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Supplementary Figure Legends. Supplementary Figure 1: Targeted disruption of AMPKα1/2 does not affect arsenicinducible phosphorylation of AKT at Ser473. Supplementary Figure 2: As- Biotin binds to AMPKα as measured by mass spectroscopy

Soil-transmitted helminths, such as

Background and Aims Management of inflammatory bowel disease [IBD] is complex and IBD Comprehensive Care Units [ICCUs] facilitate the delivery of quality care to IBD patients. The objective of this study was to update the existing set of quality indicators [QIs] for ICCUs, based on a nationwide quality certification programme carried out in Spain, from a multi-stakeholder perspective and using multicriteria decision analysis [MCDA] methodology. Methods An MCDA comprising three different phases was conducted. In phase 1, a systematic literature review was performed, and after validation by a scientific committee comprising 11 experts, a preliminary set of QIs was developed. In phase 2, a larger group of 49 experts determined the relevance and relative importance of each QI by prioritising and weighing the preliminary set. Finally in phase 3, the scientific committee reviewed the results and made a final selection via a deliberative process. Results The final set comprised 67 QIs, classified as Structure [23 QIs], Process [35 QIs] and Outcome [9 QIs], which were ranked according to their relative importance. Multidisciplinary management was the most important requirement in ICCUs, followed by continuity of care, standardisation of clinical care and, especially, the incorporation of patients’ reported outcomes. Conclusions This updated set of QIs comprises a weighted and prioritised set of items that represent the essential minimum of criteria for ensuring appropriate quality of care in the management of IBD patients.

Introducción: Diferentes vacunas frente a SARS-CoV-2 están actualmente en el mercado y se recomiendan en pacientes con Enfermedad Inflamatoria Intestinal (EII). No tenemos suficiente evidencia sobre la aceptación de este tipo de vacunas. El objetivo del estudio fue evaluar la aceptación de la vacuna frente a SARS-CoV-2 por parte de gastroenterólogos y pacientes con EII. Métodos: Se realizó una encuesta online a 8000 pacientes de ACCU-España y 1000 miembros de GETECCU. Se enviaron tres invitaciones entre Octubre-Diciembre 2020. Se realizó un análisis descriptivo, comparando las respuestas de médicos y pacientes. Resultados: 144 gastroenterólogos [63% mujeres, edad media 43 años (DE 9,5)], y1302 pacientes [72% mujeres, edad media 43 años (DE 12)] respondieron a la encuesta. 95% de los médicos recomendaban la vacuna frente a SARS-CoV-2 en pacientes con EII, 87% consideraron que su estrategia de vacunación frente a diferentes vacunas no había cambiado tras la pandemia frente al 12% que consideraban que actualmente remitían más pacientes a vacunación. En cuanto a los pacientes con EII, sólo 43% aceptaban la vacunación frente a SARS-CoV-2, frente a 43% que no estaban seguros. El sexo masculino (p

Background Using effective antiretroviral therapy to consistently suppress plasma HIV RNA levels to < 200 copies/mL is known to improve morbidity and mortality at all stages of HIV infection and prevent transmission to sexual partners. Logistical challenges such as transporting, processing, and storing samples may threaten the accuracy of the test results. Plasma Preparation tubes (PPT) or Ethylene Diamine Tetra Acetic Acid (EDTA) tubes can be used for this test. PPT tubes contain an inert gel that migrates during centrifugation, forming a barrier between the plasma and cellular elements. Adequate separation of cellular elements may not always occur, and this can result in falsely elevated HIV Viral load (VL) due to measurement of integrated intracellular virus. It is therefore routine practice to centrifuge samples twice when PPT tubes are used. This is not necessary with EDTA tubes. In addition, there are reports that HIV RNA levels may be higher with PPT tubes are used, compared to EDTA tubes. Methods This is a quality improvement project that reviews a series of falsely elevated HIV VL in a group of patients who reported adherence and had been previously virologically suppressed. Results A total of 20 unexpectedly elevated HIV VL were identified from January to March of 2020 after introduction of a new phlebotomist in our clinic. VL ranged from 200-2530 copies/ml. Most patients (18/20) had history of virologic suppression and reported adherence. We standardized our process by using only PPT tubes and centrifuging samples twice prior to processing. Our nurses reported visible residual cellular elements in some of the plasma specimens in the tubes even after appropriate centrifugation. We continued to see suspected erroneous results. We repeated the test in EDTA tubes. 16/19 had HIV VL < 20, the remainder ranged from 27-41 copies/ml. We then implemented the use of EDTA tubes in all samples. No further cases of falsely elevated VL have been seen since the change. Table 1 Conclusion We describe potential steps that can interfere in the accuracy of HIV VL results. Detailed review of past history and patient’s adherence to treatment is essential to identify systemic problems that may lead to errors. Close communication with staff and laboratory provider will be key to overcome such challenges. Disclosures All Authors: No reported disclosures

