Transition between subcutaneous and sublingual allergen immunotherapy: Recommendations of the Brazilian Association of Allergy and Immunology (ASBAI).

The use of allergen immunotherapy (AIT) in Brazil has specific regional conditions owing to the pattern of allergen sensitization, as well as to genetic, socioeconomic, and cultural characteristics. This review article aims to discuss the clinical practice of AIT by the subcutaneous or sublingual route in Brazil, addressing the possibilities of transition between these forms of administration. A systematic review using the PubMed and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. Knowledge of the mechanism of action of subcutaneous immunotherapy and sublingual immunotherapy, together with Brazilian real-life experience, allowed us to establish recommendations regarding switching routes of AIT administration in selected cases. Careful analysis of each clinical situation is necessary to perform the transition between subcutaneous and sublingual allergen immunotherapy.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

Subcutaneous allergen immunotherapy for asthma: A randomized, double-blind, placebo-controlled study with a standardized Blomia tropicalis vaccine.

BACKGROUND: Sensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. OBJECTIVE: To assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. METHODS: A double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). RESULTS: The 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26-61) of placebo values, whereas medication was 34.5% (22.4%-63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. CONCLUSIONS: Subcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).

Proteomic identification of allergenic proteins in red oak (Quercus rubra) pollen.

BACKGROUND: Red oak pollen is an important cause of allergic respiratory disease and it is widely distributed in North America and central Europe. To date, however, red oak pollen allergens have not been identified. Here, we describe the allergenic protein profile from red oak pollen. METHODS: Total proteins were extracted from red oak pollen using a modified phenolic extraction method, and, subsequently, proteins were separated by two-dimensional gel electrophoresis (2DE) for both total protein stain (Coomassie Blue) and immunoblotting. A pool of 8 sera from red oak sensitive patients was used to analyze blotted proteins. Protein spots were analyzed by Mass Spectrometry. RESULTS: Electrophoretic pattern of total soluble proteins showed higher intensity bands in the regions of 26-40 and 47-52 kDa. Two dimensional immunoblots using pool sera from patients revealed four allergenic proteins spots with molecular masses in the range from 50 to 55 kDa. Mass spectrometry analysis identified 8 proteins including Enolase 1 and Enolase 1 chloroplastic, Xylose isomerase (X1 isoform), mitochondrial Aldehyde dehydrogenase, UTP-Glusose-1-phosphate uridylyltransferase, Betaxylosidase/alpha-l-arabinofuranosidase and alpha- and beta subunits of ATP synthase. CONCLUSIONS: This study has identified for first time 8 IgE binding proteins from red oak pollen. These findings will pave the way towards the development of new diagnostic and therapeutic modalities for red oak allergy.

Epidemiológica del ataque cerebro vascular en un hospital universitario / Epidemiological of cerebrovascular attack in a university hospital / Epidemiologia do ataque cerebrovascular em hospital universitário

Resumen: Introducción: El ataque cerebro vascular es una enfermedad prevalente en nuestro medio con elevada morbimortalidad. El Hospital Pasteur es un centro de tercer nivel, que asiste un elevado número de pacientes con esta patología. Conocer los datos epidemiológicos de esta afección permitirá desarrollar medidas de promoción de salud y prevención primaria. Identificar la forma de presentación clínica y los algoritmos de estudio, permitirán un adecuado diagnóstico, tratamiento precoz y desarrollo de medidas de prevención secundaria. Objetivos: Conocer las características sociodemográficas de la población con diagnóstico de ataque cerebro vascular o accidente isquémico transitorio asistidas en las salas de medicina del Hospital Pasteur, los factores de riesgo asociados, las formas de presentación clínica y precisar si se cumplió con el algoritmo diagnóstico propuesto. Métodos y procedimiento: Estudio descriptivo observacional y transversal realizado en el Hospital Pasteur. La población de estudio fueron pacientes adultos ingresados en sala de medicina con diagnóstico de ataque cerebro vascular o accidente isquémico transitorio que presentaron el evento durante su internación, en el periodo comprendido entre Julio y Setiembre de 2018. Resultados y discusión: Se recabaron datos de 29 pacientes, 20 de sexo femenino. La media de edad fue de 70.34 años. La naturaleza isquémica fue la más prevalente. Los factores de riesgo cardiovascular más frecuentes fueron HTA, sedentarismo, dislipemia y tabaquismo. La principal forma de presentación fue síndrome piramidal. Se cumplió con el algoritmo diagnostico en todos los pacientes. Conclusión: Conocer los factores de riesgo, naturaleza y forma de presentación clínica permite elaborar estrategias de prevención primaria y secundaria para el abordaje integral de estos pacientes, intentando así reducir la incidencia y secuelas de esta enfermedad.

