties. Upon addition of esterase enzyme, delivery of the ruthenium complex was observed due to enzymatic hydrolysis of the ester bond in the anchored ester glycol derivative, inducing the release of oligo(ethylene glycol) fragments. Hydrolysis of the ester bond results in size reduction of the appended group, therefore allowing delivery of the entrapped cargo. The S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays with HeLa and MCF-7 cell lines, and were found to be associated with lysosomes, as shown by confocal microscopy. However, when S1 nanoparticles were filled with the cytotoxic drug camptothecin (S1-CPT), S1-CPT-treated cells undergo cell death as a result of S1-CPT cell internalization and subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate that induced the release of the camptothecin cargo. These findings point to a possible therapeutic application of these nanoparticles.

Coordinación entre servicios de urgencias. Un modelo eficaz en la planificación sanitaria / Coordination among emergency services. An effective model for healthcare planning

Objetivo: Evaluar, mediante un estudio de intervención con controles históricos, la optimización del traslado de pacientes desde el servicio de urgencias de un hospital de alta complejidad -centro emisor (CE)- a un hospital de menor complejidad -centro receptor (CR)- durante el invierno. Material y método: La intervención consistió en la creación de los siguientes recursos y dispositivos: criterios de selección de pacientes aptos para ser trasladados, sistema exclusivo de comunicación, un horario de traslados, obtención de resultados pendientes de pruebas efectuadas en el CE, una unidad de hospitalización específica en el CR, circuito de altas y prealtas en el CR, normas escritas de coordinación entre la unidad asistencial, la Unidad de Trabajo Social y el Servicio de Farmacia Hospitalaria, hoja de acogida y un circuito de información a las residencias sanitarias. Resultados: Se trasladó a 247 pacientes. Ningún paciente permaneció en el área de urgencias del CR. No hubo ninguna desprogramación de ingresos en el CR. El índice de reingreso a los 30 días fue del 2,4 por ciento. La estancia media en el CR fue de 5,63 días. El índice funcional fue de 0,6; la razón de funcionamiento estándar, 0,6; la diferencia atribuible al funcionamiento, 4,0 y el impacto, 706.Conclusiones: La intervención en el traslado de pacientes desde un servicio de urgencias de un centro de alta complejidad a un centro de menor complejidad, para evitar el colapso del primero, mejora la calidad asistencial de los pacientes trasladados y evita mermar la del hospital receptor (AU)