Clinical management of plant food allergy in patients sensitized to lipid transfer proteins is heterogeneous: identifying the gaps.

BACKGROUND AND OBJECTIVE: Patients sensitized to lipid transfer protein (LTP) present a wide clinical variability. The lack of practical diagnostic and therapeutic guidelines complicate their management. The aim of the study was to describe the clinical approach of Spanish allergists to this pathology using a survey designed by PICO method and subsequent Delphi approach validation. METHODS: Designed survey was answered by 224 allergists (75% women; 57.1% with >20 years of professional experience). Homogeneity regarding clinical practice on the main points of LTP allergy diagnosis was observed, except for patients with suspected NSAID hypersensitivity (44.6% frequently include LTP skin testing). Oral food challenges were not frequently performed (63.6% occasionally to never), and they were generally (75.5%) used to confirm tolerance. It was common to recommend fruit skins avoidance (77.2%) and maintaining consumption of foods to which patients are sensitised but tolerant (99.1%). RESULTS: There was heterogeneity on other dietary indications, modifications due to co-factors, or traces avoidance. Peach sublingual immunotherapy (SLIT) was considered very/quite effective by 55.9% of allergists. The majority (79.5%) consider SLIT indicated in <25% of LTP allergic patients, based on severity (95.2%), frequency of reactions (99.4%), allergy to multiple food families (97.4%), and the quality of life/nutrition impairment (91.5%). There was different practice on SLIT prescription based on co-factor involvement. CONCLUSION: These data suggest that there is a need to increase evidence to reduce the clinical practice heterogeneity in the management of LTP allergy.

Diagnostic precision of local and World Health Organization definitions of symptomatic COVID-19 cases: an analysis of Mexico's capital.

OBJECTIVES: Case definitions are vital in a pandemic to effectively identify, isolate, and contact trace, particularly where testing is slow, scant, or not available. While case definitions have been developed in the COVID-19 pandemic, their diagnostic properties have not been adequately assessed. This study's objective is to determine the diagnostic properties of local and World Health Organization (WHO) COVID-19 case definitions in the large metropolitan area of Mexico City. METHODS: We calculated the diagnostic properties of five COVID-19 definitions (three of the Mexican government and two of the WHO) using open data of suspected COVID-19 cases in Mexico City from March 24th, 2020, until May 15th, 2021. RESULTS: All 2,564,782 people included in the analysis met the WHO suspected case definition (sensitivity: 100%, specificity: 0%). The WHO probable case definition was met by 1.2%, while the first and second Mexican suspected case had sensitivities of 61% and specificities of 61% and 67%, respectively. Confirmed case by epidemiological contact had a low sensitivity (32%) but slightly higher specificity (81%). CONCLUSIONS: Case definitions should maximize sensitivity, especially in a high-transmission area such as Mexico City. The WHO suspected case definition has the potential for detecting most symptomatic cases. We underline the need for routine evaluation of case definitions as new evidence arises to maximize their usefulness.

Modulation of gut immune response by probiotic fermented milk consumption to control IgE in a respiratory allergy model.

Allergies are a world increasing health issue and most treatments are oriented to alleviate symptoms. Probiotics have several health benefits including the improvement of the immune system. In previous work we found that consumption of commercial probiotic fermented milk (PFM) significantly reduced specific-immunoglobulin (Ig) E in serum and lungs by increasing specific-IgG and controlled allergic response to ovalbumin (OVA) in an adult mouse respiratory allergy model. Here we continued our study determining the mechanism triggered in the gut by the PFM ingestion that influenced the results previously reported. Five groups of BALB/c mice were assessed: normal-control, basal (drinks PFM five days without OVA sensitisation), sensitisation-control (no PFM intake), previous and continuous-PFM administration. Allergen administration: 3 OVA injections (1% in PBS) followed by aerosols exposure for 7 days. We determined total secretory-IgA and cytokines in small intestine (SI) fluid; CD11b+, CD103+, IgA+ cells and cytokine producing cells in SI tissue. In lungs we analysed co-expression of CD4/interferon (IFN)-γ or CD4/interleukin (IL)-10, IgE+ cells and IL-12 production. Results: continuous intake of PFM increased the expression of CD103 marker and decreased CD11b and pro-inflammatory cytokines. Coexpression of CD4/IFN-γ was confirmed in lungs of animals that consumed PFM continuously. This group had a lower count of IgE+ cells and a higher concentration of IL-12. The consumption of PFM reinforces the mucosal barrier by increasing IgA+ cells and induces signalling from the intestine to the lungs by increasing the expression of CD103+ dendritic cells related to regulatory mechanisms. The results found in this work together with those previously reported demonstrated that the intake of PFM induces a clear balance towards the Th1 response, preventing the Th2 allergic response by controlling the previously reported IgE level. According to our model, the intake of PFM could be a good strategy to alleviate the development of allergies.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Characteristics and outcomes of patients infected with nCoV19 requiring invasive mechanical ventilation in Argentina. / Características y resultados de los pacientes infectados con nCoV19 con requerimiento de ventilación mecánica invasiva en la Argentina.