Background Hepatotoxicity secondary to therapy for Mycobacterium tuberculosis (MTB) is a common complication that may lead to treatment interruption. N-Acetylcysteine (NAC) exerts a hepatoprotective effect by repleting glutathione stores and enhancing the cellular antioxidant defense mechanism. NAC has been found to be protective against liver toxicity in animals treated for MTB infection. Randomized controlled trials have shown that its use in humans also decreases the risk of hepatotoxicity associated with anti-MTB treatment but there is minimal data regarding its utility for treatment of liver toxicity. Methods Patients who received NAC from January 2012 to March 2018 for prophylaxis and treatment of increasing liver function tests (LFTs) while on isoniazid (INH) were included. A retrospective review of the medical record system was performed. Results Nineteen patients were included. Eight received NAC for treatment. The average age was 49 years. Seventy percent of patients were male. The mean BMI was 25. Five patients had underlying liver cirrhosis and two had hepatic steatosis. Eleven patients had Hepatitis C (HCV) and one had active Hepatitis B infection. Ten patients had MTB pulmonary infection, thee had latent TB infection, two meningitis, and three had disseminated disease. One patient was treated for atypical mycobacterial infection. The dose of NAC used was 600 mg oral twice daily and the duration was variable. The prophylaxis group had stable LFTs during treatment, except for two patients whose enzymes increased more than three times the upper limit of normal. These two patients had underlying HCV and liver cirrhosis. Only one required discontinuation of INH. This group received NAC for an average of 47 days. The treatment group had a favorable trend of liver enzymes after NAC initiation, with levels significantly improving by day 14 (Figures 1 and 2). Three patients did not require discontinuation of antibiotics. INH was stopped prior to NAC initiation in four patients. No side effects of NAC were documented in any patient. Conclusion NAC is a safe and effective measure to prevent and treat hepatotoxicity secondary to INH therapy. More studies are needed to determine its optimal dose and duration for this indication. Disclosures All authors: No reported disclosures.

While a good hydration state is essential for health maintenance, the dehydration state, produced by the imbalance between fluid intake and fluid losses, could be related to an inflammatory situati...

Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. We provide evidence that arsenic can directly bind to cysteine 299 in AMPKα and inhibit its activity. This inhibition of AMPK by arsenic is required in part for its cytotoxic effects on primitive leukemic progenitors from patients with AML, while concomitant treatment with an AMPK activator antagonizes in vivo the arsenic-induced antileukemic effects in a xenograft AML mouse model. A consequence of AMPK inhibition is activation of the mTOR pathway as a negative regulatory feedback loop. However, when AMPK expression is lost, arsenic-dependent activation of the kinase RSK downstream of MAPK activity compensates the generation of regulatory feedback signals through phosphorylation of downstream mTOR targets. Thus, therapeutic regimens with As2O3 will need to include inhibitors of both the mTOR and RSK pathways in combination to prevent engagement of negative feedback loops and maximize antineoplastic responses. Mol Cancer Ther; 14(1); 202–12. ©2014 AACR.

