The oral microbiome as a proxy for feed intake in dairy cattle.

Genetic material from rumen microorganisms can be found within the oral cavity, and hence there is potential in using the oral microbiome as a proxy of the ruminal microbiome. Feed intake (FI) influences the composition of rumen microbiota and might directly influence the oral microbiome in dairy cattle. Ruminal content samples (RS) from 29 cows were collected at the beginning of the study and also 42 d later (RS0 and RS42, respectively). Additionally, 18 oral samples were collected through buccal swabbing at d 42 (OS42) from randomly selected cows. Samples were used to characterize and compare the taxonomy and functionality of the oral microbiome using nanopore sequencing and to evaluate the feasibility of using the oral microbiome to estimate FI. Up to 186 taxonomical features were found differentially abundant (DA) between RS and OS42. Similar results were observed when comparing OS42 to RS collected on different days. Microorganisms associated with the liquid fraction of the rumen were less abundant in OS42 because these were probably swallowed after regurgitation. Up to 1,102 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were found to be DA between RS and OS42, and these results differed when comparing time of collection, but DA KEGG pathways were mainly associated with metabolism in both situations. Models based on the oral microbiome and rumen microbiome differed in their selection of microbial groups and biological pathways to predict FI. In the rumen, fiber-associated microorganisms are considered suitable indicators of FI. In contrast, biofilm formers like Gammaproteobacteria or Bacteroidia classes are deemed appropriate proxies for predicting FI from oral samples. Models from RS exhibited some predictive ability to estimate FI, but oral samples substantially outperformed them. The best lineal model to estimate FI was obtained with the relative abundance of taxonomical feature at genera level, achieving an average R2 = 0.88 within the training data, and a root mean square error of 3.46 ± 0.83 (±SD) kg of DM, as well as a Pearson correlation coefficient between observed and estimated FI of 0.48 ± 0.30 in the test data. The results from this study suggest that oral microbiome has potential to predict FI in dairy cattle, and it encourages validating this potential in other populations.

Ruminal microbiome changes across lactation in primiparous Holstein cows with varying methane intensity: Heritability assessment.

Methane is a potent greenhouse gas produced during the ruminal fermentation and is associated with a loss of feed energy. Therefore, efforts to reduce methane emissions have been ongoing in the last decades. Methane production is highly influenced by factors such as the ruminal microbiome and host genetics. Previous studies have proposed to use the ruminal microbiome to reduce long-term methane emissions, as ruminal microbiome composition is a moderately heritable trait and genetic improvement accumulates over time. Lactation stage is another important factor that might influence methane production but potential associations with the ruminal microbiome have not been evaluated previously. This study sought to examine the changes in ruminal microbiome over the lactation period of primiparous Holstein cows differing in methane intensity and estimate the heritability of the abundance of relevant microorganisms. Ruminal content samples from 349 primiparous Holstein cows with 14 - 378 d in milk were collected from May 2018 to June 2019. Methane intensity (MI) of each cow was calculated as methane concentration/milk yield. Up to 64 taxonomic features (TF) from 20 phyla had a significant differential abundance between cows with low and high MI early in lactation, 16 TF during mid lactation, and none late in lactation. Taxonomical features within the Firmicutes, Proteobacteria, Melainabacteria, Cyanobacteria, Bacteroidetes and Actinobacteria phyla were associated to low MI, whereas eukaryotic TF and those within the Euryarchaeota, Verrucomicrobia, Kiritimatiellaeota, Lentisphaerae phyla were associated to high MI. Out of the 60 TF that were found to be differentially abundant between early and late lactation in cows with low MI, 56 TF were also significant when cows with low and high MI were compared in the first third of the lactation. In general, microbes associated with low MI were more abundant early in lactation (e.g., Acidaminococcus, Aeromonas and Weimeria genera) and showed low to moderate heritabilities (0.03 to 0.33). These results suggest some potential to modulate the rumen microbiome composition through selective breeding for lower MI. Differences in the ruminal microbiome of cows with extreme MI levels likely result from variations in the ruminal physiology of these cows and were more noticeable early in lactation probably due to important interactions between the host phenotype and environmental factors associated to that period. Our results suggest that the ruminal microbiome evaluated early in lactation may be more precise for MI difference, and hence, this should be considered to optimize sampling periods to establish a reference population in genomic selection scenarios.

