Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study

Neuroendocrine tumor; Radionuclide therapyTumor neuroendocrí; Teràpia amb radionúclidsTumor neuroendocrino; Terapia con radionúclidosBackground Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). Results The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. Conclusion This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.The SEPTRALU registry received external funding from Novartis

Easy and inexpensive method for the visual and electronic detection of oxidants in air by using vinylic films with embedded aniline

Conventional nonconductive vinylic films with dispersed aniline change their color and become conductive in the presence of specific oxidant gases, namely, chlorine and hydrogen peroxide. The color change arises from the polymerization of the aniline to yield the conjugated polymer polyaniline, which at the same time renders the flexible vinylic films conductive. We present a simple and straightforward method using both colorimetric and electrical responses to detect and quantify the presence of oxidants (Cl2 and H2O2) in the air. Using RGB analysis (red, green and blue parameters defining the colors in digital pictures on a computer display) based on different pictures taken with a smartphone of discs extracted from the films and by measuring the UV–vis spectral variation in the presence of different concentrations of Cl2 and H2O2, we obtained limits of detection and quantification between 15 and 200 ppbv for H2O2 and between 37 and 583 ppbv for Cl2. Additionally, the electrical response was measured using a fabricated device to visually detect the electrical conductivity activation of the sensor in the presence of oxidant atmospheres, detecting a rapid decrease in resistivity (three orders of magnitude) when the polymerization of aniline began, changing the film from non-conductive to conductive.FEDER (Fondo Europeo de Desarrollo Regional) and the Spanish Agencia Estatal de Investigación (AEI) (MAT2017-84501-R

Porous aromatic polyamides the easy and green way

We prepared microporous aramid films through a simple, inexpensive and green way, using ionic liquids (IL) as porosity promoters. Commercial poly(m-phenylene isophthalamide) (MPIA) films with different IL proportions were prepared, and then microporous films were obtained by removing the IL in distilled water. Microporous films presented density values between 0.34 and 0.71 g⋅cm−3 (around five times lower to commercial MPIA), with a homogeneous and controlled cellular morphology dependent on the proportion of the IL, showing cell sizes in the microcellular range (radii between 1 and 8 µm). Thermal, mechanical and electrical properties (specifically ionic conductivity) of the aramid films were analyzed to evaluate the influence of the IL proportion. Finally, it was observed that the MPIA/IL system presented a reversible thermally induced phase-separation process around 60 °C, which was characterized through AFM-Raman images and spectra, together with the variation of the ionic conductivity.FEDER (Fondo Europeo de Desarrollo Regional) and both the Spanish Agencia Estatal de Investigación (MAT2017-84501-R) and the Consejería de Educación-Junta de Castilla y León (BU306P18

Effects of a pharmaceutical care program for patients with multiple sclerosis on immunomodulatory treatment adherence

Objetivos: Analizar el efecto de la implantación de un programa de atención farmacéutica específico para pacientes con esclerosis múltiple sobre la adherencia al tratamiento inmunomodulador. Conocer con que fármacos han sido tratados, su duración, los tipos de tratamiento de inicio así como la frecuencia y sus motivos de cambio.Material y métodos: Programa de atención farmacéutica con un diseño pre-post exposición, longitudinal, prospectivo del 1 de junio a 31 de diciembre de 2011 sobre pacientes con esclerosis múltiple, en tratamiento con algún fármaco inmunomodulador parenterales dispensados de forma ambulatoria. Retrospectivamente también se recogieron y analizaron variables relacionadas con los tratamientos inmunomoduladores recibidos y con la adherencia: % de adherencia = (dosis de fármaco dispensadas/ dosis necesarias) x 100. Se utilizó como nivel de significación una p<0,05 y un intervalo de confianza del 95%.Resultados: La adherencia previa (97,3%) fue inferior a la obtenida durante el periodo de estudio (98,4%): -1,12 (IC 95%= -3,39 – 1,14; p= 0,326). El tratamiento más frecuentemente administrado e iniciado fue el interferón-β. La duración mediana de los tratamientos fue de 39,5 meses (6,5 - 172). El principal motivo de cambio fue la respuesta subóptima.Conclusiones: La adherencia fue siempre muy elevada y superior durante la fase prospectiva, pero no de manera significativa. Se observó un predominio de las terapias con interferón-β probablemente debido a ser el primer fármaco inmunomodulador disponible. El principal motivo de cambio observado fue la respuesta subóptima. Debido a su efectividad a largo plazo, los tratamientos inmunomoduladores se han mantenido durante largos periodos de tiempo.Aim: Analyze the effect of the implementation of a pharmaceutical care program specific for patients with multiple sclerosis on immunomodulatory treatment adherence. To know the drugs with which the patients have been treated, the duration, the types of treatment initiation, the frequency of change and its reasons.Methods: A prospective, longitudinal study with a pre/post exposure design regarding the pharmaceutical care program implemented. All multiple sclerosis patients treated with immunomodulatory drugs from June 1 to December 31, 2011, were included. Also retrospectively were collected and analyzed variables related to immunomodulatory treatments received and adherence: % adherence = (dispensed drug dose / dose necessary) x 100. Was used as a significance level of p <0.05 and a confidence interval of 95%.Results: Prior adherence (97.3%) was lower than that obtained during the study period (98.4%): -1.12 (95% CI = -3.39 a 1.14, P = 0.326). The most common treatment administered and initiated was the interferon-β. The median duration of treatment was 39.5 months (6.5 - 172). The main reason of change was the suboptimal response.Conclusion: Adherence was always very high and higher during the prospective phase, but not significantly. There was a predominance of therapies with interferon- β, probably due it was the first immunomodulatory drug available. The main reason of change observed was the suboptimal response. Because of its long-term effectiveness, immunomodulatory therapies have been maintained for long periods