Disease-Related Malnutrition (DRM) is present in a high percentage of patients admitted to hospital and their impact is diverse and of great importance.Nutrition Department of University Hospital La Paz, in collaboration with all members of the Nutrition Committee, we decided to implement some method of screening in our centre which allowed us to detect as many patients with malnutrition risk as possible.Due to the large size of our centre, with about 1,500 beds and the few human resources in our unit, we chose to use the CONUT system (Nutritional Control), a 100% automatic method based on analytical parameters, very easy to use, low cost and whose validity is confirmed, characteristics that fulfilled our needs. The method collects information from databases of Admission Service (affiliation, age, date) and Laboratory (albumin, cholesterol, total lymphocytes) and generates, in the report of analytical results, "alert" information about each patient''s nutritional risk and also nutritional recommendations based on the risk identified. Prior to its implantation several evaluations were performed in order to allow us to better know the extra workload, as it was the main factor that could limit our ability to assume that screening method and also many training activities for doctors and hospital health professionals who were increasingly assuming responsibilities in the nutritional treatment of their patients. This screening system has been working from June of 2010 and it has detected risk of malnutrition in 32% of the evaluated patients. In general, only in those cases where the alert corresponded to a high-risk nutritional situation, which represents approximately 10% of the total, specialized intervention by the Clinical Nutrition Unit was required. Later, as we have detected some possible causes that justify the system does not work properly; the screening system has undergone several changes . In this sense, we have made a retrospective evaluation of 233 patients admitted to the General Surgery plants and documented that those entering for scheduled surgery, having a alarm of malnutrition (50% of cases), its presence increases significantly the hospital stay and mortality.The implementation of this nutritional screening method has led to a change in the "nutritional" culture of our centre respect to DRM in most of our professionals: doctors and nurses and even in the management team, so all of them understand the importance of the process and know about the available tools and knowledge to indicate an adequate and early nutritional support.La malnutrición asociada a la enfermedad (MAE) está presente en un porcentaje muy elevado de los pacientes que ingresan en los hospitales y su repercusión es diversa y de mucha trascendencia. Objetivo. Desde la Unidad de Nutrición del Hospital Universitario la Paz, en colaboración con todos los miembros de la Comisión de Nutrición, nos planteamos implantar algún método de cribado en nuestro centro, que permitiese abarcar al mayor número posible de pacientes. Resultados. Debido al gran tamaño de nuestro centro, con cerca de 1500 camas, unido a una escasez de recursos humanos en nuestra unidad, optamos por utilizar el sistema de cribado CONUT (Control Nutricional) 100 % automático y basado en parámetros analíticos, muy fácil de manejar, de bajo coste y cuya validez está confirmada, adaptándolo a nuestras necesidades. El método recoge información de las bases de datos del servicio de Admisión (filiación, edad, fecha) y del Laboratorio (albúmina, colesterol, linfocitos totales) y genera, en el informe de resultados de los análisis clínicos, la información sobre la alerta de riesgo nutricional de cada paciente, así como las recomendaciones nutricionales a seguir en función del riesgo detectado en cada caso. Para llegar su implantación se llevaron a cabo diferentes evaluaciones que nos permitieron conocer previamente la carga extra de trabajo que podría generar su implantación y nuestra capacidad para asumirlas, así como numerosas actividades formativas encaminadas a que los médicos y profesionales sanitarios del hospital asumieran cada vez más responsabilidades en el proceso del tratamiento nutricional de sus pacientes. Este sistema de cribado funciona desde Junio del año 2010 y detecta riesgo de desnutrición en el 32 % de los pacientes evaluados. En general, sólo en los casos en los que la alerta corresponde a una situación de Alto riesgo nutricional, hecho que se da aproximadamente en el 10 % del total, se requirió la intervención especializada por parte de la Unidad de Nutrición Clínica y Dietética. Posteriormente, conforme hemos ido detectando posibles causas que justificaran que el sistema no funcionase adecuadamente, el sistema de cribado ha sido objeto de diversas modificaciones. En este sentido, se ha realizado una evaluación retrospectiva en 233 pacientes ingresados en las plantas de Cirugía General y se ha documentado que aquellos que ingresan para cirugía programada y presentan una alarma alta o moderada de desnutrición (el 50 % de los casos), la presencia de la misma aumenta significativamente los días de ingreso y la mortalidad. Conclusiones. La implantación del cribado nutricional ha favorecido un cambio en la cultura de nuestro centro con respecto a la malnutrición asociada a la enfermedad y la mayoría de nuestros profesionales, tanto médicos como enfermeras e incluso el equipo directivo, comprenden la importancia del proceso y saben que disponemos de herramientas y de conocimiento suficiente para indicar un soporte nutricional adecuado y precoz.

Arsenic compounds exert important biological effects and arsenic trioxide has been approved by the Food and Drug Administration (FDA) for the treatment of patients with acute promyelocytic leukemia (APL). Much of arsenic’s actions in cells reflect its ability to bind thiol groups in cellular proteins or to affect the production of reactive oxygen species (ROS), leading to the engagement and regulation of several cellular signaling pathways. Arsenic has been also shown to degrade abnormal fusion proteins found in myeloid leukemias. It has also been shown to effect NFκB, MAPK, mTOR and Hedgehog pathways which can modulate the viability of cancer cells. Many clinical trials have been performed to examine the clinical efficacy of arsenic trioxide alone or in combination with other agents in the treatment of various hematological malignancies. The continuous advances in basic and translational research and the better understanding of the mechanisms of action of arsenic should lead to more effective combinations with other agents that could result in better clinical outcomes.