A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Allergy to cypress and olive pollen: Clinical phenotypes and allergen recognition.

BACKGROUND AND OBJECTIVES: Cypress and olive pollen are the most prevalent sensitizer trees in the Mediterranean area. Some patients exhibit a dual sensitization which has not been well documented yet. To identify the allergens involved in the dual cypress and olive allergy (C+O) and study the relationship between phenotype and allergen sensitization. METHODS: C+O patients were selected. Monosensitized subjects to olive or cypress were used as reference. Specific IgE to whole extracts and purified allergens from olive and cypress were performed. Immunoblotting was done to analyze IgG and IgE-binding using olive polyclonal antibodies and patients' sera, respectively. Mutual immunoblotting inhibition of olive and cypress extracts, and inhibition of cypress extract immunoblotting with olive allergens were performed. Multiple correspondence analysis and hierarchical cluster classifications were conducted to analyze the relationships between C+O clinical presentation (symptoms, seasonality) and allergen profile. RESULTS: C+O patients were clustered in 4 phenotypes. The most frequent one (58.4%) was rhinoconjunctivitis in winter (February) and spring (May), with asthma in 38% of subjects. Ole e 1 and Cup s 1 were the major allergens. Homologous proteins to Ole e 1, Ole e 9 and Ole e 11 in cypress pollen were identified and these olive allergens inhibit IgE-binding to cypress extract. CONCLUSIONS: The exclusive C+O allergy results from co-sensitization to Cup s 1 and Ole e 1, and to cross-reactivity due to Ole e 1-like, Ole e 9-like and Ole e 11-like allergens not described previously, and translates into 4 clinical phenotypes of winter and/or spring or perennial rhinoconjunctivitis with and without asthma.

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

[Patients with COPD hospitalized due to COVID-19 in Spain: a comparison between the first and second wave]. / Pacientes con EPOC hospitalizados por COVID-19 en España: comparación entre la primera y la segunda ola.

Objective: This work aimed to compare the characteristics, progress, and prognosis of patients with COPD hospitalized due to COVID-19 in Spain in the first wave with those of the second wave. Material and methods: This is an observational study of patients hospitalized in Spain with a diagnosis of COPD included in the SEMI-COVID-19 registry. The medical history, symptoms, analytical and radiological results, treatment, and progress of patients with COPD hospitalized in the first wave (from March to June 2020) versus those hospitalized in the second wave (from July to December 2020) were compared. Factors associated with poor prognosis, defined as all-cause mortality and a composite endpoint that included mortality, high-flow oxygen therapy, mechanical ventilation, and ICU admission, were analyzed. Results: Of the 21,642 patients in the SEMI-COVID-19 Registry, 6.9% were diagnosed with COPD: 1,128 (6.8%) in WAVE1 and 374 (7.7%) in WAVE2 (p = 0.04). WAVE2 patients presented less dry cough, fever and dyspnea, hypoxemia (43% vs 36%, p < 0.05), and radiological condensation (46% vs 31%, p < 0.05) than WAVE1 patients. Mortality was lower in WAVE2 (35% vs 28.6%, p = 0.01). In the total sample, mortality and the composite outcome of poor prognosis were lower among patients who received inhalation therapy. Conclusions: Patients with COPD admitted to the hospital due to COVID-19 in the second wave had less respiratory failure and less radiological involvement as well as a better prognosis. These patients should receive bronchodilator treatment if there is no contraindication for it.

SARS-CoV-2 surveillance strategy in essential workers of the Madrid City Council during the first epidemic wave in Spain, March-July 2020.