Abstract: Introduction: Acute ischemic stroke is a prevalent condition in our working environment, with high morbility and mortality. Hospital Pasteur is a tertiary level institution, which assists an elevated number of patients with acute ischemic stroke. Getting to know its epidemiologic characteristics will enable the development of health promotion and primary prevention measures. Identifying its clinical presentation form and applying validated study algorithms will allow for a proper diagnosis, early treatment and development of secondary prevention measures. Objectives: To study the sociodemographic characteristics of patients diagnosed with acute ischemic stroke or transient ischemic attack assisted in Hospital Pasteur´s Internal Medicine wards, their associated risk factors, clinical presentation and to determine whether the proposed study algorithm was followed. Methodology and procedure: This is a descriptive, observational and transversal study which took place at Hospital Pasteur. The population consisted of adult patients admitted to Internal Medicine wards with the diagnosis of acute ischemic stroke, transient ischemic attack or who presented the event during their stay, between the months of July and September 2018. Results and discussion: The data of 29 patientes was obtained; 20 were female. The mean age was 70.34 years. Ischemic nature was the most prevalent. The most frequent risk factors were arterial hypertension, sedentary lifestyle, dyslipidemia and smoking. Pyramidal syndrome was the most common clinical presentation. A study algorithm was followed in all patients. Conclusion: Getting to know the risk factors, nature and clinical presentation form of AIS and TIA allows for the creation of primary and secondary prevention strategies for the comprehensive approach of these patients, therefore intending to reduce this disease´s incidence and its terrible consequences.

Resumo: Introdução: O ataque cerebrovascular é uma doença prevalente em nosso meio, com alta morbimortalidade. O Hospital Pasteur é um centro de terceiro nível, que auxilia um grande número de pacientes com essa patologia. Conhecer os dados epidemiológicos dessa condição permitirá o desenvolvimento de ações de promoção da saúde e prevenção primária. Identificar a forma de apresentação clínica e os algoritmos do estudo permitirá um diagnóstico adequado, tratamento precoce e desenvolvimento de medidas de prevenção secundária. Objetivos: Conhecer as características sociodemográficas da população com diagnóstico de ataque cerebrovascular ou ataque isquêmico transitório assistido nas salas médicas do Hospital Pasteur, os fatores de risco associados, as formas de apresentação clínica e determinar se o algoritmo de diagnóstico proposto foi atendido. Métodos e procedimentos: Estudo observacional e transversal descritivo realizado no Hospital Pasteur. A população do estudo foi de pacientes adultos admitidos na enfermaria com diagnóstico de ataque cerebrovascular, ataque isquêmico transitório que apresentaram o evento durante sua internação, no período entre julho e setembro de 2018. Resultados e discussão: Os dados foram coletados de 29 pacientes, sendo 20 do sexo feminino. A idade média foi de 70,34 anos, sendo a natureza isquêmica a mais prevalente. Os fatores de risco cardiovascular mais frequentes foram hipertensão arterial, sedentarismo, dislipidemia e tabagismo. A principal forma de apresentação foi a síndrome piramidal. O algoritmo de diagnóstico foi preenchido em todos os pacientes. Conclusão: Conhecer os fatores de risco, natureza e forma de apresentação clínica permite desenvolver estratégias de prevenção primária e secundária para abordagem abrangente desses pacientes, buscando reduzir a incidência e sequelas da doença.

Biomonitoring levels and trends of PAHs and synthetic musks associated with land use in urban environments.

Polycyclic aromatic hydrocarbons (PAHs) are some of the most studied organic compounds in urban environments, due to their known adverse effects on human health and persistence in environmental matrices. During the last decade, new groups of organic compounds with an intensive use worldwide such as synthetic musks have been raising the interest of the scientific community given their toxicity and health effects. However, literature is still scarce in studies dealing with their concentration in the environment, especially in developing countries, where they are even more rare or non-existing at all. We employed leaves of Ligustrum lucidum to assess the concentrations of PAHs and synthetic musks in different land use areas in Cordoba city, therefore contributing with environmental information in Argentina. We found higher levels of PAHs in urban and industrial areas than in the peri-urban sampling sites, naphthalene being one of the dominant PAHs in all sampling areas. Regarding synthetic musk fragrances, polycyclic musks were the most contributing compounds and the highest levels found in industrial areas as well. A high environmental risk could be expected due to the frequent occurrence of galaxolide in addition to the high hazardous potential of phantolide, which was present in 50% of the samples. The results of the present study indicate that leaves of an urban ubiquitous tree can be used to assess the spatial behavior of both "classic" and "emerging" organic pollutants, allowing an assessment of urban air quality in areas where common air sampling devices are unavailable.

