Oral immunotherapy in severe cow's milk allergic patients treated with omalizumab: Real life survey from a Spanish registry.

BACKGROUND: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting. METHODS: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab. RESULTS: Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kUA /L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to ≥6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to ≥6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% ≥6000 mg). CONCLUSION: Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored.

Perceived barriers to implementing screening and brief intervention for alcohol consumption by adolescents in hospital emergency department in Spain. / Barreras percibidas contra la implementación en los servicios de urgencias hospitalarios en España de un protocolo de cribado de consumo de alcohol e intervención breve en adolescentes.

BACKGROUND: Screening for alcohol consumption in adolescents is widely justified in the health care field because of the particular vulnerability of this population, which starts drinking alcohol at a very early age and frequently consumes high levels of the same. Hospital emergency departments (ED) could be a good venue to manage early detection and carry out brief intervention (BI) programmes. OBJECTIVES: The aim of this study was to identify perceived barriers for medical staff of three hospitals in Spain to successfully implement a protocol for alcohol detection and BI for minors in the ED. METHODS: Exploratory qualitative analysis using focus groups with semi-structured, flexible and open-ended questions to explore beliefs, attitudes, and barriers perceived by professionals to screening alcohol consumption and implementing BI in adolescents attended at the ED. RESULTS: The main perceived barriers by health professionals were lack of time, work overload, mistrust, lack of validated and simple screening tools, lack of training/awareness and legal concerns about informed consent and confidentiality. CONCLUSIONS: Barriers to screening and intervention in ED are similar to those described previously. It is necessary to improve organization of time allocated for medical consultations, avoid limiting ED resources, motivate staff and provide appropriate training.

Introducción: El cribado de consumo de alcohol en menores está ampliamente justificado en el ámbito sanitario por la evidencia epidemiológica de consumo y por la especial vulnerabilidad de este colectivo, que además se inicia a edades muy tempranas e ingiere grandes cantidades. Los servicios de urgencias (ED) podrían ser un entorno donde realizar la detección precoz e implementar una intervención breve (IB) por parte de los profesionales. Objetivo: El objetivo de este estudio es conocer las barreras percibidas por los profesionales sanitarios para implantar con éxito en los servicios de urgencias hospitalarios un protocolo de detección e IB en menores. Material y métodos: Análisis cualitativo exploratorio mediante grupos focales con preguntas semiestructuradas, flexibles y abiertas para conocer las creencias, actitudes y barreras percibidas por los profesionales de los centros donde se desarrollará un proyecto de cribado de consumo de alcohol e IB en adolescentes que acuden a Urgencias. Resultados: Las principales barreras percibidas fueron falta de tiempo, sobrecarga de trabajo, desconfianza en la sinceridad de las respuestas, necesidad de protocolos estandarizados de trabajo, desconocimiento de herramientas de cribado validadas y sencillas, falta de entrenamiento/concienciación y dudas médico-legales sobre el consentimiento informado y la confidencialidad del menor. Conclusiones: Las barreras percibidas para implementar la herramienta de cribado e IB son similares a las descritas por otros autores y sería necesario mejorar la organización de los circuitos asistenciales, no limitar los recursos dedicados a la atención en urgencias y favorecer la motivación y la formación de los profesionales.

Seeking potential anticonvulsant agents that target GABAA receptors using experimental and theoretical procedures.

The aim of this study was to identify compounds that possess anticonvulsant activity by using a pentylenetetrazol (PTZ)-induced seizure model. Theoretical studies of a set of ligands, explored the binding affinities of the ligands for the GABA(A) receptor (GABA(A)R), including some benzodiazepines. The ligands satisfy the Lipinski rules and contain a pharmacophore core that has been previously reported to be a GABA(A)R activator. To select the ligands with the best physicochemical properties, all of the compounds were analyzed by quantum mechanics and the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital were determined. Docking calculations between the ligands and the GABA(A)R were used to identify the complexes with the highest Gibbs binding energies. The identified compound D1 (dibenzo(b,f)(1,4)diazocine-6,11(5H,12H)-dione) was synthesized, experimentally tested, and the GABA(A)R-D1 complex was submitted to 12-ns-long molecular dynamics (MD) simulations to corroborate the binding conformation obtained by docking techniques. MD simulations were also used to analyze the decomposition of the Gibbs binding energy of the residues involved in the stabilization of the complex. To validate our theoretical results, molecular docking and MD simulations were also performed for three reference compounds that are currently in commercial use: clonazepam (CLZ), zolpidem and eszopiclone. The theoretical results show that the GABA(A)R-D1, and GABA(A)R-CLZ complexes bind to the benzodiazepine binding site, share a similar map of binding residues, and have similar Gibbs binding energies and entropic components. Experimental studies using a PTZ-induced seizure model showed that D1 possesses similar activity to CLZ, which corroborates the predicted binding free energy identified by theoretical calculations.