OBJECTIVES: To study prevalence of infection in essential workers of Madrid City Council by occupation, related characteristics, use of protective devices, risk perception, and main concerns about COVID-19 during lockdown. METHODS: A total of 30 231 workers were PCR tested for SARS-CoV-2 infection. Information was collected on COVID-19-related symptoms, risk factors, preventive equipment, and risk perception. The crude prevalence was calculated for infection, use of protective devices, perceived risk and main concerns. Additionally, adjusted prevalence and prevalence ratios (PR) were estimated for these variables using logistic regression models with age, gender, occupation, epidemiological week and laboratory as confounding factors. RESULTS: Overall prevalence of infection was 3.2% (95% CI 3.0% to 3.4%), being higher among policemen (4.4%) and bus drivers (4.2%), but lower among emergency healthcare personnel, firefighters, food market workers and burial services (<2%). Lower excess risk was observed in workers reporting occupational contact with COVID-19 cases only (PR=1.42; 95% CI 1.18 to 1.71) compared with household exposure only (PR=2.75; 95% CI 2.32 to 3.25). Infection was more frequent in symptomatic workers (PR=1.28; 95% CI 1.11 to 1.48), although 42% of detected infections were asymptomatic. Use of facial masks (78.7%) and disinfectants (86.3%) was common and associated with lower infection prevalence (PRmasks=0.68; 95% CI 0.58 to 0.79; PRdisinfectants=0.75; 95% CI 0.61 to 0.91). Over 50% of workers felt being at high risk of infection and worried about infecting others, yet only 2% considered quitting their work. CONCLUSIONS: This surveillance system allowed for detecting and isolating SARS-CoV-2 cases among essential workers, identifying characteristics related to infection and use of protective devices, and revealing specific needs for work-safety information and psychological support.

Association Between the Seed Storage Proteins 2S Albumin and 11S Globulin and Severe Allergic Reaction After Flaxseed Intake.

BACKGROUND: Given the increased popularity of flaxseed in meals, several cases of allergy to these seeds have been reported. Little is known about the allergens implicated in hypersensitivity reactions to flaxseed. The present study aimed to identify the allergens involved in IgE-mediated reactions in 5 patients with a clinical history of severe systemic symptoms after flaxseed consumption. METHODS: Proteins that were potential allergens with IgE-binding capacity were purified from flaxseed extract using chromatography and identified via MALDI-TOF mass spectrometry. Immunoassays were performed using the 5 allergic patients' sera tested individually and as a pool. RESULTS: Immunoblotting of the flaxseed extract revealed a low-molecular-mass protein (around 13 kDa) in 4 of the 5 patients, while a protein of approximately 55 kDa was detected in 2 patients. The proteins were identified by mass spectrometry as flaxseed 2S albumin, which is included in the WHO/IUIS allergen nomenclature as Lin u 1, and 11S globulin. Inhibition assays revealed in vitro IgE-mediated cross-reactivity between Lin u 1 and peanut and cashew nut proteins, while IgE-mediated recognition of 11S globulin by patients' sera was partially inhibited by several plant-derived sources. CONCLUSIONS: Seed storage proteins from flaxseed were involved in the development of severe symptoms in the 5 patients studied and exhibited cross-reactivity with other allergenic sources. Besides the severity of flaxseed allergy in patients sensitized to 2S albumin, this is the first time that 11S globulin has been identified as a potential allergen. Taking these data into account should ensure a more accurate diagnosis.

Der p 23 sensitisation in patients with house dust mite respiratory allergy.

Summary: Background. The sensitization profile of patients allergic to house dust mites (HDM) and its molecular diagnosis may determine treatment and evolution of the disease. The present study investigates the prevalence of Der p 23 sensitization and its relation to asthma in a population of HDM-allergic patients. Methods. We conducted a cross-sectional study of 891 patients with HDM allergy with symptoms of rhinitis and 52.1% of them with asthma. Total and specific IgE (sIgE) was measured against Dermatophagoides pteronyssinus and its molecular components (Der p 1, Der p 2 and Der p 23) and the storage mite Lepidoglyphus destructor using ImmunoCAP. Prevalence of sensitization and levels of sIgE were analysed according to asthma diagnosis and asthma severity. Results. Der p 23 was the predominant allergen in this population (83.7%) but IgE levels were lower than those of sIgE to Der p 1 and Der p 2. A good correlation was found between sIgE to Der p 23 and the other allergens. A total of 8.2% patients were monosensitized to Der p 23. Asthma was more frequent in patients with positive sIgE against Der p 23 than in patients without this sensitization (52.8% vs 42.8%, p = 0.027). A tendency to increase both total IgE and sIgE was observed in relation to the severity of asthma from intermittent mild asthma to persistent moderate asthma but a substantial decrease in total IgE and sIgE was detected in more severe asthmatics. Conclusions. Der p 23 might be a prevalent allergen in regions with high rates of HDM exposure. Even though sIgE levels against this allergen are usually low, its presence could increase the risk of asthma.

