Sequential versus Standard Triple Therapy for First-Line Helicobacter pylori Eradication: An Update.

BACKGROUND: non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-Helicobacter pylori treatment alternative to standard triple therapy (STT). METHODS: We conducted a systematic review with a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of 10-day SEQ vs. STT (of at least 7 days) using bibliographical searches up to July 2021, including treatment-naïve adult or children. The intention-to-treat (ITT) eradication rate and the risk difference (RD) were calculated. RESULTS: Overall, 69 RCTs were evaluated, including 19,657 patients (9486 in SEQ; 10,171 in STT). Overall, SEQ was significantly more effective than STT (82% vs. 75%; RD 0.08; p < 0.001). The results were highly heterogeneous (I2 = 68%), and 38 studies did not demonstrate differences between therapies. Subgroup analyses suggested that patients with clarithromycin resistance only and all geographical areas but South America could benefit more from SEQ. Both therapies have evolved over the years, showing similar results when STT lasted 14 days; however, a tendency toward lower SEQ efficacy was noted from 2010 onwards. CONCLUSIONS: Prior to 2010, SEQ was significantly more effective than STT, notably when 7-day STT was prescribed. A tendency toward lower differences between SEQ and STT has been noted, especially when using 10-day STT. None of the therapies achieved an optimal efficacy and therefore cannot be recommended as a valid first-line H. pylori treatment.

Oribatid mites in different Mediterranean crop rotations fertilized with animal droppings.

Unsustainable soil management is one of the drivers of soil degradation, but impact assessment requires the development of indicators. Oribatids might be considered as early indicators of disturbances due to the stability of their community. The aim of this study was to investigate the feasibility of oribatids as bioindicators of sustainable agricultural practices. Under a dry Mediterranean climate, three fertilization experiments - two under a two-crop rotation system and one under maize monoculture and established 12 years earlier - were sampled 3× for oribatid identification during the last annual cropping cycle. The hypothesis was that different nutrient and crop managements affect the number of oribatid species and individuals present, and these parameters could be used as indicators of soil degradation. In total, 18 oribatid species were identified, and 1974 adult individuals were recovered. Maximum abundance was found prior to sowing. Pig slurry (PS) vs. control, and dairy cattle manure (CM) vs. mineral fertilization increased oribatid abundance. This increase was evident when the average applied rates with PS were ca. 2 Mg of organic matter (OM) ha- 1 yr- 1, or higher than ca. 4 Mg OM ha- 1 yr- 1 for CM. When the preceding crop was wheat and PS or CM were used, Oribatula (Zygoribatula) excavata (which reproduces sexually) predominated. In maize monoculture fertilized with CM, Tectocepheus sarekensis and Acrotritia ardua americana (which can reproduce through parthenogenesis) prevailed vs. Oribatula, which indicated a heavily disturbed soil. Under this specific Mediterranean environment, the predominance of certain parthenogenic oribatid species and the number of individuals provide advanced warning on soil degradation.

Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies.

Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes. Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed. Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control. Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy.

All-trans retinoic acid works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T cells.

B-cell maturation antigen (BCMA) is the lead antigen for chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM). A challenge is inter- and intra-patient heterogeneity in BCMA expression on MM cells and BCMA downmodulation under therapeutic pressure. Accordingly, there is a desire to augment and sustain BCMA expression on MM cells in patients that receive BCMA-CAR T-cell therapy. We used all-trans retinoic acid (ATRA) to augment BCMA expression on MM cells and to increase the efficacy of BCMA-CAR T cells in pre-clinical models. We show that ATRA treatment leads to an increase in BCMA transcripts by quantitative reverse transcription polymerase chain reaction and an increase in BCMA protein expression by flow cytometry in MM cell lines and primary MM cells. Analyses with super-resolution microscopy confirmed increased BCMA protein expression and revealed an even distribution of non-clustered BCMA molecules on the MM cell membrane after ATRA treatment. The enhanced BCMA expression on MM cells after ATRA treatment led to enhanced cytolysis, cytokine secretion and proliferation of BCMA-CAR T cells in vitro, and increased efficacy of BCMA-CAR T-cell therapy in a murine xenograft model of MM in vivo (NSG/MM.1S). Combination treatment of MM cells with ATRA and the γ- secretase inhibitor crenigacestat further enhanced BCMA expression and the efficacy of BCMA-CAR T-cell therapy in vitro and in vivo. Taken together, the data show that ATRA treatment leads to enhanced BCMA expression on MM cells and consecutively, enhanced reactivity of BCMA-CAR T cells. The data support the clinical evaluation of ATRA in combination with BCMA-CAR T-cell therapy and potentially, other BCMA-directed immunotherapies.