C-Phycocyanin: A Phycobiliprotein from Spirulina with Metabolic Syndrome and Oxidative Stress Effects.

Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC.

[Reproducibilidad clínica de reacciones de hipersensibilidad a fármacos en pruebas de exposición controlada].

Objective: To assess the reproducibility of symptoms in drug challenge tests. Methods: The study included patients with positive cutaneous or challenge test throughout 2019. For each patient, clinical suspicion according to Karch-Lasagna algorithm was registered. Primary outcome was the reproducibility of symptoms in the provocation tests using a paired analysis of data with McNemar test. Results: Eighty-nine patients were included, 16 of them presented more than one positive test. Thirty were skin tests positive and 75 reacted to provocation tests. Eighty nine percent of patients who reacted in challenge test were probably or possibly reactors according to Karch-Lasagna scale. Symptoms of initial reaction did not differ from those triggered in challenge tests. Conclusions: Karch-Lasagna scale is useful in predicting the response to drug provocation tests. In most of the positive studies, results were suggested by clinical history and no differences were found between symptoms triggered in challenge test and that referred to in the previous reaction.

Objetivo: Evaluar la reproducibilidad de los síntomas en pruebas de exposición con fármacos. Métodos: Estudio retrospectivo, efectuado en pacientes con prueba cutánea o exposición positiva, atendidos en 2019. De cada paciente se registró la sospecha clínica según el algoritmo de Karch-Lasagna. El resultado principal fue la reproducibilidad de síntomas en las pruebas de exposición, mediante el análisis de datos emparejado con prueba de McNemar. Resultados: Se incluyeron 89 pacientes, y de estos 16 reportaron varias pruebas positivas. Se obtuvieron 30 pruebas cutáneas y 75 de exposición positivas. En el 89% de las pruebas de exposición positivas, las reacciones iniciales se clasificaron en probables o posibles, según la escala de Karch-Lasagna. Los síntomas reportados en la reacción inicial no difirieron de los de las pruebas de exposición. Conclusiones: La escala de Karch-Lasagna es un método útil para predecir la respuesta en las pruebas de exposición con fármacos. En la mayor parte de las pruebas positivas, los resultados fueron sugeridos por la historia clínica, sin diferencias entre la manifestación de síntomas en la prueba de exposición versus los referidos en la reacción inicial.

Combined LTP Sublingual and Oral Immunotherapy in LTP Syndrome: Efficacy and Safety.

INTRODUCTION: SLIT for the treatment of plant food allergies has been demonstrated to be safe but less effective than OIT, but the latter is associated with more adverse reactions. The aim of the study was to evaluate the efficacy and safety of a new protocol starting with SLIT-peach followed by OIT with commercial peach juice in patients with LTP syndrome. METHODS: This was a prospective, noncontrolled, open study on patients with LTP syndrome who are not sensitized to storage proteins. SLIT peach ALK was followed by OIT with Granini® peach juice after 40 days of the SLIT maintenance phase. At home, the Granini® juice dose was progressively increased during the 42 days until reaching 200 ml. After achieving the maximum dose, an open oral food challenge was carried out with the food that had caused the most severe reaction. If negative, the patient was instructed to progressively introduce the foods that were avoided before starting immunotherapy at home. Patients were reviewed 1 month later. The quality-of-life questionnaire FAQLQ-AF was completed at the beginning of the study and one month after the final challenge. RESULTS: Forty-five patients were included, most of them with LTP anaphylaxis. Peach SLIT was well tolerated in 80.5%, and OIT with Granini® was well tolerated in 85%, with no severe adverse reactions. The final provocation was successful in 39/45 (86.6%). One month after the final provocation, 42/45 (93.3%) patients had no dietary restrictions. FAQLA-AF was significantly reduced. CONCLUSIONS: This combination of peach SLIT and OIT with commercial peach juice provides a new, fast, effective, and safe immunotherapy option for selected patients with LTP syndrome who are not allergic to storage proteins, improving their quality of life. This study suggests that cross-desensitization relative to the nsLTPs of several plant foods can be achieved by using Prup3.