[Clinical characteristics and risk factors for mortality upon admission in patients with heart failure hospitalized due to COVID-19 in Spain]. / Características clínicas y factores de riesgo de mortalidad al ingreso en pacientes con insuficiencia cardíaca hospitalizados por COVID-19 en España.

Background: There are few studies on patients with heart failure (HF) hospitalized for COVID-19. Our aim is to describe the clinical characteristics of patients with HF hospitalized for COVID-19 and identify risk factors for in-hospital mortality upon admission. Methods: We conducted a retrospective, multicenter study in patients with HF hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A multivariate logistic regression analysis was performed to identify admission risk factors associated with in-hospital mortality. Results: A total of 1,718 patients were analyzed (56.5% men; median age 81.4 years). The overall case fatality rate was 47.6% (n=819). The independent risk factors at admission for in-hospital mortality were: age (adjusted odds ratio [AOR]: 1.03; 95% confidence interval [95%CI]: 1.02-1.05; p< .001); severe dependence (AOR: 1.62; 95%CI: 1.19-2.20; p=.002); tachycardia (AOR: 1.01; 95%CI: 1.00-1.01; p=.004); and high C-reactive protein (AOR: 1.004; 95%CI:1.002-1.004; p< .001), LDH (AOR: 1.001; 95%CI: 1.001-1.002; p< .001), and serum creatinine levels (AOR: 1.35; 95%CI: 1.18-1.54; p< .001). Conclusions: Patients with HF hospitalized for COVID-19 have a high in-hospital mortality rate. Some simple clinical and laboratory tests can help to identify patients with a worse prognosis.

Cytokines and growth factors in a biologic product obtained from patients' urine as immune-modulators to treat autoimmune and allergic diseases.

At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.

Efficacy and Safety of Up-dosing Antihistamines in Chronic Spontaneous Urticaria: A Systematic Review of the Literature.

BACKGROUND AND OBJECTIVES: According to current guidelines, oral antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU). Up-dosing antihistamines to 4-fold the licensed dose is recommended if control is not achieved. Such indications are based mainly on expert opinion. Objectives: To critically review and analyze clinical evidence on the efficacy and safety of higher-than-licensed dosage of second-generation oral antihistamines in the treatment of CSU. MATERIAL AND METHODS: A systematic literature review was performed following a sensitive search strategy. All articles published in PubMed, EMBASE, and the Cochrane Library between 1961 and October 2018 were examined. Publications with CSU patients prescribed secondgeneration antihistamines in monotherapy compared with placebo, licensed dosages, and/or higher dosages were included. Articles were evaluated by peer reviewers. Quality was evaluated using the Jadad and Oxford scores. RESULTS: We identified 337 articles, of which 14 were included in the final evaluation (fexofenadine, 6; cetirizine, 2; levocetirizine and desloratadine, 1; levocetirizine, 1; rupatadine, 2; ebastine, 1; and bilastine, 1). Only 5 studies were placebo-controlled. The number of patients included ranged from 20 to 439. The observation lapse was ≤16 weeks. High fexofenadine doses produced a significant dosedependent response and controlled urticaria in most patients. Cetirizine, levocetirizine, rupatadine, and bilastine were more effective in up-dosing. The most frequent adverse events were headache and drowsiness. CONCLUSION: The low quality and heterogeneity of the articles reviewed made it impossible to reach robust conclusions and reveal the need for large-scale randomized clinical trials.

