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Purpose:To compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination(TC) therapy versus ondansetron/dexamethasone double combination(DC) therapy as antiemetic prophylaxis in patients with solid tumors after a moderated emetic regiment of carboplatin AUC≥4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 hour to 15 minutes before chemotherapy. Methods:Single institution prospective study in which assignment to groups was not randomized. Patients receiving carboplatin AUC≥4 enrolled the study. Chemotherapy-induced nausea and vomiting (CINV) was evaluated using MASCC antiemetic tool, in acute (2 test. Results:Two-hundred four completed questionnaires (CQ) were analyzed, 76 belonging to DC and 128 to TC. The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92%, p=0.0109) and delayed phase (97.6% vs 90.5%, p=0.042). Likewise, a higher proportion of TC-treated patients compared to DC, remained nausea-free for the first 24 hours after treatment (90.6% vs 72%, p=0.0005) and after 120 hours (82.3% vs 63.5%, p=0.0031). Comparison of the change in NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5% p=0.70). Conclusions:A triple antiemetic combination should be used in carboplatin AUC≥4 regimens. TC showed superiority in early and delayed CINV control, with no significant differences among different cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospital, before chemotherapy session, instead of at home.

Calidad percibida por el usuario con patología en el sistema músculo-esquelético, de la atención recibida en la Unidad de Fisioterapia. Doctorando: Mª José Llácer Bosch Directores de tesis: Dr. D. José María Tenías Burillo, Dr. D. José Casaña Granell, Dr. D. Felipe Querol Fuentes. Programa de doctorado: Procesos del Envejecimiento: Estrategias Sociosanitarias. Facultat de Fisioterapàpia. Universitat de València. Fecha: 24 de julio de 2017 RESUMEN Introducción Evaluar la satisfacción de los usuarios y la calidad que perciben los pacientes de la atención sanitaria es parte fundamental de la gestión de los servicios de salud y constituye una preocupación de todos los actores que intervienen en el proceso asistencial: pacientes, profesionales, gestores y políticos. Las patologías relacionadas con el sistema músculo-esquelético van a tener una mayor prevalencia en una población envejecida y con una esperanza de de vida mayor, ello supone un aumento de la presión asistencial sobre las Unidades de Fisioterapia al aumentar la demanda de nuestros servicios. Es obvio que el aumento de la carga de trabajo sobre las Unidades de Fisioterapia, repercute en la forma de trabajo del fisioterapeuta de AP que de forma paulatina, ha ido disminuyendo el tiempo que dedica a la atención en función del aumento de la carga asistencial. Este aumento de la presión asistencial, y de las cargas en las Unidades de Fisioterapia, ¿puede estar repercutiendo en los resultados clínicos y funcionales de los patientes? ¿está repercutiendo en la calidad asistencial? ¿la mejoria clinica del paciente, guarda relación con la calidad que perciba? Las Unidades de Fisioterapia realizan un tipo de atención sanitaria diferente y peculiar con respecto a otros servicios sanitarios, por lo que es inviable la utilización de cuestionarios de satisfacción diseñados otros servicios. como urgencias, cirugía o hospitalización. El cuestionario de calidad percibida PEPAP-Q, está diseñado para medir la calidad que percibe el paciente con patología en el sistema músculo-esquelético en las Unidades de Fisioterapia. Se trata de un cuestionario que consta de 23 ítems que analizan 2 áreas y 7 dominios. Diseñando en la Universidad de Murcia bajo la dirección del Dr. Medina-Mirapeix y validado en 2015. Material y Metodo La muestra de este estudio es de 219 sujetos clasificados en 6 grupos en función de la localización de su patología. Para conocer la mejoría clínica de los sujetos se han realizado mediciones y valoraciones del ROM, la fuerza, el dolor al inicio (fase1) y al alta del tratamiento (fase 3). Para conocer la mejoría funcional se han utilizado diferentes cuestionarios funcionales en función de la patología (Womac, Oswestry, NDI, Dash, Constant-Murley, Time Up and Go, Sit To Stand) también en la fase1 y 3. Finalmente, para conocer la calidad percibida por el usuario se ha utilizado el cuestionario PEPAP-Q, medida a las 10-15 sesiones (fase 2), y en caso de recibir un número menor de sesiones, se realizaría en la fase 3. Resultados La muestra (n=219) estuvo compuesta por 71 hombres (32.4%) y 148 mujeres (67.6%), con una media de edad de 59.9 años (DE 14 años; rango de 20 a 87 años). Siendo la media de edad en hombres de 58.1 años y en mujeres de 60.8 años. La muestra de este estudio puntuó bien la calidad que percibió de la Unidad de Fisioterapia donde se le trató, con una puntuación total del PEPAP-Q de 39.89 puntos. Los resultados revelaron que, el dominio mejor valorado fue el dominio que analizó “la seguridad del paciente” (D7), con una media de 5.28 puntos, seguido por el dominio D1 que analizó “la información y educación al paciente” (19.28 puntos), y del dominio D2 “apoyo emocional” (27.31 puntos). Por otro lado, los dominios peor valorados corresponden a la “duración de la atención” D4 (96.18 puntos) y “las interrupciones durante el tratamiento” (58.47 puntos). Respecto a las áreas, nuestra muestra valoró mejor el área 1 “actitudes y comportamiento del fisioterapeuta” (27.82 puntos), y peor al área 2 “ambiente organizacional” (50.03 puntos). Todos los grupos mejoraron, pero los grupos que mayor mejoría clínica obtuvieron fueron los grupos hombro, mano y rodilla. Siendo en los parámetros “recorrido articular” y la “mejoría del dolor” donde hay relación estadística con respecto a la calidad percibida (PEPAP-Q) en dichos grupos. Conclusión La calidad percibida medida a través del cuestionario PEPAP-Q es buena. Con un resultado del 38.89%, donde 0 indicaría ausencia de problemas y 100 todo lo contrario. El área 1 “actitudes y comportamientos del fisioterapeuta”, ha sido el área del cuestionario PEPAP-Q mejor valorada con un resultado de 27.82%. El dominio 4 “duración de la atención”, el dominio 5 “las interrupciones durante el tratamiento” y el dominio 6 “tiempo de espera durante el tratamiento” son los que peores resultados han obtenido del cuestionario PEPAP-Q, con un 96.18%, 58.47% y 44.08% respectivamente. Las variables sociodemográficas (edad, sexo y nivel de estudios), no guardan una relación significativa con la calidad percibida. La mejoría clínica y funcional es positiva en todos los grupos. Los grupos que mayor mejoría clínica y funcional obtienen (hombro, mano y rodilla), son los que mejor puntúan el cuestionario de calidad con una relación significativa en el dominio 2” el apoyo emocional” y, significación negativa con el dominio 4 “duración de la atención” del cuestionario PEPAP-Q. Cuando la información sobre los ejercicios y consejos que debe seguir el paciente en su domicilio es adecuada y está bien programada, la adherencia al tratamiento domiciliario es mayor y guarda relación estadísticamente significativa con el dominio 1 “información y educación” del cuestionario PEPAP-Q.