Efectos de un programa de Atención Farmacéutica para pacientes con esclerosis múltiple sobre la adherencia al tratamiento inmunomodulador

Objetivos: Analizar el efecto de la implantación de un programa de atención farmacéutica específico para pacientes con esclerosis múltiple sobre la adherencia al tratamiento inmunomodulador. Conocer con que fármacos han sido tratados, su duración, los tipos de tratamiento de inicio así como la frecuencia y sus motivos de cambio. Métodos: Programa de atención farmacéutica con un diseño pre-post exposición, longitudinal, prospectivo del 1 de junio a 31 de diciembre de 2011 sobre pacientes con esclerosis múltiple, en tratamiento con algún fármaco inmunomodulador parenterales dispensados de forma ambulatoria. Retrospectivamente también se recogieron y analizaron variables relacionadas con los tratamientos inmunomoduladores recibidos y con la adherencia: % de adherencia= (dosis de fármaco dispensadas/ dosis necesarias) x 100. Se utilizó como nivel de significación una p<0,05 y un intervalo de confianza del 95%. Resultados: La adherencia previa (97,3%) fue inferior a la obtenida durante el periodo de estudio (98,4%): -1,12 (IC 95%= -3,39 – 1,14; p= 0,326). El tratamiento más frecuentemente administrado e iniciado fue el interferón-β. La duración mediana de los tratamientos fue de 39,5 meses (6,5 - 172). El principal motivo de cambio fue la respuesta subóptima. Conclusiones: La adherencia fue siempre muy elevada y superior durante la fase prospectiva, pero no de manera significativa. Se observó un predominio de las terapias con interferón-β probablemente debido a ser el primer fármaco inmunomodulador disponible. El principal motivo de cambio observado fue la respuesta subóptima. Debido a su efectividad a largo plazo, los tratamientos inmunomoduladores se han mantenido durante largos periodos de tiempo.Aim: Analyze the effect of the implementation of a pharmaceutical care program specific for patients with multiple sclerosis on immunomodulatory treatment adherence. To know the drugs with which the patients have been treated, the duration, the types of treatment initiation, the frequency of change and its reasons. Methods: A prospective, longitudinal study with a pre/post exposure design regarding the pharmaceutical care program implemented. All multiple sclerosis patients treated with immunomodulatory drugs from June 1 to December 31, 2011, were included. Also retrospectively were collected and analyzed variables related to immunomodulatory treatments received and adherence: % adherence = (dispensed drug dose / dose necessary) x 100. Was used as a significance level of p <0.05 and a confidence interval of 95%. Results: Prior adherence (97.3%) was lower than that obtained during the study period (98.4%): -1.12 (95% CI = -3.39 a 1.14, P = 0.326). The most common treatment administered and initiated was the interferon-β. The median duration of treatment was 39.5 months (6.5 - 172). The main reason of change was the suboptimal response. Conclusions: Adherence was always very high and higher during the prospective phase, but not significantly. There was a predominance of therapies with interferon- β, probably due it was the first immunomodulatory drug available. The main reason of change observed was the suboptimal response. Because of its long-term effectiveness, immunomodulatory therapies have been maintained for long periods