ARADyAL: The Spanish Multidisciplinary Research Network for Allergic Diseases.

Thematic cooperative health research networks (RETICS) are organizational structures promoted by the Instituto de Salud Carlos III of the Spanish Ministry of Science with the objective of carrying out cooperative research projects addressing challenges of general interest for society as a whole in the field of health care. The RETICS of Asthma, Adverse Drug Reactions, and Allergy (ARADyAL) received funding in 2016 for a 5-year program (2017-2021). ARADyAL integrates basic and clinical research in the areas of allergy, immunology, genetics, nanomedicine, pharmacology, and chemistry, with special interest in research on new biomarkers and the design and evaluation of new interventions for allergic patients with severe phenotypes. The consortium comprises 28 groups across Spain, including 171 clinical and basic researchers, 17 clinical groups that cover more than 10 000 000 patients of all ages from urban and rural areas and 11 basic groups active mostly at universities and research institutes. ARADyAL has proposed a research program organized into 3 different areas focusing on precision medicine, as follows: Program 1, Mechanisms and prediction of adverse drug reactions and allergic diseases; Program 2, Toward a precise diagnosis of allergic diseases; and Program 3, Predicting interventions in allergic diseases. There is also 1 common program dedicated to training. The network has a Steering Committee and an External Advisory Scientific Committee, which advise the global network coordinator, who has recognized expertise in the field. ARADyAL is a unique meeting point for clinicians and basic scientists who are already working in allergy.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

IL-1-dependent electrophysiological changes and cardiac neural remodeling in a mouse model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. In addition to coronary artery abnormalities, aneurysms and myocarditis, acute KD is also associated with echocardiogram (ECG) abnormalities in 40-80% of patients. Here, we show that these ECG changes are recapitulated in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. LCWE-injected mice developed elevated heart rate and decreased R wave amplitude, with significant differences in prolonged ventricular repolarization. LCWE-injected mice developed cardiac ganglion inflammation, that may affect the impulse-conducting system in the myocardium. Furthermore, serum nerve growth factor (NGF) was significantly elevated in LCWE-injected mice, similar to children with KD vasculitis, associated with increased neural remodeling of the myocardium. ECG abnormalities were prevented by blocking interleukin (IL)-1 signaling with anakinra, and the increase in serum NGF and cardiac neural remodeling were similarly blocked in Il1r1-/- mice and in wild-type mice treated with anakinra. Thus, similar to clinical KD, the LCWE-induced KD vasculitis mouse model also exhibits electrophysiological abnormalities and cardiac neuronal remodeling, and these changes can be prevented by blocking IL-1 signaling. These data support the acceleration of anti-IL-1 therapy trials to benefit KD patients.

Experimental transmission of Caligus rogercresseyi between two different fish species.

Caligus rogercresseyi is the dominant sea louse parasite affecting the salmon and trout industry in southern Chile. This parasite has a wide range of native and endemic fish hosts. The Patagonian blenny Eleginops maclovinus, which is parasitized mostly by the caligid species Lepeophtheirus spp. and C. rogercresseyi, is presumably responsible for the transmission of C. rogercresseyi to salmonids. The aim of this study was to characterize the transmission of parasites between different fish species and parasite cohort development under laboratory conditions. Parasite abundances and intensities were quantified. Transmission of parasites from Patagonian blenny to Atlantic salmon Salmo salar was lower (~9%, mainly corresponding to C. rogercresseyi) than from salmon to Patagonian blenny (14.7-26.9%, where only C. rogercresseyi were observed). This suggests that the transmission of C. rogercresseyi from salmon individuals is higher than the transmission from a native fish. Parasite cohorts developed successfully on both fish species, but apparently under different developmental rates. Water temperature, oxygen, and juvenile abundances were the variables that better explained cohort development success and variation in C. rogercresseyi adult abundances over time.

[Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry]. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥ 80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

IL-1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis.

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

OBJECTIVE: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. METHODS: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. RESULTS: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. CONCLUSIONS: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.