Recent decades have seen a paradigm shift in the treatment of liver tumours from invasive surgical procedures to minimally invasive image-guided ablation techniques. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a novel, completely non-invasive ablation technique that has the potential to change the field of liver tumour ablation. The image guidance, using MR imaging and MR temperature mapping, provides excellent planning images and real-time temperature information during the ablation procedure. However, before clinical implementation of MR-HIFU for liver tumour ablation is feasible, several organ-specific challenges have to be addressed. In this review we discuss the MR-HIFU ablation technique, the liver-specific challenges for MR-HIFU tumour ablation, and the proposed solutions for clinical translation.

Purpose: Women affected with invasive breast cancer generally undergo sentinel node biopsy (SNB) of the axilla, which is followed by axillary dissection if lymph node metastases are found. This systematic review and meta-analysis aims to evaluate the utility of preoperative axillary ultrasound-guided needle biopsy in terms of staging the axilla and preventing futile SNB. Methods: We systemically searched Pubmed, Embase and Cochrane through March 14, 2011, for studies addressing preoperative assessment of axillary lymph node (ALN) status by axillary ultrasound and biopsy. Eligible studies had to report on biopsy indication and method, and true and false positive and negative outcomes. A pooled estimate was calculated for prevalence of futile SNB (defined as the proportion of patients needing secondary ALN dissection after a negative axillary ultrasound and biopsy) and sensitivity (defined as the proportion of patients with ALN involvement detected by axillary ultrasound and biopsy). Results: Twenty-three studies were included which reported on a total of 6205 procedures. The pooled prevalence of futile SNB was 25% (95% CI = 23% to 27%) and the pooled sensitivity was 51% (95% CI = 43% to 59%). There was substantial heterogeneity across studies for both futile SNB prevalence (I2 = 60.5) and sensitivity (I2 = 93.3), which could not be explained by between-study differences in biopsy technique, inclusion criteria, biopsy indication or study design. Sensitivity was increased in studies with a high prevalence of axillary lymph node metastases. Conclusion: Preoperative axillary ultrasound guided biopsy is a useful step in the process of axillary staging as around fifty percent of breast cancer patients with axillary involvement can be identified pre-operatively and are spared a two step surgical intervention. Still, one in four women with a US biopsy ‘proven’ negative axilla have ALN involvement on SNB and need to undergo completion axillary dissection. New techniques may be able to reduce the prevalence of futile SNB. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-12.