Effects of a pharmaceutical care program for patients with multiple sclerosis on immunomodulatory treatment adherence

Objetivos: Analizar el efecto de la implantación de un programa de atención farmacéutica específico para pacientes con esclerosis múltiple sobre la adherencia al tratamiento inmunomodulador. Conocer con que fármacos han sido tratados, su duración, los tipos de tratamiento de inicio así como la frecuencia y sus motivos de cambio.Métodos: Programa de atención farmacéutica con un diseño pre-post exposición, longitudinal, prospectivo del 1 de junio a 31 de diciembre de 2011 sobre pacientes con esclerosis múltiple, en tratamiento con algún fármaco inmunomodulador parenterales dispensados de forma ambulatoria. Retrospectivamente también se recogieron y analizaron variables relacionadas con los tratamientos inmunomoduladores recibidos y con la adherencia: % de adherencia= (dosis de fármaco dispensadas/ dosis necesarias) x 100. Se utilizó como nivel de significación una p&lt;0,05 y un intervalo de confianza del 95%.Resultados: La adherencia previa (97,3%) fue inferior a la obtenida durante el periodo de estudio (98,4%): -1,12 (IC 95%= -3,39 – 1,14; p= 0,326). El tratamiento más frecuentemente administrado e iniciado fue el interferón-β. La duración mediana de los tratamientos fue de 39,5 meses (6,5 - 172). El principal motivo de cambio fue la respuesta subóptima.Conclusiones: La adherencia fue siempre muy elevada y superior durante la fase prospectiva, pero no de manera significativa. Se observó un predominio de las terapias con interferón-β probablemente debido a ser el primer fármaco inmunomodulador disponible. El principal motivo de cambio observado fue la respuesta subóptima. Debido a su efectividad a largo plazo, los tratamientos inmunomoduladores se han mantenido durante largos periodos de tiempo.Aim: Analyze the effect of the implementation of a pharmaceutical care program specific for patients with multiple sclerosis on immunomodulatory treatment adherence. To know the drugs with which the patients have been treated, the duration, the types of treatment initiation, the frequency of change and its reasons.Methods: A prospective, longitudinal study with a pre/post exposure design regarding the pharmaceutical care program implemented. All multiple sclerosis patients treated with immunomodulatory drugs from June 1 to December 31, 2011, were included. Also retrospectively were collected and analyzed variables related to immunomodulatory treatments received and adherence: % adherence = (dispensed drug dose / dose necessary) x 100. Was used as a significance level of p &lt;0.05 and a confidence interval of 95%.Results: Prior adherence (97.3%) was lower than that obtained during the study period (98.4%): -1.12 (95% CI = -3.39 a 1.14, P = 0.326). The most common treatment administered and initiated was the interferon-β. The median duration of treatment was 39.5 months (6.5 - 172). The main reason of change was the suboptimal response.Conclusions: Adherence was always very high and higher during the prospective phase, but not significantly. There was a predominance of therapies with interferon- β, probably due it was the first immunomodulatory drug available. The main reason of change observed was the suboptimal response. Because of its long-term effectiveness, immunomodulatory therapies have been maintained for long periods

Squalene loaded nanoparticles effectively protect hepatic AML12 cell lines against oxidative and endoplasmic reticulum stress in a TXNDC5-dependent way

This article belongs to the Special Issue Olive Oil Antioxidant.Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and high-performance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5.This research was supported by grants (CIBEROBN, CB06/03/1012, 1 January 2008) from CIBER Fisiopatología de la Obesidad y Nutrición as initiative of FEDER-ISCIII, Ministerio de Ciencia e Innovación-Fondo Europeo de Desarrollo Regional (PID2019-104915RB-I00, 1 June 2020) and Fondo Social Europeo-Gobierno de Aragón (B16_20R, 26 March 2020). S.H.B. was recipient of a joint fellowship from the Universities of Zaragoza and Pau and J.S.-M. was recipient of a Fundación Cuenca Villoro fellowship.Peer reviewe