Flaxseed Oil (Linum usitatissimum) Prevents Cognitive and Motor Damage in Rats with Hyperammonemia.

Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.

Protective Effect of the Phycobiliproteins from Arthrospira maxima on Indomethacin-Induced Gastric Ulcer in a Rat Model.

Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.

Effects of Spirulina maxima on a Model of Sexual Dysfunction in Streptozotocin-Induced Diabetic Male Rats.

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.

[Contact dermatitis caused by diagnostic devices and surgical orthopedic treatment]. / Dermatitis de contacto causada por dispositivos de diagnóstico y tratamiento quirúrgico ortopédico.

BACKGROUND: Acrylates are plastic materials that are formed by the polymerization of monomers that are derived from acrylic or methacrylic acid; they have a wide range of applications, and they are increasingly used in medicine. CASE REPORT: We are reporting two clinical cases of contact dermatitis in the hospital environment; the first one is about a nurse (occupational exposure) and, the second one, about a patient who experienced contact dermatitis after a diagnostic procedure was performed. CONCLUSION: New sources of acrylates are identified every year due to the multiple uses of these synthetic resins; these materials are included in medical devices, both for orthopedic diagnosis or follow-up (telemetry, electrodes of electroencephalographs) and treatment (bone cement), as well as for surgery.

Antecedentes: Los acrilatos son materiales plásticos que se forman por la polimerización de monómeros derivados del ácido acrílico o metacrílico; tienen una amplia gama de aplicaciones y cada vez son más usados en el campo de la medicina. Casos clínicos: Presentamos dos casos clínicos de dermatitis de contacto en el entorno hospitalario: el primero se trata de una enfermera (exposición ocupacional) y el segundo, de un paciente a quien se le realizó un procedimiento diagnóstico. Conclusión: Cada año se identifican nuevas fuentes de acrilatos debido a las múltiples utilidades de estas resinas sintéticas; estos materiales se incluyen en dispositivos médicos, tanto para el diagnóstico o seguimiento (telemetría, electrodos de electroencefalógrafos) como para el tratamiento (cemento óseo) y cirugía ortopédica.

Provocation Tests in Nonimmediate Hypersensitivity Reactions to ß-Lactam Antibiotics in Children: Are Extended Challenges Needed?

BACKGROUND: ß-Lactam antibiotics are the most common trigger of reactions in children with most of them being nonimmediate (85.5%), but proven allergy after the allergological workup is between 7% and 10%. There is no agreement on how to perform the provocation tests in these types of hypersensitivity reactions. OBJECTIVE: To determine whether or not repeated doses of the ß-lactams are required to reproduce a nonimmediate reaction in children. METHODS: This is a retrospective observational study. We included children under 14 years who were referred for a nonimmediate reaction to ß-lactams. All patients underwent a 1-day hospital provocation and were kept under observation at home during the following days for at least the time elapsed between the first dose and the symptoms of the index reaction. If no reaction was triggered, the patient resumed the provocation at home with 2 daily therapeutic doses for an equal of interval time. RESULTS: Ninety-seven patients were included in the study. A positive reaction was recorded in 14 of them (14.4%). The short hospital provocation triggered 3 immediate reactions and 8 delayed reactions. The home rechallenge developed 1 immediate reaction and 2 delayed reactions. CONCLUSIONS: Nonimmediate reactions to ß-lactams in children may be triggered with a 1-day provocation test. We suggest to perform a 1-day provocation test followed by an observational period of at least the time interval of the index reaction. If this challenge is negative, an extended home provocation could subsequently be carried out.