Background: For the management of non-palpable breast cancer, accurate preoperative localization is essential to achieve complete resection with acceptable cosmetic results. ROLL takes advantage of the intratumorally injected radiotracer, that is already used for the sentinel node procedure, to localize the primary tumor during surgery. In a multicenter randomized controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire guided localization, WGL) for preoperative tumor localization. Methods: Women (>18 yrs.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment (BCT) with sentinel node procedure were randomized to ROLL or WGL. Patients allocated to ROLL received an intra-tumoral dose of 120 Mbq Technetium99 nanocolloid. Guided by a gamma detection probe, the surgeon excised the primary tumor and the sentinel node(s). In the WGL group, patients received a similar intra-tumoral or periaureolair dose of technetium in order to allow sentinel node biopsy. Ultrasound or mammography guided insertion of a hooked wire provided surgical guidance for excision of the primary tumor. Primary outcome measure was the proportion of complete tumor excisions (i.e. with negative margins). Furthermore, the proportion of patients requiring re-excision was assessed. Data were analyzed according to intention to treat analysis. Results: Three hundred and fourteen patients with 316 invasive breast cancers were enrolled. There were no significant differences in proportion of complete tumor removal with free margins and re-excision rate; complete tumor removal with negative margins was seen in 87.7% of patients in the ROLL group versus 87.5% (p=0.97) of patients in the WGL group Re-excision was required in 11.7% of patients in the ROLL group versus 9.2% (p=0.47) in the WGL group. Incorrect preoperative localization (i.e. failure to identify the correct localization of the lesion) occurred in 5 (3%) patients in the ROLL group versus 0 patients in the WGL group (p=0.029). Differences in the volume of the excised specimen, duration of the procedure, success rate of the sentinel node procedure, surgeons’ preferences and patients’ pain perception are currently being analyzed. Conclusion: With this multicenter randomized controlled comparison, the first of its kind in patients with histologically proven breast cancer, we show that ROLL is not superior to WGL in terms of complete tumor excision and re-excision rates. Furthermore incorrect lesion localization occurred more frequently when applying ROLL. Data on long term (6 months) cosmetic results and quality of life (6 weeks, 3 months, 6 months) are awaited. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-01.

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r(-/-) mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r(-/-) mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.

The purpose of this study was to evaluate the mechanism by which Escherichia coli lipopolysaccharide stimulates the secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to those of terbutaline and TPA (protein kinase A and C activators respectively) and this effect was not suppressed by inhibitors of both protein kinases. On the other hand, lipopolysaccharide did not modify the increase on phosphatidylcholine secretion induced by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin, and enhanced slightly the calcium-ionophore A23187 stimulated phosphatidylcholine secretion. In addition, the stimulatory effect of lipopolysaccharide was suppressed by BAPTA, an intracellular Ca2+ chelator, and KN-62, a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results, together with the lipopolysaccharide-mediated increase in the cytosolic [Ca2+], suggest that stimulation of phosphatidylcholine secretion by lipopolysaccharide in type II pneumocytes occurs by a calcium-dependent transduction mechanism via Ca2+-calmodulin-dependent protein kinase activation.

Tumor necrosis factor α and interleukin-1β increase surfactant secretion in type II pneumocytes in a time- and dose-dependent manner. This stimulatory effect was additive to that of lipopolysaccharide, suggesting that cytokines and lipopolysaccharide may exert their actions through different signal transduction pathways. Tumor necrosis factor α and interleukin-1β did not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmaleimide (2 × 10-6M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (10-4M). In addition, the stimulatory effect of tumor necrosis factor α and interleukin-1β was not suppressed by the intracellular Ca2+ chelator BAPTA (5 × 10-6M) or by KN-62 (3 × 10-5M), a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results suggest that tumor necrosis factor α or interleukin-1β stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+ -independent manner.