Recomendaciones para profesionales no anestesiólogos en procedimientos de sedoanalgesia / Recommendations for non-anaesthesia providers in sedation and analgesia procedures

El dolor, y la ansiedad que este produce, son las primeras causas de sufrimiento en los niños que acuden a los servicios de urgencias, motivando un aumento del interés de padres y sanitarios para proporcionar una adecuada analgesia y sedación.Por ello, en los últimos años se ha producido un incremento en el número de procedimientos diagnósticos y terapéuticos en niños que requieren sedoanalgesia en urgencias pediátricas, lo que ha originado una necesidad de formación de personal no anestesiólogo para cubrir ese requisito sin afectar a la seguridad del paciente.El objetivo de este documento de consenso es establecer recomendaciones basadas en la evidencia científica, elaboradas y consensuadas por el Grupo de Trabajo de Sedoanalgesia de la Sociedad Española de Urgencias de Pediatría, sobre las competencias y la capacitación del personal que realiza procedimientos de sedoanalgesia para conseguir un óptimo manejo del paciente pediátrico antes, durante y después del procedimiento en los servicios de urgencias pediátricas.El documento de consenso se ha estructurado en dos partes: la primera hace referencia a las competencias del personal no anestesiólogo que realiza procedimientos de sedoanalgesia, y la segunda, a la forma de obtener la capacitación necesaria. Se ha elaborado un listado de preguntas de investigación, se han definido unas palabras clave y se ha realizado una búsqueda bibliográfica desglosando la evidencia disponible. Los resultados se muestran como conclusiones, sometidas a votación anónima por cada uno de los miembros del Grupo de Trabajo. En cada conclusión se indica el porcentaje obtenido en la votación. (AU)

Pain and the anxiety that it produces are the main sources of suffering in children managed in emergency departments, eliciting a growing interest in parents and health care providers in the adequate provision of sedation and analgesia.In consequence, the number of diagnostic and therapeutic procedures that require sedation and/or analgesia in paediatric emergency departments has increased in recent years, which has generated a need to train non-anaesthesiologists on how to provide this care without affecting patient safety.The objective of this document is to establish evidence-based recommendations, developed by consensus by the Working Group on Sedation and Analgesia of the Sociedad Española de Urgencias de Pediatría, regarding the competencies and training of staff who perform sedation or analgesia procedures to achieve the greatest possible quality in the management of paediatric patients before, during and after these procedures in the paediatric emergency care setting.The consensus document has been structured in two parts: the first addresses the competencies of non-anaesthesiologists who perform sedoanalgesia procedures, and the second how to obtain the necessary training. A list of research questions was prepared, keywords defined and a literature search carried out to break down and summarise the available evidence. The results are presented in the form of conclusions, which were subjected to anonymous voting by each of the members of the working group. For each of the conclusions, we provide the percent agreement obtained in the voting. (AU)

Recommendations for non-anaesthesia providers in sedation and analgesia procedures.

Pain and the anxiety that it produces are the main sources of suffering in children managed in emergency departments, eliciting a growing interest in parents and health care providers in the adequate provision of sedation and analgesia. In consequence, the number of diagnostic and therapeutic procedures that require sedation and/or analgesia in paediatric emergency departments has increased in recent years, which has generated a need to train non-anaesthesiologists on how to provide this care without affecting patient safety. The objective of this document is to establish evidence-based recommendations, developed by consensus by the Working Group on Sedation and Analgesia of the Sociedad Española de Urgencias de Pediatría, regarding the competencies and training of staff who perform sedation or analgesia procedures to achieve the greatest possible quality in the management of paediatric patients before, during and after these procedures in the paediatric emergency care setting. The consensus document has been structured in two parts: the first addresses the competencies of non-anaesthesiologists who perform sedoanalgesia procedures, and the second how to obtain the necessary training. A list of research questions was prepared, keywords defined and a literature search carried out to break down and summarise the available evidence. The results are presented in the form of conclusions, which were subjected to anonymous voting by each of the members of the working group. For each of the conclusions, we provide the percent agreement obtained in the voting.

Multicenter study of lumen-apposing metal stents with or without pigtail in endoscopic ultrasound-guided biliary drainage for malignant obstruction-BAMPI TRIAL: an open-label, randomized controlled trial protocol.