Unidad de ACV en el Hospital de Clínicas: comportamiento clínico-epidemiológico de los pacientes con ACV (2007-2012) / Stroke Unit at the Hospital de Clínicas: clinical-epidemiological behavior in patients with stroke (2007-2012)

Introducción: El ataque cerebrovascular (ACV) es una importante causa de mortalidad, discapacidad y demencia en el mundo y en nuestro país. Provoca un gran impacto económico ya sea por gastos directos o indirectos. Objetivos: Describir aspectos clínicos, factores de riesgo e indicadores que permiten un adecuado manejo del ACV en su tratamiento agudo. Material y Métodos: Se realizó un estudio descriptivo y prospectivo de los ACV ingresados en el Hospital de Clínicas, entre 2007 y 2012 aplicando un protocolo con escalas clínicas, etiopatogénicas y funcionales, con test estadísticos adecuados. Resultados: Se protocolizaron 784 pacientes: 75% infartos, 16% hemorragias y 9% AIT. La HTA fue el factor de riesgo más frecuente. Un tercio llegó a puerta antes de las 4,5 h. En infartos y AIT se disminuyeron los días de internación y se mejoró la funcionalidad a 6 meses. Conclusiones: La formación de equipos entrenados en el diagnóstico y tratamiento del ACV disminuyeron el tiempo de internación y mejoraron la funcionalidad de estos pacientes.

Introduction: The cerebrospinal fluid (CSF) fistula is defined as the abnormal leak of fluid from the skull to outside the body through an osteomeningeal gap, which allows the passage of organisms to the intra-cranial space, with the risk of infection, potentially life-threatening. Divided as traumatic and non-traumatic, the condition is relatively common, and poses great challenges to neurosurgeons. Objective: to present the first case of post-traumatic CSF fistula in Uruguay, assessed with cistern MRI with diagnostic purposes. Case report: the case described is that of a patient that received treatment at the University Hospital (Hospital de Clínicas). The case is used to illustrate the condition and review the latest controversial issues involved in the algorithms for the diagnosis and therapy of the condition. Discussion: the main controversial issues found included the following: when to start prophylactic antibiotic (ATB) therapy following diagnosis; imaging tests requested for diagnosis, and type of therapy prescribed. Conclusions: The review of literature leads us to conclude that a correct diagnosis requires the routine use of CT and MRI; if doubts persist, cistern MRI, endoscopy, or cistern CT are indicated. With regards the therapeutic algorithm, we conclude that therapy should be conservative, applying medical therapy for two to four weeks; surgery will be prescribed if the fistula persists after that. Antibiotic therapy is an option and not a recommendation.

Manejo agudo do AVC isquêmico: da emergência à alta hospitalar / Acute stroke management: from the emergency room to discharge

O AVC é uma causa muito frequente de morbimortalidade na população mundial, representando um verdadeiro desafio à prática médica atualmente. Todo médico deve ter conhecimento sobre o manejo inicial desta condição, o que pode mudar drasticamente o rumo da história natural da doença.

Stoke is a very common cause of mortality and morbidity in the population worldwide, representing a true challenge in medical practice nowadays. Every physician must know how to approach this condition, something that can dramatically change the natural course of the disease.

Proteomic analysis during ontogenesis of secondary xylem in maritime pine.

Secondary xylem (wood) is formed through an intricate biological process that results in a highly variable final product. Studies have focused on understanding the molecular events for wood formation in conifers. In this process environmental, ontogenic and genetic factors influence variation in wood characteristics, including anatomical, chemical and physical properties. The main objective of this study was to analyse the ageing (ontogenic) effect on protein accumulation in wood-forming tissues along a cambial age (CA) gradient, ranging from juvenile wood (JW) sampled at the top of the tree, to mature wood (MW) sampled at the bottom of the tree. A total of 62 proteins whose accumulation varied by at least 1.5-fold according to CA were selected and identified by ESI-MS/MS; 30 of these were more abundant in MW and 32 were more abundant in JW. Consistent with earlier findings, our results show that JW is a tissue characterized by a high energy demand with the accumulation of gene products involved in energy, protein fate and cellular transport, while proteins identified in MW (heat shock response, oxygen and radical detoxification, and the S-adenosyl methionine cycle) support the idea that this tissue undergoes extended cell-wall thickening and a delay of programmed cell death.