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vi tamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition. (Mol Cell Biochem 175: 117–123, 1997)

BACKGROUND: Epidemiologic information on blood component usage can help improve the utilization of transfusion resources. STUDY DESIGN AND METHODS: Crosssectional survey in 2007 that included every hospital in Catalonia. Clinical data of blood recipients, including the four-digit International Classification of Diseases, 9th Revision, Clinical Modification codes and the indication for transfusion, were prospectively collected according to an established protocol. RESULTS: In total, 19,148 red blood cell (RBC) units, 1812 platelet (PLT) doses, and 3070 plasma units, transfused into 8019 patients (median age, 71 years; 52% males), were surveyed. Half the RBC units were used by patients older than 70 years. Specific diagnosis and procedures with the highest RBC use were lower limb orthopedic surgery (10.6% of all units) and gastrointestinal hemorrhage (6%). Therapeutic plasmapheresis (8.1%) and heart valve surgery (7.2%) were the procedures with the highest plasma use. Oncohematology patients accounted for 73% of transfused PLTs, more that two-thirds being administered for hemorrhage prophylaxis. Acute hemorrhage was the most common indication for RBC and plasma transfusion. Among all blood recipients, 80% received only RBCs and 6.9% received only plasma and/or PLTs, without concomitant RBCs. The population transfusion incidence rates were 35 RBC units, three PLT doses, and 6 plasma units per 1000 population-year. Demographic changes anticipate a 30% increase in RBC transfusion by year 2030. CONCLUSIONS: These results allow for identification of blood uses that are susceptible to improvement, help appraise the expected yield of blood safety measures, and will assist in planning the future blood supply.

The mechanisms involved in cellular activation and damage by bacterial endotoxins are not completely defined. In particular, there is little information about possible intracellular targets of endotoxins. Recently, the participation of a microtubule associated protein in endotoxin actions on macrophages has been suggested. In the present work, we have studied the effect of E. coli lipopolysaccharide on the polymerization of microtubular protein in vitro. Electrophoretic analysis of the polymerization mixtures showed that the endotoxin inhibited the polymerization when present at high concentrations. At lower concentrations, LPS selectively displaced the microtubule associated protein MAP-2 from the polymerized microtubules. Electron microscopy showed that LPS binds to microtubules of tubulin + MAPs and to microtubules of purified tubulin (without MAPs) polymerized with taxol. Gel filtration experiments confirmed the binding of LPS to tubulin, and by ligand blot assays an interaction LPS-MAP-2 was detected. The ability of LPS to interact with microtubular proteins suggests a possible participation of microtubules on the cellular effects of endotoxins.

A rat model of endotoxic shock was used to evaluate the effects of dimethylthiourea, a putative hydroxyl radical scavenger, in the alterations of lung phosphatidylcholine biosynthesis found during endotoxemia. Treatment of rats with dimethylthiourea, just before lipopolysaccharide injection, resulted in a decreased lipid peroxidation and an increase in phosphatidylcholine biosynthesis, although it did not prevent the body weight loss or the increase in lung weight and lung protein content associated with the lung injury induced by lipopolysaccharide. Our results suggest that phosphatidylcholine biosynthesis is impaired by processes in which hydroxyl radicals are implicated, although other oxygen free radical species, not removed by dimethylthiourea, can be also involved in lipopolysaccharide mediated lung injury.

Gran Torino and Doubt, two recent mainstream films, have the interplay of older adults and children as part of the dramatic story that unfolds in each film. There is a striking parallel in the them...

The purpose of this study is to evaluate the effect of the Escherichia coli lipopolysaccharide on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, in primary cultures of rat alveolar type II pneumocytes. Lipopolysaccharide stimulated phosphatidylcholine secretion in a time- and dose-dependent manner. At a concentration of 200 micrograms/ml, lipopolysaccharide stimulated the release of phosphatidylcholine 4-fold over the basal secretory rate, and the concentration producing half the maximal response was 20 micrograms/ml. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to that of the protein kinase C activator TPA, which is a potent stimulator of surfactant secretion. Lipopolysaccharide did not activate protein kinase C, which suggests that stimulation of phosphatidylcholine secretion by the endotoxin was through a mechanism independent of protein kinase C activation.

Alterations in pulmonary surfactant are partly responsible for the respiratory insufficiency seen under septic shock process. We have used an experimental model of LPS-induced shock in rats to examine the cells responsible for the pulmonary surfactant synthesis and its relationship to lung injury. (14C)Choline incorporation into phosphatidylcholine was significantly reduced in lung homogenates or type II cells obtained from LPS-treated animals. Addition of LPS in vitro fails to increase (14C)choline incorporation in type II cells obtained from LPS-treated animals. We suggest that this depression of pulmonary phosphatidylcholine synthesis may partly explain the occurrence of respiratory failure with septic shock.

The precise mechanisms involved in the endotoxin-induced shock are not yet clearly understood. A biphasic behaviour has been observed due to a direct interaction of bacterial lipopolysaccharide (LPS) with the membrane of target cells and an indirect activation of multiple homeostatic regulatory mechanisms (3).