OBJECTIVE: A novel coronavirus emerged this year as a cause of viral pneumonia. The main characteristics of the virus are rapid transmission, high contagion capacity and potential severity. The objective of this case series study is to describe the clinical characteristics of patients with confirmed coronavirus disease (COVID-19) admitted to different intensive care units in Argentina for mechanical ventilation. METHODS: A descriptive, prospective, multicenter case series study was conducted between April 1 and May 8, 2020. Data from patients older than 18 years who were admitted to the intensive care unit for mechanical ventilation for acute respiratory failure with a positive diagnosis of COVID-19 were included. RESULTS: The variables for 47 patients from 31 intensive care units were recorded: 78.7% were men (median age of 61 years), with a SAPS II score of 43 and a Charlson index score of 3. The initial ventilatory mode was volume control - continuous mandatory ventilation with a tidal volume less than 8mL/kg in 100% of cases, with a median positive end-expiratory pressure of 10.5cmH2O. At the end of the study, 29 patients died, 8 were discharged, and 10 remained hospitalized. The SAPS II score was higher among patients who died (p = 0.046). Charlson comorbidity index was associated with higher mortality (OR = 2.27, 95% CI 1.13 - 4.55, p = 0.02). CONCLUSION: Patients with COVID-19 and on mechanical ventilation in this series presented clinical variables similar to those described to date in other international reports. Our findings provide data that may predict outcomes.

OBJETIVO: El coronavirus ha emergido este año como causa de neumonía viral. Una de las principales características es su rápida transmisión y su potencial severidad. El objetivo de este estudio de serie de casos es describir las características clínicas de los pacientes con confirmación de enfermedad por coronavirus (COVID-19) admitidos en diferentes unidades de cuidados intensivos de la Argentina con requerimiento de ventilación mecánica. MÉTODOS: Estudio de serie de casos, descriptivo-prospectivo, multicéntrico realizado entre el 01 de abril y el 08 de mayo de 2020. Se incluyeron los datos de los pacientes mayores a 18 años, que ingresaron a la unidad de cuidados intensivos con requerimiento de ventilación mecánica por falla respiratoria aguda con diagnóstico positivo de COVID-19. RESULTADOS: Se registraron las variables de 47 pacientes de 31 unidades cuidados intensivos, 78.7% hombres de una mediana de edad de 61 años, con un SAPS II de 43, un índice de Charlson de 3. El modo ventilatorio inicial fue volume control - continuous mandatory ventilation con volumen corriente menor a 8mL/kg en el 100% de los casos, con una mediana de presión positiva al final de la espiración de 10,5cmH2O. A la fecha de cierre del estudio, 29 pacientes fallecieron, 8 alcanzaron el alta, y 10 pacientes continúan internados al cierre del estudio. El SAPS II fue mayor entre los fallecidos (p = 0.046). El índice de Charlson se asoció con mayor mortalidad (OR = 2,27 IC95% 1,13 - 4,55; p = 0,02). CONCLUSIÓN: Los pacientes con COVID-19 y ventilación mecánica de esta serie presentan variables clínicas similares a las descriptas a la fecha en otros reportes internacionales. Nuestros hallazgos proporcionan datos que permitirían de alguna manera predecir los resultados.