BACKGROUND: It is unclear whether the insertion of an axis-orienting double-pigtail plastic stent (DPS) through biliary lumen-apposing meal stent (LAMS) in EUS-guided choledochoduodenostomy (CDS) improves the stent patency. The aim of this study is to determine whether this technical variant offers a clinical benefit in EUS-guided biliary drainage (BD) for the management of distal malignant biliary obstruction. METHODS/DESIGN: This is a multicenter open-label, randomized controlled trial with two parallel groups. Eighty-four patients with malignant biliary obstruction will undergo EUS-BD (CDS type) using LAMS in 7 tertiary hospitals in Spain and will be randomized to the LAMS and LAMS plus DPS groups. The primary endpoint is the rate of recurrent biliary obstruction, as a stent dysfunction parameter, detected during follow-up. Secondary endpoints: technical and clinical success (reduction in bilirubin > 50% within 14 days of stent placement), safety, and others (number of reinterventions, time to biliary obstruction, prognostic factors, survival rate). DISCUSSION: The BAMPI trial has been designed to determine whether the addition of a coaxial axis-orienting DPS through LAMS is superior to LAMS alone to prevent stent dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT04595058 . Registered on October 14, 2020.

Manejo de la infección por Helicobacter pylori en la edad pediátrica / Management of Helicobacter pylori infection in the pediatric age

El manejo de la infección por Helicobacter pylori en los niños es un dilema permanente en la práctica clínica. A lo largo de los años se han ido creando multitud de interrogantes respecto a los síntomas ligados a la infección, los métodos diagnósticos y los modos de tratamiento, siendo la más controvertida la indicación diagnóstica.En los últimos 10 años el colectivo pediátrico ha dispuesto de una guía elaborada por expertos de las Sociedades de Gastroenterología Pediátrica de Europa (ESPGHAN) y Estados Unidos (NASPGHAN) publicada en 2011 y actualizada en 2017 que nos ha orientado en el manejo de la infección por H.pylori en la edad pediátrica.El presente documento pretende unificar los criterios de indicación de estudio así como las pautas de diagnóstico y tratamiento de la infección por H.pylori en los niños y adolescentes para que puedan ser utilizadas tanto en atención primaria como en la clínica hospitalaria. (AU)

The management of Helicobacter pylori infection in children is a consistent problem in clinical practice. Over the years, many questions have been raised regarding symptoms associated with the infection, the diagnostic methods and type of treatment. What is most controversial is determining the criteria that enable us to initiate and carry out the study in children.In the last 10 years, pediatricians have followed the joint ESPGHAN/NASPGHAN guidelines published in 2011 and updated in 2017 in the management of H.pylori in children.This document aims to unify the study indication criteria as well as the diagnosis and treatment recommendations for H.pylori infection in children and adolescents, so they can be used in both Primary and Hospital care. (AU)

Management of Helicobacter pylori infection in the pediatric age.

The management of Helicobacter pylori infection in children is a consistent problem in clinical practice. Over the years, many questions have been raised regarding symptoms associated with the infection, the diagnostic methods and type of treatment. What is most controversial is determining the criteria that enable us to initiate and carry out the study in children. In the last 10 years, pediatricians have followed the joint ESPGHAN/NASPGHAN guidelines published in 2011 and updated in 2017 in the management of H. pylori in children. This document aims to unify the study indication criteria as well as the diagnosis and treatment recommendations for H. pylori infection in children and adolescents, so they can be used in both Primary and Hospital care.

[Management of Helicobacter pylori infection in the pediatric age]. / Manejo de la infección por Helicobacter pylori en la edad pediátrica.

The management of Helicobacter pylori infection in children is a consistent problem in clinical practice. Over the years, many questions have been raised regarding symptoms associated with the infection, the diagnostic methods and type of treatment. What is most controversial is determining the criteria that enable us to initiate and carry out the study in children. In the last 10 years, pediatricians have followed the joint ESPGHAN/NASPGHAN guidelines published in 2011 and updated in 2017 in the management of H.pylori in children. This document aims to unify the study indication criteria as well as the diagnosis and treatment recommendations for H.pylori infection in children and adolescents, so they can be used in both Primary and Hospital care.

Valoración del documento: "Recomendaciones generales relacionadas con las decisiones éticas difíciles y la adecuación de la intensidad asistencial/ingreso en las Unidades de Cuidados Intensivos en situaciones excepcionales de crisis" por parte del Consejo Asesor Regional de Ética Asistencial –Dr. D. Juan Gómez Rubí– (carea) / Evaluation of the document: "General recommendations related to difficult ethical decisions and the adequacy of the health care/admission in the Intensive Care Units in exceptional crisis situations" by the Regional Advisory Council of Health Care Ethics. –D. Juan Gómez Rubí- (carea)

No disponible

Bio-Based Packaging: Materials, Modifications, Industrial Applications and Sustainability.