Características y resultados de los pacientes infectados con nCoV19 con requerimiento de ventilación mecánica invasiva en la Argentina / Characteristics and outcomes of patients infected with nCoV19 requiring invasive mechanical ventilation in Argentina

RESUMEN Objetivo: El coronavirus ha emergido este año como causa de neumonía viral. Una de las principales características es su rápida transmisión y su potencial severidad. El objetivo de este estudio de serie de casos es describir las características clínicas de los pacientes con confirmación de enfermedad por coronavirus (COVID-19) admitidos en diferentes unidades de cuidados intensivos de la Argentina con requerimiento de ventilación mecánica. Métodos: Estudio de serie de casos, descriptivo-prospectivo, multicéntrico realizado entre el 01 de abril y el 08 de mayo de 2020. Se incluyeron los datos de los pacientes mayores a 18 años, que ingresaron a la unidad de cuidados intensivos con requerimiento de ventilación mecánica por falla respiratoria aguda con diagnóstico positivo de COVID-19 Resultados: Se registraron las variables de 47 pacientes de 31 unidades cuidados intensivos, 78.7% hombres de una mediana de edad de 61 años, con un SAPS II de 43, un índice de Charlson de 3. El modo ventilatorio inicial fue volume control - continuous mandatory ventilation con volumen corriente menor a 8mL/kg en el 100% de los casos, con una mediana de presión positiva al final de la espiración de 10,5cmH2O. A la fecha de cierre del estudio, 29 pacientes fallecieron, 8 alcanzaron el alta, y 10 pacientes continúan internados al cierre del estudio. El SAPS II fue mayor entre los fallecidos (p = 0.046). El índice de Charlson se asoció con mayor mortalidad (OR = 2,27 IC95% 1,13 - 4,55; p = 0,02). Conclusión: Los pacientes con COVID-19 y ventilación mecánica de esta serie presentan variables clínicas similares a las descriptas a la fecha en otros reportes internacionales. Nuestros hallazgos proporcionan datos que permitirían de alguna manera predecir los resultados.

Abstract Objective: A novel coronavirus emerged this year as a cause of viral pneumonia. The main characteristics of the virus are rapid transmission, high contagion capacity and potential severity. The objective of this case series study is to describe the clinical characteristics of patients with confirmed coronavirus disease (COVID-19) admitted to different intensive care units in Argentina for mechanical ventilation. Methods: A descriptive, prospective, multicenter case series study was conducted between April 1 and May 8, 2020. Data from patients older than 18 years who were admitted to the intensive care unit for mechanical ventilation for acute respiratory failure with a positive diagnosis of COVID-19 were included. Results: The variables for 47 patients from 31 intensive care units were recorded: 78.7% were men (median age of 61 years), with a SAPS II score of 43 and a Charlson index score of 3. The initial ventilatory mode was volume control - continuous mandatory ventilation with a tidal volume less than 8mL/kg in 100% of cases, with a median positive end-expiratory pressure of 10.5cmH2O. At the end of the study, 29 patients died, 8 were discharged, and 10 remained hospitalized. The SAPS II score was higher among patients who died (p = 0.046). Charlson comorbidity index was associated with higher mortality (OR = 2.27, 95% CI 1.13 - 4.55, p = 0.02). Conclusion: Patients with COVID-19 and on mechanical ventilation in this series presented clinical variables similar to those described to date in other international reports. Our findings provide data that may predict outcomes.

Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Effect of Aspirin on the Intestinal Response to a Necrotic Enteritis Challenge.

The effect of aspirin on intestinal lesions was evaluated in birds undergoing an experimental challenge with Clostridium perfringens as part of a model for inducing subclinical necrotic enteritis (SNE). Broilers were raised on clean wood shavings and randomly assigned to three treatments: Uninfected (U), Infected (I), and Infected + Aspirin (I+A; 0.025% acetylsalicylic acid in drinking water during days 21-25). Birds in the I and I+A groups were gavaged with Eimeria maxima on day 18 and their feed was inoculated with C. perfringens (1 × 109 CFU/bird) during days 23-25. On day 26, birds were euthanatized, intestinal lesions were evaluated, and intestinal tissue was collected for qPCR assessment of genes thought to be involved in the immune response to SNE: IL-1ß, IL-10, MMP-2, and MMP-7. Birds in the I+A group had more-severe and numerous lesions compared to the I group. For all genes except MMP-2, expression was upregulated in the I group compared to the U group, but did not differ between the I and I+A groups. These results indicate that aspirin exacerbated the intestinal lesions associated with this disease. Aspirin could play a role in the development of a reliable and consistent model for the induction of necrotic enteritis under experimental settings.