Environmental impacts and consumer concerns have necessitated the study of bio-based materials as alternatives to petrochemicals for packaging applications. The purpose of this review is to summarize synthetic and non-synthetic materials feasible for packaging and textile applications, routes of upscaling, (industrial) applications, evaluation of sustainability, and end-of-life options. The outlined bio-based materials include polylactic acid, polyethylene furanoate, polybutylene succinate, and non-synthetically produced polymers such as polyhydrodyalkanoate, cellulose, starch, proteins, lipids, and waxes. Further emphasis is placed on modification techniques (coating and surface modification), biocomposites, multilayers, and additives used to adjust properties especially for barriers to gas and moisture and to tune their biodegradability. Overall, this review provides a holistic view of bio-based packaging material including processing, and an evaluation of the sustainability of and options for recycling. Thus, this review contributes to increasing the knowledge of available sustainable bio-based packaging material and enhancing the transfer of scientific results into applications.

Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma.

Multiple myeloma (MM) remains an incurable disease regardless of recent advances in the field. Therefore, a substantial unmet need exists to treat patients with relapsed/refractory myeloma. The use of novel agents such as daratumumab, elotuzumab, carfilzomib, or pomalidomide, among others, usually cannot completely eradicate myeloma cells. Although these new drugs have had a significant impact on the prognosis of MM patients, the vast majority ultimately become refractory or can no longer be treated due to toxicity of prior treatment, and thus succumb to the disease. Cellular therapies represent a novel approach with a unique mechanism of action against myeloma with the potential to defeat drug resistance and achieve long-term remissions. Genetic modification of cells to express a novel receptor with tumor antigen specificity is currently being explored in myeloma. Chimeric antigen receptor gene-modified T-cells (CAR T-cells) have shown to be the most promising approach so far. CAR T-cells have shown to induce durable complete remissions in other advanced hematologic malignancies like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). With this background, significant efforts are underway to develop CAR-based therapies for MM. Currently, several antigen targets, including CD138, CD19, immunoglobulin kappa (Ig-Kappa) and B-cell maturation antigen (BCMA), are being used in clinical trials to treat myeloma patients. Some of these trials have shown promising results, especially in terms of response rates. However, the absence of a plateau is observed in most studies which correlates with the absence of durable remissions. Therefore, several potential limitations such as lack of effectiveness, off-tumor toxicities, and antigen loss or interference with soluble proteins could hamper the efficacy of CAR T-cells in myeloma. In this review, we will focus on clinical outcomes reported with CAR T-cells in myeloma, as well as on CAR T-cell limitations and how to overcome them with next generation of CAR T-cells.

Oropharyngeal Colostrum Positively Modulates the Inflammatory Response in Preterm Neonates.

During the first days of life, premature infants have physiological difficulties swallowing, thereby missing out on the benefits of breastfeeding. The aim of this study is to assess the effects of oropharyngeal mother's milk administration in the inflammatory signaling of extremely premature infants. Neonates (n = 100) (<32 week's gestation and/or <1500 g) were divided into two groups: mother's milk group (n = 48), receiving 0.2 mL of oropharyngeal mother's milk every 4 h for the first 15 days of life, and a control group (n = 52), not receiving oropharyngeal mother's milk. Serum concentrations of interleukin (IL) IL-6, IL-8, IL-10, IL-1ra, tumor necrosis factor alpha (TNF-α), and interferón gamma (IFN-γ) were assessed at 1, 3, 15, and 30 days of postnatal life. Maternal and neonatal outcomes were collected. The rate of common neonatal morbidities in both groups was similar. The mother's milk group achieved full enteral feeding earlier, and showed a decrease in Il-6 on days 15 and 30, in IL-8 on day 30, and in TNF-α and INF-γ on day 15, as well as an increase in IL-1ra on days 3 and 15 and in IL-10 on day 30. Oropharyngeal mother's milk administration for 15 days decreases the pro-inflammatory state of preterm neonates and provides full enteral nutrition earlier, which could have a positive influence on the development of the immune system and inflammatory response, thereby positively influencing other developmental outcomes.

International multicenter comprehensive analysis of adverse events associated with lumen-apposing metal stent placement for pancreatic fluid collection drainage.

BACKGROUND AND AIMS: High rates of technical and clinical success were reported for lumen-apposing metal stent (LAMS) placement for peripancreatic fluid collection (PFC) drainage. However, data on the adverse event (AE) rates are heterogeneous. The aim of this study was to evaluate the incidence, severity, management, and risk factors of AEs related to the use of LAMSs for drainage of PFCs in a large cohort of patients. METHODS: This is a multicenter, international, retrospective review from 15 centers of all patients who underwent placement of LAMSs for the management of PFCs. A nested case-control study was conducted in patients with (case) or without (control) AEs. RESULTS: Three hundred thirty-three procedures in 328 patients were performed (5 patients treated with 2 LAMSs). Technical success was achieved in 321 patients (97.9%). Three hundred four patients were finally included in the study (7 excluded for lost to follow-up information; 10 excluded for deaths unrelated to LAMSs). The rate of clinical success was 89.5%. Seventy-nine LAMS-related AEs occurred in 74 of 304 patients (24.3%), after a mean time of 25.3 days (median, 18 days; interquartile range, 6-30) classified as 20 (25.3%) mild, 54 (68.4%) moderate, or 5 (6.3%) severe. On multivariable analysis compared with control subjects, cases were more likely to have walled-off necrosis (WON) versus pancreatic pseudocysts (odds ratio, 2.18; 95% confidence interval, 1.09-4.46; P = .028), whereas cases were less likely to have undergone tract (balloon) dilation (yes vs no; odds ratio, .47; 95% confidence interval, .22-.93; P = .034). CONCLUSIONS: Data from this large international retrospective study confirm that the use of LAMSs for management of PFCs has excellent technical and good clinical success rates. The rate of AEs, however, is not negligible and should be carefully considered before using these stents for drainage of PFCs and in particular for WON. Further prospective studies are needed to confirm these findings. (Clinical trial registration number: NCT03544008.).

Bienestar de la mujer durante el proceso de parto: comparación de dos herramientas de evaluación / Women's welfare during the process of childbirth: a comparison of two evaluation tolos

OBJETIVO: Describir la experiencia y el bienestar de las mujeres durante el proceso de parto atendido en el Área de Salud 2-Cartagena, del Servicio Murciano de Salud, y relacionarlos con las características ociodemográficas y obstétricas de la muestra y discutir la adecuación de las escalas utilizadas CEQ-E y BMSP2 en el entorno donde se emplean. MÉTODO: Estudio descriptivo de corte transversal realizado sobre 120 mujeres con parto eutócico. Los datos fueron recogidos mediante las encuestas CEQ-E y BMSP2. RESULTADOS: El bienestar y la experiencia durante el parto fueron valorados entre adecuados y óptimos por un 83,8% de las participantes (120 mujeres) con la escala BMSP2, y con una puntuación media de 3,19 sobre 4 puntos con la herramienta CEQ-E. Los resultados de las subescalas indican que el apoyo profesional y el contacto madre-hijo fueron las dimensiones mejor valoradas. El bienestar y la satisfacción no se relacionaron con la edad, la fórmula obstétrica, el tipo de inicio de parto, la duración del parto y el desgarro durante el expulsivo. Únicamente la nacionalidad y el tipo de anestesia se relacionaron de forma estadísticamente significativa con algunas de las subescalas de las herramientas utilizadas. Entre las dos escalas de nuestro estudio existe una correlación positiva moderada (R = 0,557) que contribuye a la validez de criterio de la escala BMSP2. CONCLUSIONES: La correlación positiva entre las dos herramientas nos indica que ambas pueden ser útiles en contextos culturales como el mediterráneo, en el que son valoradas tanto la autoeficacia (dimensión que enfatiza la herramienta CEQ-E elaborada en Suecia) como la participación de la familia (dimensión incluida en la herramienta chilena BMSP2)

OBJECTIVE: Describe the experience and well-being of women in Area II of the Murcian Health Service during the birth process, and relate them to the sociodemographic and obstetric characteristics of the sam-ple, and discuss the adequacy of the scales used CEQ-E and BMSP2 in the environment where they are used. METHOD: Descriptive crosssectional study performed on 120 women with eutocic delivery. The data was collected through the CEQ-E and BMSP2 surveys. RESULTS: The level of well-being was assessed as adequate and optimal in 83.8% of the participants (120 women), with the BMSP2 scale, and with an average score of 3.19 over 4 points with the CEQ-E tool. The results of the subscales indicate that the professional support and the contact mother-newborn were the most valued dimensions. Well-being was not related to age, the obstetric formula, type of onset of labor, the duration of delivery and the tear during the expulsive period. Only the nationality and the type of anesthesia were related in a statistically significant way with some of the subscales of the tools used. Between the two scales of our study, there is moderate positive correlation (R = 0.557) that contributes to the criterion validity of the BMSP2 scale. CONCLUSIONS: The positive correlation between the two surveys indicates that both can be useful in cultural contexts such as the Mediterranean, in which both self-efficacy (dimension that emphasizes the CEQ-E scale developed in Sweden) and family participation are valued (dimension included in the Chilean questionary BMSP2)