Efecto de la aspirina en la respuesta intestinal a un desafío por enteritis necrótica. El efecto de la aspirina en las lesiones intestinales se evaluó en aves sometidas a un desafío experimental con Clostridium perfringens como parte de un modelo para inducir enteritis necrótica subclínica (SNE). Los pollos de engorde se criaron sobre viruta de madera limpia y se asignaron aleatoriamente a tres tratamientos: no infectado (U), infectado (I) e infectado + aspirina (I+A; ácido acetilsalicílico al 0.025% en el agua potable durante los días 21-25). A las aves de los grupos I e I+A se les administró por sonda gástrica Eimeria maxima en el día 18 y el alimento fue inoculado con C. perfringens (1×109 unidades formadoras de colonias/ ave) durante los días 23-25. En el día 26, las aves fueron sacrificadas, se evaluaron las lesiones intestinales y se recolectó tejido intestinal para la evaluación cuantitativa por PCR en tiempo real de los genes que se cree están involucrados en la respuesta inmune a la enteritis necrótica subclínica: IL-1ß, IL-10, MMP-2, y MMP-7. Las aves del grupo I+A tuvieron lesiones más graves y numerosas en comparación con el grupo I. Para todos los genes, excepto MMP-2, la expresión se regulaba positivamente en el grupo I en comparación con el grupo U pero no difería entre los grupos I e I+A. Estos resultados indican que la aspirina exacerbó las lesiones intestinales asociadas con esta enfermedad. La aspirina podría desempeñar un papel en el desarrollo de un modelo confiable y consistente para la inducción de enteritis necrótica bajo condiciones experimentales.

Objective demonstration of improvement of neurogenic bowel dysfunction in a case of spinal cord injury following stem cell therapy.

Constipation in spinal cord injury patients is a frequent complication that leads to a reduction of quality of life, extensive psychological and economic strain on patients and healthcare systems. We report a 58-year-old man with an incomplete SCI secondary to L1 vertebral fracture, presented gait disorder with neurogenic bowel and bladder dysfunction. He received 300 million autologous mesenchymal stromal cells (MSC) in the subarachnoid space by lumbar puncture. After the third administration of MSC the patient had an important improvement in almost every functional scale of spinal cord injury, especially in the Krogh's Neurogenic Bowel Dysfunction scale. Our present observation supports recent clinical findings about the benefit of autologous stem cell therapy for the improvement of bowel dysfunction in patients suffering spinal cord injury.

The cost-effectiveness of bevacizumab for the treatment of advanced ovarian cancer in Canada.

BACKGROUND: The overall survival (os) analysis of the icon7 trial demonstrated that frontline ovarian cancer patients with a high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease) benefited from the addition of bevacizumab to standard chemotherapy compared with standard chemotherapy alone. The objective of the present study was to investigate the cost-effectiveness, from a Canadian publicly funded perspective, of adding bevacizumab to frontline treatment of ovarian cancer at high risk of progression. METHODS: An area-under-the-curve, Markov-structured model was used to estimate the cost-effectiveness of the treatments. Long-term progression-free survival (pfs) and os were extracted from the icon7 trial (subgroup at high risk of relapse) and extrapolated by parametric time-to-event functions over a time horizon of 10 years. Canadian pfs health state utility values were obtained from the EQ-5D (EuroQoL Group, Rotterdam, Netherlands) questionnaires in the icon7 high-risk patient population. Canadian post-progression utility values were consistent with those for other gynecologic cancers. Cost inputs were informed by public sources. An annual 5% efficacy and cost discount rate was applied. A probabilistic sensitivity analysis and one-way sensitivity analyses were conducted. RESULTS: Ovarian cancer patients at high risk of progression receiving bevacizumab plus standard chemotherapy experienced a mean incremental quality-adjusted life year (qaly) gain of 0.374 years. At an additional cost of $35,901.54, the incremental cost-effectiveness ratio (icer) for the addition of bevacizumab to standard chemotherapy, relative to standard chemotherapy alone, was $95,942 per qaly. CONCLUSIONS: No formal health technology assessment willingness-to-pay threshold exists in Canada. However, at a threshold of $100,000 per qaly, bevacizumab in addition to chemotherapy is a cost-effective alternative for ovarian cancer patients who are at high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease). Using the $100,000 per qaly threshold in a probabilistic sensitivity analysis, it was determined that, compared with standard chemotherapy, the addition of bevacizumab to chemotherapy is cost-effective in 56% of tested scenarios.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.